Identification
- Summary
Ribociclib is a kinase inhibitor used to treat HR+, HER2- advanced or metastatic 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. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably. Ribociclib was approved by the U.S. FDA in March, 2017 as 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
Kisqali (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. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.
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 breast cancer •••••••••••• ••••••••••••••• Used in combination to treat Advanced breast cancer Regimen in combination with: Letrozole (DB01006) •••••••••••• ••••••••••••••• Used in combination to treat Metastatic breast cancer •••••••••••• ••••••••••••••• Used in combination to treat Metastatic breast cancer Regimen in combination with: Letrozole (DB01006) •••••••••••• ••••••••••••••• - 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
Not Available
- Mechanism of action
Inhibition of cyclin-dependent kinase 4 and 6 (CDK4/6) may provide protection against oncogenic processes in specific tissue types. For example, CDK4 is not required for normal mammary tissue development based on knockout mouse studies, but it is needed for growth of Ras-induced mammary tumors, suggesting a potential therapeutic window for treatment with lower toxicity. Ribociclib was reported to be a most selective CDK4/6 inhibitor and to have dose dependent antitumor activity in a number of preclinical models. It inhibited growth of tumor cells by arresting the cells at the G1 checkpoint, which prevents the tumor cells from proliferating.
Target Actions Organism ACyclin-dependent kinase 4 antagonistinhibitorHumans ACyclin-dependent kinase 6 antagonistinhibitorHumans - Absorption
Ribociclib is orally bioavailable, highly selective inhibitor of CDK4/6 kinases with inhibitory IC50 concentrations in the low nanomolar range. Following oral dosing, ribociclib was rapidly absorbed with median Tmax ranging from 1 to 5 hours. Plasma concentrations increased approximately 2- to 3-fold from Cycle 1 Day 1 to Cycle 1 Day 18/21 due to accumulation, with steady state reached by approximately Day 8 on the basis of trough concentrations after repeated daily dosing. Dose-proportionality analyses demonstrated that exposure to ribociclib increased with dose, with both Cmax and area under the curve (AUC) increasing slightly more than proportional to dose, over the dose range 50–1,200 mg/day
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
32.6 hours
- Clearance
Not Available
- 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
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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/1 Oral Novartis Pharmaceuticals Corporation 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 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 Pharmaceuticals Corporation 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 Pharmaceuticals Corporation 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 Pharmaceuticals Corporation 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]
- External Links
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Recruiting Treatment Advanced Breast Cancer / Breast Cancer / Breast Neoplasm Female / Breast Neoplasms / Female Breast Cancer / Hormone Receptor Positive Breast Carcinoma / Human Epidermal Growth Factor 2 Negative Carcinoma of Breast 1 4 Recruiting Treatment Metastatic Breast Cancer 1 4 Recruiting Treatment Solid Tumors 1 4 Terminated Basic Science Breast Cancer 1 4 Withdrawn Basic Science CYP3A4*22 1
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 - 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
- Cyclin-dependent protein serine/threonine kinase regulator activity
- Specific 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 tra...
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Cyclin-dependent protein serine/threonine kinase activity
- Specific 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 int...
- 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]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- 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]
Drug created at October 20, 2016 20:43 / Updated at January 02, 2024 23:36