Tirbanibulin

Identification

Summary

Tirbanibulin is a tyrosine kinase and tubulin inhibitor used to treat actinic keratosis on the face or scalp.

Brand Names
Klisyri
Generic Name
Tirbanibulin
DrugBank Accession Number
DB06137
Background

Tirbanibulin (KX-O1 or KX2–391) is a dual inhibitor of Src Kinase and tubulin.4 On December 14, 2020, tirbanibulin was approved by the FDA for the topical treatment of actinic keratosis on the face or scalp. It is marketed under the brand name Klisyri.12 Actinic keratosis is a chronic condition characterized by lesions, which can potentially transform into invasive squamous cell carcinoma with a risk of 1% over 10 years.3,7 Tirbanibulin blocks the molecular pathways that promote the proliferation, survival, and metastasis of malignant cells. Tirbanibulin exhibits antitumour effects in vitro and in vivo 9 and has been investigated for its antitumor efficacy in the management of various cancers, such as prostate cancer and breast cancer.4,5,6

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 431.536
Monoisotopic: 431.220891806
Chemical Formula
C26H29N3O3
Synonyms
  • Tirbanibulin
External IDs
  • KX-01
  • KX-2-391
  • KX-2391
  • KX2-391

Pharmacology

Indication

Tirbanibulin is indicated for the topical treatment of actinic keratosis on the face or scalp.11

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
Pharmacodynamics

In clinical trials composed comprising patients with actinic keratosis of the face or scalp, tirbanibulin promoted complete clearance of actinic keratosis lesions at day 57 in treated areas in 44-54% of patients compared to 5-13% of patients who received the placebo.11 Actinic keratosis is a chronic, pre-malignant condition characterized by lesions and proliferation of neoplastic keratinocytes.3 Tirbanibulin mediates an anti-proliferative effect by inhibiting tubulin polymerization and Src kinase signalling.1

Tirbanibulin inhibited primary tumour growth and metastasis in many preclinical animal models of cancer.2,4,5,6 In human triple-negative breast cancer, or estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2)-negative tumour, xenografts, tirbanibulin suppressed tumour growth and metastasis.4 Tirbanibulin was also shown to restore functional ERα expression in ERα-negative breast tumours.10 Tirbanibulin promoted synergistic tumour growth inhibition of breast cancer cell lines when used in combination with tamoxifen 5,10 and paclitaxel.4

In a clinical trial comprising patients with advanced solid tumours, dose-limiting toxicities of tirbanibulin included elevated liver transaminases, neutropenia and fatigue.6

Mechanism of action

Src tyrosine kinases regulate normal cell growth: the expression of Src kinase is upregulated during the normal hair cycle during the proliferative anagen phase. Additionally, Src tyrosine kinases act as key modulators of cancer cell proliferation, survival, angiogenesis, migration, invasion and metastasis. Src is frequently upregulated in various epithelial tumours including colon, breast and pancreas compared with the adjacent normal tissues. The expression and activity of Src are also enhanced in human actinic keratosis, which is characterized by hyperproliferative premalignant skin lesions.8 The pathogenesis of actinic keratosis commonly involves skin inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of keratinocyte growth and proliferation, and tissue remodelling.7 In vitro studies suggest that Src plays a predominant role in the early stages of human skin tumour development, rather than at later stages of tumour progression.8

The exact mechanism of tirbanibulin as a topical treatment of actinic keratosis has not been fully elucidated;11 however, it mainly works by inhibiting fast proliferating cells.3 Tirbanibulin is a non-ATP competitive Src kinase inhibitor and tubulin polymerization inhibitor. It binds to the peptide substrate binding site of Src, a primary target of tirbanibulin, and blocking its downstream signalling pathways that promote cancer cell migration, proliferation, and survival.3,5 Tublin is responsible for cell migration, protein transport, and mitosis: tibranibulin directly binds to the colchicine-binding site of beta-tubulin and causes induces tubulin depolymerization.2 It is also hypothesized that inhibition of Src can also contribute to the inhibitory effects on microtubule polymerization.9 At low nanomolar concentrations, tirbanibulin induces G2/M phase cell cycle arrest in a reversible 2,5 and dose-dependent manner. By inhibiting microtubule polymerization, tirbanibulin also induces mitotic catastrophe.9

