Explore a selection of our essential drug information below, or:
Identification
- Summary
Pexidartinib is an antitumor agent that is used for the treatment of rare disease tenosynovial giant cell tumors (TGCT) by inhibiting colony-stimulating factor 1 and its receptor.
- Brand Names
- Turalio
- Generic Name
- Pexidartinib
- DrugBank Accession Number
- DB12978
- Background
Pexidartinib is a selective tyrosine kinase inhibitor that works by inhibiting the colony-stimulating factor (CSF1)/CSF1 receptor pathway. Pexidartinib was originally developed by Daiichi Sankyo, Inc. and it was approved by the FDA in August 2019 as the first systemic therapy for adult patients with symptomatic tenosynovial giant cell tumor.11 Tenosynovial giant cell tumor is a rare form of non-malignant tumor that causes the synovium and tendon sheaths to thicken and overgrow, leading to damage in surrounding joint tissue.1,11 Debilitating symptoms often follow with tenosynovial giant cell tumors, along with a risk of significant functional limitations and a reduced quality of life in patients.11
While surgical resection is a current standard of care for tenosynovial giant cell tumor, there are tumor types where surgeries are deemed clinically ineffective with a high risk of lifetime recurrence.10 Pexidartinib works by blocking the immune responses that are activated in tenosynovial giant cell tumors. In clinical trials, pexidartinib was shown to promote improvements in patient symptoms and functional outcomes in TGCT.2 Pexidartinib is available in oral formulations and it is commonly marketed as Turalio.11
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Pexidartinib (DB12978)
- Weight
- Average: 417.82
Monoisotopic: 417.0968077 - Chemical Formula
- C20H15ClF3N5
- Synonyms
- Pexidartinib
- External IDs
- CML-261
- PLX-3397
- PLX3397
Pharmacology
- Indication
Pexidartinib is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery.9
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Symptomatic tenosynovial giant cell tumor •••••••••••• ••••• •••••••••••• •••••••••• •••••••••••• •• •••••••• •••••••••• •••••••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Pexidartinib works by suppressing the growth of tenosynovial giant cell tumors. In clinical trials comprising of patients with symptomatic tenosynovial giant cell tumor, pexidartinib had a higher overall response rate, characterized by improved patient symptoms and functional outcomes, compared to placebo.2 Pexidartinib works by inhibiting the activation and signaling of tumor-permissive cytokines and receptor tyrosine kinases that play a central role in tumor cell proliferation and survival.3 Taking pexidartinib with a high-fat meal may increase the incidence and severity of adverse reactions, including hepatotoxicity.12
- Mechanism of action
Tenosynovial giant cell tumor is a rare, non-malignant neoplasm that causes abnormal growth and damage to the synovium, bursae, or tendon sheaths.11 Recruitment of immune cells, specifically macrophages, is closely associated with the tumor mass formation in tenosynovial giant cell tumors. 1 Macrophages drive tumor-promoting inflammation 7 and play a central role in every stage of tumor progression.6 As the most abundant immune cells in the tumor microenvironment of solid tumors, macrophages promote processes that enhance tumor survival, such as angiogenesis, tumor cell invasion, and intravasation at the primary site.6 They also modulate the immune response to tumors to inhibit tumor clearance and directly engage with tumor cells to activate pro-survival signaling pathways.8
