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Identification
- Summary
Ribociclib is a cyclin-dependent kinase inhibitor used to treat HR+, HER2- breast cancer.
- Brand Names
- Kisqali 200 Mg Daily Dose Carton, Kisqali Femara Co-pack
- Generic Name
- Ribociclib
- DrugBank Accession Number
- DB11730
- Background
Ribociclib is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly.
Ribociclib was approved by the FDA in March 2017 under the brand name Kisqali.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Ribociclib (DB11730)
- Weight
- Average: 434.548
Monoisotopic: 434.254257618 - Chemical Formula
- C23H30N8O
- Synonyms
- Ribociclib
- External IDs
- LEE-011
- LEE-011A
- LEE011
- LEE011A
Pharmacology
- Indication
Ribociclib is indicated in combination with an aromatase inhibitor (e.g. letrozole) for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence.6 It is also indicated, in combination with an aromatase inhibitor or fulvestrant, in adults with HR-positive, HER2-negative advanced or metastatic breast cancer.6
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 Used in combination to treat Advanced hr+/her2- breast cancer Regimen in combination with: Fulvestrant (DB00947) •••••••••••• ••••• •••••• Used in combination to treat Advanced hr+/her2- breast cancer •••••••••••• ••••• •••••• Used in combination to treat Early hr+/her2- breast cancer •••••••••••• ••••• •••• •••• •• •••••••••• •••••• Used in combination to treat Metastatic hr+/her2- breast cancer Regimen in combination with: Fulvestrant (DB00947) •••••••••••• ••••• •••••• Used in combination to treat Metastatic hr+/her2- breast cancer •••••••••••• ••••• •••••• - Contraindications & Blackbox Warnings
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Ribociclib causes concentration-dependent changes in QTcF interval.6 It should be used with caution in patients undergoing treatment with other QTc-prolonging agents, or in patients pre-disposed to the development of Torsades de Pointes (TdP) (e.g. those with long QT syndrome, LQTS).
- Mechanism of action
Ribociclib is a selective inhibitor of cyclin-dependent kinases (CDK) 4 and 6.6 These kinases are activated upon binding to D-cyclins and are downstream of signaling pathways which lead to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb). Ribociclib has been shown in vitro to decrease pRb phosphorylation, resulting in arrest in the G1 phase of the cell cycle and reduced proliferation in breast cancer-derived models.6 The inhibition of pRb phosphorylation is correlated with a decrease in the volume of tumor cells.6
Target Actions Organism ACyclin-dependent kinase 4 antagonistinhibitorHumans ACyclin-dependent kinase 6 antagonistinhibitorHumans - Absorption
The mean absolute bioavailability of ribociclib after a single oral dose of 600 mg was 65.8%.6 Following repeated 600 mg once daily administration, steady-state was generally achieved after 8 days and the mean steady-state Cmax and AUC were 1820 ng/mL and 23800 ng*h/mL, respectively.6 The Tmax of ribociclib at steady-state generally occurs between 1 and 4 hours following administration.6
- Volume of distribution
At steady-state, the apparent volume of distribution of ribociclib was 1090 L.6
- Protein binding
In vitro, ribociclib is 70% protein-bound independent of concentration.6
- Metabolism
Ribociclib undergoes extensive hepatic metabolism, primarily via oxidative reactions mediated by CYP3A4.6 Major circulating metabolites following oral administration include metabolite M13 (CCI284, N-hydroxylation), M4 (LEQ803, N-demethylation), and M1 (secondary glucuronide), each representing an estimated 9%, 9%, and 8% of total radioactivity, and 22%, 20%, and 18% of ribociclib exposure.6 Parent drug is the major circulating entity in plasma, accounting for 44% of total exposure.6
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- Route of elimination
Unchanged parent drug accounts for only 17% and 12% of the administered dose excreted in feces and urine, respectively.6 Metabolite M4 (LEQ803) represented approximately 14% and 4% of the administered dose in feces and urine, respectively.6
- Half-life
At steady-state in patients with advanced cancer, the mean plasma effective half-life of ribociclib was 32 hours.6 In healthy adults receiving the 600 mg dose, the mean apparent plasma terminal half-life of ribociclib ranged from 29.7 to 54.7 hours and mean apparent oral clearance of ribociclib ranged from 39.9 to 77.5 L/h.6
- Clearance
At steady-state in patients with advanced cancer administered receiving the 600 mg dose, the mean apparent oral clearance of ribociclib was 25.5 L/h.6 At steady-state in patients with early breast cancer administered receiving the 400 mg dose, the mean apparent oral clearance of ribociclib was 38.4 L/h.6
- Adverse Effects
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Not Available
- 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 software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be decreased when combined with Ribociclib. Abametapir The serum concentration of Ribociclib can be increased when it is combined with Abametapir. Abatacept The metabolism of Ribociclib can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Ribociclib. Abiraterone The metabolism of Abiraterone can be decreased when combined with Ribociclib. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of ribociclib.