TargetActionsOrganism
AProto-oncogene tyrosine-protein kinase Src
inhibitor
Humans
ATubulin beta chain
inhibitor
Humans
Absorption

Tirbanibulin demonstrates good oral bioavailability.2 Following topical administration of doses ranging from 54 to 295 mg on the face or scalp, the steady-state concentration of tirbanibulin was achieved by 72 hours. At five days following initial administration, the mean Cmax was 0.34±0.30 ng/mL in subjects who received topical treatment on the face and 0.18±0.10 ng/mL in subjects who received topical treatment on the scalp. The mean AUC24 was 5.0±3.9 h x ng/mL in subjects who received topical treatment on the face and 3.2±1.9 h x ng/mL in subjects who received topical treatment on the scalp. The median Tmax was about seven hours.11

Volume of distribution

There is limited information on the volume of distribution of tirbanibulin. In mouse HT29 xenograft studies, the tissue to plasma ration of tirbanibulin was 1.52.6

Protein binding

Tirbanibulin is 88% bound to plasma proteins and the extent of plasma protein binding is independent of drug concentrations in the range of 0.01 to 10 µg/mL.11

Metabolism

In vitro, tirbanibulin is mainly metabolized by CYP3A4, and to a lesser extent, CYP2C8. In adult subjects with actinic keratosis, detected metabolites were KX2-5036 and KX2-5163, which were pharmacologically inactive metabolites with the highest plasma concentrations of 0.09 ng/mL and 0.12 ng/mL, respectively.11

Route of elimination

There is limited information on the route of elimination of tirbanibulin.

Half-life

The half-life is about 4 hours.6

Clearance

There is limited information on the clearance rate of tirbanibulin.

Adverse Effects
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
Toxicity

The LD50 value of tirbanibulin has not been determined. While there is limited information on overdose from tirbanibulin, it may lead to an increase in the incidence and severity of local skin reactions.11

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.
Not Available
Food Interactions
No interactions found.

Products

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
KlisyriOintment10 mg/1gTopicalAlmirall, LLC2020-12-14Not applicableUS flag

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
4V9848RS5G
CAS number
897016-82-9
InChI Key
HUNGUWOZPQBXGX-UHFFFAOYSA-N
InChI
InChI=1S/C26H29N3O3/c30-26(28-19-21-4-2-1-3-5-21)18-24-9-6-23(20-27-24)22-7-10-25(11-8-22)32-17-14-29-12-15-31-16-13-29/h1-11,20H,12-19H2,(H,28,30)
IUPAC Name
N-benzyl-2-(5-{4-[2-(morpholin-4-yl)ethoxy]phenyl}pyridin-2-yl)acetamide
SMILES
O=C(CC1=CC=C(C=N1)C1=CC=C(OCCN2CCOCC2)C=C1)NCC1=CC=CC=C1