The recruitment, proliferation, and irreversible differentiation of macrophages are regulated by colony-stimulating factor-1 (CSF-1),3,5 which is a cytokine that is often translocated and highly expressed in tenosynovial giant cell tumors.8 Elevated expression of CSF-1 and CSF-1 receptor (CSF1R) has also been implicated in various models of malignant cancers and tumors.4 Pexidartinib targets the CSF1/CSF1R pathway as a selective CSF1R inhibitor. It stimulates the autoinhibited state of the CSF1R by interacting with the juxtamembrane region of CSF1R, which is responsible for folding and inactivation of the kinase domain, and preventing the binding of CSF1 and ATP to the region.1 Without the binding of CSF1 to the receptor, CSF1R cannot undergo ligand-induced autophosphorylation.9 By inhibiting the CSF1R signaling pathway, pexidartinib works to inhibit tumor cell proliferation and downmodulate cells involved in the disease, such as macrophages. It was also shown to inhibit the CD117 or proto-oncogene receptor tyrosine kinase (cKIT), mutant fms-like tyrosine kinase 3 (FLT3), and platelet-derived growth factor receptor (PDGFR)-β, which are all receptor tyrosine kinases that regulate critical cellular processes such as cell proliferation and survival.3
Target Actions Organism AMacrophage colony-stimulating factor 1 receptor inhibitorHumans AMast/stem cell growth factor receptor Kit inhibitorHumans AReceptor-type tyrosine-protein kinase FLT3 inhibitorHumans UPlatelet-derived growth factor receptor beta inhibitorHumans - Absorption
Following administration of single doses in healthy subjects and multiple doses in patients, the mean Cmax was 8625 ng/mL and the mean AUC was 77465 ngxh/mL. The median Tmax was 2.5 hours and the time to reach the steady state was approximately 7 days. Administration of pexidartinib with a high fat meal resulted in an increased drug Cmax and AUC by 100%, with a delay in Tmax by 2.5 hours.9
- Volume of distribution
The apparent volume of distribution of pexidartinib is about 187 L.9 In rats, pexidartinib was shown to penetrate into the central nervous system.10
- Protein binding
Based on the findings of in vitro plasma protein binding study, pexidartinib is about 99% bound to serum proteins, where it is extensively bound to human serum albumin by 99.9% and alpha-1-acid glycoprotein by 89.9%.9
- Metabolism
Pexidartinib primarily undergoes oxidation mediated by hepatic CYP3A4 and glucuronidation by UGT1A4. Following UGT1A4-mediated glucuronidation, a major inactive N-glucuronide metabolite is formed with approximately 10% higher exposure than the parent drug after a single dose administration of pexidartinib.9 Based on the findings of in vitro studies, CYP1A2 and CYP2C9 may also play a minor role in drug metabolism.10
- Route of elimination
Pexidartinib is predominantly excreted via feces, where fecal excretion accounts for 65% of total pexidartinib elimination. Via this route of elimination, about 44% of the compound found in feces is recovered as unchanged parent drug. The renal elimination accounts for 27% of pexidartinib elimination, where more than 10% of the compound is found as the N-glucuronide metabolite.9
- Half-life
The elimination half-life is about 26.6 hours.9
- Clearance
The apparent clearance is about 5.1 L/h.9
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
There is limited human data on the overdose of pexidartinib. In 4-week toxicology studies, the no-observed-adverse-effect levels (NOAELs) of pexidatrtinib were determined to be 10 mg/kg/day in rats and 6 mg/kg/day in dogs.10 Pexidartinib was shown to cause hepatotoxicity in clinical trials, including mixed or cholestatic hepatotoxicity,2 and embryo-fetal toxicity in animal studies.9
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir The metabolism of Abacavir can be decreased when combined with Pexidartinib. Abatacept The metabolism of Pexidartinib can be increased when combined with Abatacept. Abemaciclib The excretion of Abemaciclib can be decreased when combined with Pexidartinib. Acalabrutinib The metabolism of Pexidartinib can be decreased when combined with Acalabrutinib. Acetaminophen The metabolism of Pexidartinib can be increased when combined with Acetaminophen. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of pexidartinib.
- Avoid St. John's Wort. This herb induces the CYP3A metabolism of pexidartinib and may reduce its serum concentration.
- Do not take with or immediately after a high-fat meal. Taking pexidartinib with a high-fat meal may increase incidence and severity of adverse reactions, including hepatotoxicity.
- Take on an empty stomach. Take at least 1 hour before or 2 hours after eating a meal or snack.
