ribociclib   Click here for help

GtoPdb Ligand ID: 7383

Synonyms: example 74 [US8962630] [3] | Kisqali® | LEE-011 | LEE011
Approved drug PDB Ligand
ribociclib is an approved drug (FDA & EMA (2017))
Compound class: Synthetic organic
Comment: Ribociclib is a selective, orally available inhibitor of the cyclin-dependent kinases CDK4 and CDK6 [1,3].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

ribociclib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 91.21
Molecular weight 434.25
XLogP 2.88
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CN(C(=O)c1cc2c(n1C1CCCC1)nc(nc2)Nc1ccc(cn1)N1CCNCC1)C
Isomeric SMILES CN(C(=O)c1cc2c(n1C1CCCC1)nc(nc2)Nc1ccc(cn1)N1CCNCC1)C
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)
InChI Key RHXHGRAEPCAFML-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Ribociclib is FDA approved as initial therapy for treatment of postmenopausal women with HR+ve, HER2-ve advanced or metastatic breast cancer, in combination with the aromatase inhibitor letrozole. It was approved under the FDA Breakthrough Therapy designation and Priority Review programs. Phase 3 trial NCT01958021 results are reported in [6]. Early phase trials in other cancers are underway. To view the current list of ribociclib trials link to ClinicalTrials.gov.
In July 2018, the FDA expanded ribociclib's approval to include the treatment of pre/perimenopausal women with HR+ve, HER2-ve advanced/metastatic breast cancer, in combination with an aromatase inhibitor. This expanded approval was based on results from clinical trial NCT02278120 [10].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The cyclin D-CDK4/6 (CDK-4/6:INK4:Rb) pathway is key to regulating cell growth in many types of human cancer [2,7,9], such as genetic subtypes of non-small cell lung cancer (NSCLC, [4,7,11], melanoma, Mantle cell lymphoma (MCL), and ovarian and breast cancers [4-5]. Inhibiting this pathway prevents cell cycle transition from G1 to S phase, induces cell senescence and in some cases results in apoptosis [4].
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)