References

General References
  1. Kempers S, DuBois J, Forman S, Poon A, Cutler E, Wang H, Cutler D, Fang J, Kwan R: Tirbanibulin Ointment 1% as a Novel Treatment for Actinic Keratosis: Phase 1 and 2 Results. J Drugs Dermatol. 2020 Nov 1;19(11):1093-1100. doi: 10.36849/JDD.2020.5576. [Article]
  2. Niu L, Yang J, Yan W, Yu Y, Zheng Y, Ye H, Chen Q, Chen L: Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of beta-tubulin explains KXO1's low clinical toxicity. J Biol Chem. 2019 Nov 29;294(48):18099-18108. doi: 10.1074/jbc.RA119.010732. Epub 2019 Oct 18. [Article]
  3. Cramer P, Stockfleth E: Actinic keratosis: where do we stand and where is the future going to take us? Expert Opin Emerg Drugs. 2020 Mar;25(1):49-58. doi: 10.1080/14728214.2020.1730810. Epub 2020 Feb 20. [Article]
  4. Anbalagan M, Ali A, Jones RK, Marsden CG, Sheng M, Carrier L, Bu Y, Hangauer D, Rowan BG: Peptidomimetic Src/pretubulin inhibitor KX-01 alone and in combination with paclitaxel suppresses growth, metastasis in human ER/PR/HER2-negative tumor xenografts. Mol Cancer Ther. 2012 Sep;11(9):1936-47. doi: 10.1158/1535-7163.MCT-12-0146. Epub 2012 Jul 10. [Article]
  5. Anbalagan M, Carrier L, Glodowski S, Hangauer D, Shan B, Rowan BG: KX-01, a novel Src kinase inhibitor directed toward the peptide substrate site, synergizes with tamoxifen in estrogen receptor alpha positive breast cancer. Breast Cancer Res Treat. 2012 Apr;132(2):391-409. doi: 10.1007/s10549-011-1513-3. Epub 2011 Apr 21. [Article]
  6. Antonarakis ES, Heath EI, Posadas EM, Yu EY, Harrison MR, Bruce JY, Cho SY, Wilding GE, Fetterly GJ, Hangauer DG, Kwan MF, Dyster LM, Carducci MA: A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2013 Apr;71(4):883-92. doi: 10.1007/s00280-013-2079-z. Epub 2013 Jan 13. [Article]
  7. Dodds A, Chia A, Shumack S: Actinic keratosis: rationale and management. Dermatol Ther (Heidelb). 2014 Jun;4(1):11-31. doi: 10.1007/s13555-014-0049-y. Epub 2014 Mar 14. [Article]
  8. Serrels B, Serrels A, Mason SM, Baldeschi C, Ashton GH, Canel M, Mackintosh LJ, Doyle B, Green TP, Frame MC, Sansom OJ, Brunton VG: A novel Src kinase inhibitor reduces tumour formation in a skin carcinogenesis model. Carcinogenesis. 2009 Feb;30(2):249-57. doi: 10.1093/carcin/bgn278. Epub 2008 Dec 5. [Article]
  9. Kim S, Min A, Lee KH, Yang Y, Kim TY, Lim JM, Park SJ, Nam HJ, Kim JE, Song SH, Han SW, Oh DY, Kim JH, Kim TY, Hangauer D, Lau JY, Im K, Lee DS, Bang YJ, Im SA: Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis. Cancer Res Treat. 2017 Jul;49(3):643-655. doi: 10.4143/crt.2016.168. Epub 2016 Oct 6. [Article]
  10. Anbalagan M, Sheng M, Fleischer B, Zhang Y, Gao Y, Hoang V, Matossian M, Burks HE, Burow ME, Collins-Burow BM, Hangauer D, Rowan BG: Dual Src Kinase/Pretubulin Inhibitor KX-01, Sensitizes ERalpha-negative Breast Cancers to Tamoxifen through ERalpha Reexpression. Mol Cancer Res. 2017 Nov;15(11):1491-1502. doi: 10.1158/1541-7786.MCR-16-0297-T. Epub 2017 Jul 27. [Article]
  11. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
  12. Drugs.com: Klisyri FDA Approval History [Link]
  13. Cayman Chemical: KX2-391 Safety Data Sheet [Link]
ChemSpider
24633341
BindingDB
50303801
RxNav
2471078
ChEMBL
CHEMBL571546
ZINC
ZINC000043152787
PDBe Ligand
DN0
Wikipedia
Tirbanibulin
PDB Entries
6knz