- Take separate from antacids. Take antacids at least 2 hours before or after pexidartinib.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Pexidartinib hydrochloride YS6WAI3XN7 2040295-03-0 CJLUYLRKLUYCEK-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Turalio Capsule 125 mg/1 Oral Daiichi Sankyo, Inc. 2023-02-01 Not applicable US 
Turalio Capsule 200 mg/1 Oral Daiichi Sankyo Inc. 2019-08-02 2024-01-31 US
Categories
- ATC Codes
- L01EX15 — Pexidartinib
- Drug Categories
- Amines
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cancer immunotherapy
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (strength unknown)
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Hepatotoxic Agents
- Immunotherapy
- Kinase Inhibitor
- MATE 1 Inhibitors
- MATE 2 Inhibitors
- MATE inhibitors
- Narrow Therapeutic Index Drugs
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- Organic Anion Transporting Polypeptide 2B1 Inhibitors
- Protein Kinase Inhibitors
- Pyridines
- Tyrosine Kinase Inhibitors
- UGT1A1 Inhibitors
- UGT1A4 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrrolopyridines. These are compounds containing a pyrrolopyridine moiety, which consists of a pyrrole ring fused to a pyridine. Pyrrole is 5-membered ring consisting of four carbon atoms and one nitrogen atom. Pyridine is a 6-membered ring consisting of five carbon atoms and one nitrogen center.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyrrolopyridines
- Sub Class
- Not Available
- Direct Parent
- Pyrrolopyridines
- Alternative Parents
- Aminopyridines and derivatives / Substituted pyrroles / Imidolactams / Aryl chlorides / Heteroaromatic compounds / Azacyclic compounds / Organofluorides / Organochlorides / Hydrocarbon derivatives / Amines show 1 more
- Substituents
- Alkyl fluoride / Alkyl halide / Amine / Aminopyridine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Heteroaromatic compound / Hydrocarbon derivative show 10 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6783M2LV5X
- CAS number
- 1029044-16-3
- InChI Key
- JGWRKYUXBBNENE-UHFFFAOYSA-N
- InChI
- InChI=1S/C20H15ClF3N5/c21-15-6-16-14(10-28-19(16)29-11-15)5-12-2-4-18(26-7-12)27-9-13-1-3-17(25-8-13)20(22,23)24/h1-4,6-8,10-11H,5,9H2,(H,26,27)(H,28,29)
- IUPAC Name
- 5-({5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl}methyl)-N-{[6-(trifluoromethyl)pyridin-3-yl]methyl}pyridin-2-amine
- SMILES
- FC(F)(F)C1=CC=C(CNC2=NC=C(CC3=CNC4=NC=C(Cl)C=C34)C=C2)C=N1
References
- Synthesis Reference
Chen D, Zhang Y, Li J, Liu Y: Exploratory Process Development of Pexidartinib through the Tandem Tsuji–Trost Reaction and Heck Coupling. Synthesis. 2019 January 4;51(12):2564-2571. doi:10.1055/s-0037-1612421.