- Avoid St. John's Wort. This herb induces CYP3A metabolism, which may reduce serum levels of ribociclib.
- Take at the same time every day. Official labeling suggests taking ribociclib in the morning.
- Take with or without food.
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 Ribociclib hydrochloride 63YF7YKW7E 1211443-80-9 JZRSIQPIKASMEV-UHFFFAOYSA-N Ribociclib succinate BG7HLX2919 1374639-75-4 NHANOMFABJQAAH-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Kisqali Tablet, film coated 200 mg Oral Novartis Europharm Limited 2020-12-16 Not applicable EU 
Kisqali Tablet, film coated 200 mg Oral Novartis Europharm Limited 2020-12-16 Not applicable EU Kisqali Tablet, film coated 200 mg/1 Oral Novartis Farma S.P.A. 2017-03-13 Not applicable US 
Kisqali Tablet, film coated 200 mg Oral Novartis Europharm Limited 2020-12-16 Not applicable EU Kisqali Tablet, film coated 200 mg Oral Novartis Europharm Limited 2020-12-16 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Kisqali Femara Co-pack Ribociclib succinate (200 mg/1) + Letrozole (2.5 mg/1) Kit; Tablet; Tablet, film coated Oral Novartis Farma S.P.A. 2017-05-04 Not applicable US Kisqali Femara Co-pack Ribociclib succinate (200 mg/1) + Letrozole (2.5 mg/1) Kit; Tablet; Tablet, film coated Oral Novartis Farma S.P.A. 2017-05-04 Not applicable US Kisqali Femara Co-pack Ribociclib succinate (200 mg/1) + Letrozole (2.5 mg/1) Kit; Tablet; Tablet, film coated Oral Novartis Farma S.P.A. 2017-05-04 Not applicable US
Categories
- ATC Codes
- L01EF02 — Ribociclib
- Drug Categories
- Amines
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cyclin-dependent kinase (CDK) inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strong)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- Highest Risk QTc-Prolonging Agents
- Kinase Inhibitor
- Narrow Therapeutic Index Drugs
- Protein Kinase Inhibitors
- Pyridines
- QTc Prolonging Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyridinylpiperazines. These are compounds containing a pyridinylpiperazine skeleton, which consists of a pyridine linked (not fused) to a piperazine by a bond by a single bond that is not part of a ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- Pyridinylpiperazines
- Alternative Parents
- N-arylpiperazines / Pyrrolo[2,3-d]pyrimidines / Pyrimidinecarboxamides / 2-heteroaryl carboxamides / Pyrrole carboxamides / Dialkylarylamines / Aminopyridines and derivatives / Aminopyrimidines and derivatives / Substituted pyrroles / Imidolactams show 8 more
- Substituents
- 2-heteroaryl carboxamide / Amine / Amino acid or derivatives / Aminopyridine / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Carboxamide group / Carboxylic acid derivative / Dialkylarylamine show 24 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- TK8ERE8P56
- CAS number
- 1211441-98-3
- InChI Key
- RHXHGRAEPCAFML-UHFFFAOYSA-N
- InChI
- InChI=1S/C23H30N8O/c1-29(2)22(32)19-13-16-14-26-23(28-21(16)31(19)17-5-3-4-6-17)27-20-8-7-18(15-25-20)30-11-9-24-10-12-30/h7-8,13-15,17,24H,3-6,9-12H2,1-2H3,(H,25,26,27,28)
- IUPAC Name
- 7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide
- SMILES
- CN(C)C(=O)C1=CC2=CN=C(NC3=CC=C(C=N3)N3CCNCC3)N=C2N1C1CCCC1
References
- General References
- Yu Q, Sicinska E, Geng Y, Ahnstrom M, Zagozdzon A, Kong Y, Gardner H, Kiyokawa H, Harris LN, Stal O, Sicinski P: Requirement for CDK4 kinase function in breast cancer. Cancer Cell. 2006 Jan;9(1):23-32. [Article]
- Rader J, Russell MR, Hart LS, Nakazawa MS, Belcastro LT, Martinez D, Li Y, Carpenter EL, Attiyeh EF, Diskin SJ, Kim S, Parasuraman S, Caponigro G, Schnepp RW, Wood AC, Pawel B, Cole KA, Maris JM: Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82. doi: 10.1158/1078-0432.CCR-13-1675. Epub 2013 Sep 17. [Article]
- Infante JR, Cassier PA, Gerecitano JF, Witteveen PO, Chugh R, Ribrag V, Chakraborty A, Matano A, Dobson JR, Crystal AS, Parasuraman S, Shapiro GI: A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) in Patients with Advanced Solid Tumors and Lymphomas. Clin Cancer Res. 2016 Dec 1;22(23):5696-5705. Epub 2016 Aug 19. [Article]
- PDF Article- Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer [Link]
- FDA approval [Link]
- FDA Approved Drug Products: Kisqali (ribociclib) tablets for oral use (September 2024) [Link]
- External Links