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentActinic Keratosis (AK)2
2CompletedTreatmentActinic Keratosis (AK)1
2CompletedTreatmentBone-Metastatic, Castration-Resistant Prostate Cancer1
1CompletedTreatmentActinic Keratosis (AK)2
1CompletedTreatmentAcute Myeloid Leukemia (AML)1
1CompletedTreatmentDisorders, Lymphoproliferative / Malignant Lymphomas / Small Intestine Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentMalignant Lymphomas / Tumors, Solid1
1, 2Unknown StatusTreatmentBreast Cancer / Malignant Neoplasm of Stomach / Unspecified Adult Solid Tumor, Protocol Specific1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
OintmentTopical10 mg/1g
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7851470No2009-02-022029-02-02US flag
US10617693No2018-03-122038-03-12US flag
US8980890No2005-12-282025-12-28US flag
US7300931No2006-02-062026-02-06US flag
US10323001No2007-12-282027-12-28US flag
US8236799No2005-12-282025-12-28US flag
US10669236No2018-09-072038-09-07US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0248 mg/mLALOGPS
logP3.26ALOGPS
logP3.21ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)15.36ChemAxon
pKa (Strongest Basic)6.63ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.69 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity124.86 m3·mol-1ChemAxon
Polarizability48.49 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets
Accelerate your drug discovery research
with our fully connected ADMET & drug target dataset.
Learn more
Accelerate your drug discovery research with our ADMET & drug target dataset
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Tirbanibulin binds to the substrate-binding site of Src kinase. Antonarakis et al. (2013) showed that the IC50 for Src inhibition in human tumour cells is about 25 nM in the absence of human plasma and about 100 nM in the presence of human plasma. An approximate 4-fold reduction in potency for Src inhibition is attributed to extensive plasma protein binding of tirbanibulin (88%).
General Function
Sh3/sh2 adaptor activity
Specific Function
Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion recept...
Gene Name
SRC
Uniprot ID
P12931
Uniprot Name
Proto-oncogene tyrosine-protein kinase Src
Molecular Weight
59834.295 Da
References
  1. Anbalagan M, Carrier L, Glodowski S, Hangauer D, Shan B, Rowan BG: KX-01, a novel Src kinase inhibitor directed toward the peptide substrate site, synergizes with tamoxifen in estrogen receptor alpha positive breast cancer. Breast Cancer Res Treat. 2012 Apr;132(2):391-409. doi: 10.1007/s10549-011-1513-3. Epub 2011 Apr 21. [Article]
  2. Antonarakis ES, Heath EI, Posadas EM, Yu EY, Harrison MR, Bruce JY, Cho SY, Wilding GE, Fetterly GJ, Hangauer DG, Kwan MF, Dyster LM, Carducci MA: A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2013 Apr;71(4):883-92. doi: 10.1007/s00280-013-2079-z. Epub 2013 Jan 13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Tirbanibulin binds to the colchicine-binding site of β-tubulin. Antonarakis et al. (2013) showed that IC50 for tubulin polymerization inhibition in human tumour cells is about 125 nM in the absence of plasma and about 500 nM in the presence of plasma. An approximate 4-fold reduction in potency for tubulin polymerization inhibition is attributed to extensive plasma protein binding of tirbanibulin (88%).
General Function
Ubiquitin protein ligase binding
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBB
Uniprot ID
P07437
Uniprot Name
Tubulin beta chain
Molecular Weight
49670.515 Da
References
  1. Niu L, Yang J, Yan W, Yu Y, Zheng Y, Ye H, Chen Q, Chen L: Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of beta-tubulin explains KXO1's low clinical toxicity. J Biol Chem. 2019 Nov 29;294(48):18099-18108. doi: 10.1074/jbc.RA119.010732. Epub 2019 Oct 18. [Article]
  2. Anbalagan M, Ali A, Jones RK, Marsden CG, Sheng M, Carrier L, Bu Y, Hangauer D, Rowan BG: Peptidomimetic Src/pretubulin inhibitor KX-01 alone and in combination with paclitaxel suppresses growth, metastasis in human ER/PR/HER2-negative tumor xenografts. Mol Cancer Ther. 2012 Sep;11(9):1936-47. doi: 10.1158/1535-7163.MCT-12-0146. Epub 2012 Jul 10. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP3A4 with an IC50 value of >17 µM.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP2C8 with an IC50 value of >17 µM.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP1A2 with an IC50 value of >17 µM.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP2B6 with an IC50 value of >17 µM.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP2C9 with an IC50 value of >17 µM.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP2C19 with an IC50 value of >17 µM.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP2D6 with an IC50 value of >17 µM.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]

Drug created on November 18, 2007 18:30 / Updated on February 21, 2021 18:51