- General References
- Giustini N, Bernthal NM, Bukata SV, Singh AS: Tenosynovial giant cell tumor: case report of a patient effectively treated with pexidartinib (PLX3397) and review of the literature. Clin Sarcoma Res. 2018 Jul 10;8:14. doi: 10.1186/s13569-018-0101-2. eCollection 2018. [Article]
- Tap WD, Gelderblom H, Palmerini E, Desai J, Bauer S, Blay JY, Alcindor T, Ganjoo K, Martin-Broto J, Ryan CW, Thomas DM, Peterfy C, Healey JH, van de Sande M, Gelhorn HL, Shuster DE, Wang Q, Yver A, Hsu HH, Lin PS, Tong-Starksen S, Stacchiotti S, Wagner AJ: Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet. 2019 Jun 19. pii: S0140-6736(19)30764-0. doi: 10.1016/S0140-6736(19)30764-0. [Article]
- Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y. [Article]
- Espinosa I, Beck AH, Lee CH, Zhu S, Montgomery KD, Marinelli RJ, Ganjoo KN, Nielsen TO, Gilks CB, West RB, van de Rijn M: Coordinate expression of colony-stimulating factor-1 and colony-stimulating factor-1-related proteins is associated with poor prognosis in gynecological and nongynecological leiomyosarcoma. Am J Pathol. 2009 Jun;174(6):2347-56. doi: 10.2353/ajpath.2009.081037. Epub 2009 May 14. [Article]
- Hume DA, MacDonald KP: Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood. 2012 Feb 23;119(8):1810-20. doi: 10.1182/blood-2011-09-379214. Epub 2011 Dec 20. [Article]
- Nielsen SR, Schmid MC: Macrophages as Key Drivers of Cancer Progression and Metastasis. Mediators Inflamm. 2017;2017:9624760. doi: 10.1155/2017/9624760. Epub 2017 Jan 22. [Article]
- Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P: Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017 Jul;14(7):399-416. doi: 10.1038/nrclinonc.2016.217. Epub 2017 Jan 24. [Article]
- Cupp JS, Miller MA, Montgomery KD, Nielsen TO, O'Connell JX, Huntsman D, van de Rijn M, Gilks CB, West RB: Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides. Am J Surg Pathol. 2007 Jun;31(6):970-6. doi: 10.1097/PAS.0b013e31802b86f8. [Article]
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- TURALIO (PEXIDARTINIB) CAPSULES - Daiichi Sankyo, Inc. - FDA Oncologic Drugs Advisory Committee Briefing Document [Link]
- FDA approves first therapy for rare joint tumor - FDA News Release [Link]
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules (October 2022) [Link]
- External Links
- Human Metabolome Database
- HMDB0256360
- PubChem Compound
- 25151352
- PubChem Substance
- 347829117
- ChemSpider
- 35308322
- BindingDB
- 50177716
- 2183102
- ChEBI
- 145373
- ChEMBL
- CHEMBL3813873
- ZINC
- ZINC000115705166
- PDBe Ligand
- P31
- Wikipedia
- Pexidartinib
- PDB Entries
- 4r7h / 7khg
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Treatment Melanoma 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Hepatotoxicity / Tenosynovial Giant Cell Tumor 1 somestatus stop reason just information to hide 4 Completed Treatment Tenosynovial Giant Cell Tumor 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Tenosynovial Giant Cell Tumor 1 somestatus stop reason just information to hide 3 Completed Treatment Giant Cell Tumor of Tendon Sheath / Pigmented Villonodular Synovitis / Tenosynovial Giant Cell Tumor 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 125 mg/1 Capsule Oral 200 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9358235 No 2016-06-07 2033-06-08 US US8461169 No 2013-06-11 2028-04-19 US US10189833 No 2019-01-29 2036-05-05 US US9169250 No 2015-10-27 2027-11-21 US US10435404 No 2019-10-08 2038-07-24 US US8404700 No 2013-03-26 2027-11-21 US US8722702 No 2014-05-13 2027-11-21 US US7893075 No 2011-02-22 2028-10-13 US US9802932 No 2017-10-31 2036-05-05 US US10730876 No 2020-08-04 2036-05-05 US US10941142 No 2021-03-09 2038-07-24 US US10961240 No 2021-03-30 2038-07-24 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00315 mg/mL ALOGPS logP 4.64 ALOGPS logP 4.54 Chemaxon logS -5.1 ALOGPS pKa (Strongest Acidic) 15.68 Chemaxon pKa (Strongest Basic) 6.76 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 66.49 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 105.89 m3·mol-1 Chemaxon Polarizability 39.33 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0000900000-9033d1be46655d0d7b3a Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-3000900000-551e7dda2ae6dafe9b3d Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0003900000-ac37173bab41fe23aee9 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0gc0-8504900000-7fb6ebe1c5e7b18ebbb3 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03y0-0079100000-d2e6d0522405c8bbb4a3 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0gc0-9655300000-af0f16fc28e7fafbf91e Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 188.54614 predictedDeepCCS 1.0 (2019) [M+H]+ 190.90414 predictedDeepCCS 1.0 (2019) [M+Na]+ 197.53795 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of pro-inflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding, including the ERK1/2 and the JNK pathway (PubMed:20504948, PubMed:30982609). Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor. In the central nervous system, may play a role in the development of microglia macrophages (PubMed:30982608)
- Specific Function
- Atp binding
- Gene Name
- CSF1R
- Uniprot ID
- P07333
- Uniprot Name
- Macrophage colony-stimulating factor 1 receptor
- Molecular Weight
- 107982.955 Da
References
- Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- TURALIO (PEXIDARTINIB) CAPSULES - Daiichi Sankyo, Inc. - FDA Oncologic Drugs Advisory Committee Briefing Document [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1
- Specific Function
- Atp binding
- Gene Name
- KIT
- Uniprot ID
- P10721
- Uniprot Name
- Mast/stem cell growth factor receptor Kit
- Molecular Weight
- 109863.655 Da
References
- Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- TURALIO (PEXIDARTINIB) CAPSULES - Daiichi Sankyo, Inc. - FDA Oncologic Drugs Advisory Committee Briefing Document [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways
- Specific Function
- Atp binding
- Gene Name
- FLT3
- Uniprot ID
- P36888
- Uniprot Name
- Receptor-type tyrosine-protein kinase FLT3
- Molecular Weight
- 112902.51 Da
References
- Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- TURALIO (PEXIDARTINIB) CAPSULES - Daiichi Sankyo, Inc. - FDA Oncologic Drugs Advisory Committee Briefing Document [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor
- Specific Function
- Atp binding
- Gene Name
- PDGFRB
- Uniprot ID
- P09619
- Uniprot Name
- Platelet-derived growth factor receptor beta
- Molecular Weight
- 123966.895 Da
References
- Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y. [Article]
- TURALIO (PEXIDARTINIB) CAPSULES - Daiichi Sankyo, Inc. - FDA Oncologic Drugs Advisory Committee Briefing Document [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:18177842, PubMed:24641623). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:18177842). Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3 essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623). Also glucuronidates the biologically active form of vitamin D3, calcitriol, probably leading to its biliary transport and intestinal reabsorption (PubMed:18177842)
- Specific Function
- Enzyme binding
- Gene Name
- UGT1A4
- Uniprot ID
- P22310
- Uniprot Name
- UDP-glucuronosyltransferase 1A4
- Molecular Weight
- 60024.535 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- Anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558)
- Specific Function
- Enzyme binding
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1A1
- Molecular Weight
- 59590.91 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- Antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16330770, PubMed:17509534). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- Antiporter activity
- Gene Name
- SLC47A1
- Uniprot ID
- Q96FL8
- Uniprot Name
- Multidrug and toxin extrusion protein 1
- Molecular Weight
- 61921.585 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
- Specific Function
- Antiporter activity
- Gene Name
- SLC47A2
- Uniprot ID
- Q86VL8
- Uniprot Name
- Multidrug and toxin extrusion protein 2
- Molecular Weight
- 65083.915 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- Bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
- Specific Function
- Bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:14610227, PubMed:19129463, PubMed:22201122). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927)
- Specific Function
- Bile acid transmembrane transporter activity
- Gene Name
- SLCO2B1
- Uniprot ID
- O94956
- Uniprot Name
- Solute carrier organic anion transporter family member 2B1
- Molecular Weight
- 76697.93 Da
References
- FDA Approved Drug Products: Turaliotm (pexidartinib) capsules [Link]
Drug created at October 21, 2016 01:45 / Updated at August 26, 2024 19:23