- Human Metabolome Database
- HMDB0257211
- KEGG Drug
- D10883
- PubChem Compound
- 44631912
- PubChem Substance
- 347828089
- ChemSpider
- 30798107
- BindingDB
- 148264
- 1873916
- ChEMBL
- CHEMBL3545110
- ZINC
- ZINC000072316335
- PharmGKB
- PA166153470
- PDBe Ligand
- 6ZZ
- Wikipedia
- Ribociclib
- PDB Entries
- 5l2t
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 Not Available Breast Cancer 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Not Available Breast Cancer / Malignant Breast Neoplasm 1 somestatus stop reason just information to hide Not Available Completed Not Available Breast Cancer 2 somestatus stop reason just information to hide Not Available Completed Not Available DILI 1 somestatus stop reason just information to hide Not Available Completed Not Available Metastatic Breast Cancer 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 200 mg Tablet Oral 254.400 mg Tablet, film coated Oral 200 mg/1 Tablet, film coated Oral 200 mg Tablet, coated Oral 200 mg Kit; tablet; tablet, film coated Oral Tablet, film coated Oral 254.4 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8685980 No 2014-04-01 2030-05-25 US US9193732 No 2015-11-24 2031-11-09 US US8415355 No 2013-04-09 2031-02-19 US US8324225 No 2012-12-04 2028-06-17 US US9416136 No 2016-08-16 2029-08-20 US US8962630 No 2015-02-24 2029-12-09 US US9868739 No 2018-01-16 2031-11-09 US US10799506 No 2020-10-13 2036-04-14 US
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.231 mg/mL ALOGPS logP 2.5 ALOGPS logP 2.38 Chemaxon logS -3.3 ALOGPS pKa (Strongest Acidic) 11.59 Chemaxon pKa (Strongest Basic) 8.87 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 91.21 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 125.59 m3·mol-1 Chemaxon Polarizability 49.13 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No 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 splash10-000i-0003900000-2808d503b498f1113305 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00ei-9008700000-5bd5740eedd313c69490 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014u-0009700000-8aa78adc3e861dd6d98d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0bu3-8049700000-4341028151396302b7d1 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-052f-4019800000-684d3cbd40213e686a8e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0fau-1559300000-67c2f9faf90f84d5f2a9 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]- 202.78386 predictedDeepCCS 1.0 (2019) [M+H]+ 205.14186 predictedDeepCCS 1.0 (2019) [M+Na]+ 211.6796 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex
- Specific Function
- ATP binding
- Gene Name
- CDK4
- Uniprot ID
- P11802
- Uniprot Name
- Cyclin-dependent kinase 4
- Molecular Weight
- 33729.55 Da
References
- Rader J, Russell MR, Hart LS, Nakazawa MS, Belcastro LT, Martinez D, Li Y, Carpenter EL, Attiyeh EF, Diskin SJ, Kim S, Parasuraman S, Caponigro G, Schnepp RW, Wood AC, Pawel B, Cole KA, Maris JM: Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82. doi: 10.1158/1078-0432.CCR-13-1675. Epub 2013 Sep 17. [Article]
- FDA Approved Drug Products: Kisqali (ribociclib) tablets for oral use (September 2024) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663)
- Specific Function
- ATP binding
- Gene Name
- CDK6
- Uniprot ID
- Q00534
- Uniprot Name
- Cyclin-dependent kinase 6
- Molecular Weight
- 36938.025 Da
References
- Rader J, Russell MR, Hart LS, Nakazawa MS, Belcastro LT, Martinez D, Li Y, Carpenter EL, Attiyeh EF, Diskin SJ, Kim S, Parasuraman S, Caponigro G, Schnepp RW, Wood AC, Pawel B, Cole KA, Maris JM: Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82. doi: 10.1158/1078-0432.CCR-13-1675. Epub 2013 Sep 17. [Article]
- FDA Approved Drug Products: Kisqali (ribociclib) tablets for oral use (September 2024) [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- Sorf A, Hofman J, Kucera R, Staud F, Ceckova M: Ribociclib shows potential for pharmacokinetic drug-drug interactions being a substrate of ABCB1 and potent inhibitor of ABCB1, ABCG2 and CYP450 isoforms in vitro. Biochem Pharmacol. 2018 Aug;154:10-17. doi: 10.1016/j.bcp.2018.04.013. Epub 2018 Apr 16. [Article]
- FDA Approved Drug Products: Kisqali (ribociclib) tablets for oral use (September 2024) [Link]
Drug created at October 20, 2016 20:43 / Updated at October 21, 2024 12:40