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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2D Structure
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Physico-chemical Properties
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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
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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)
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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].
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