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Ribociclib

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Also known as Lee-011LEE-011ALEE011LEE011ANVP-LEE011US8962630, 74RibocicilibRIBOCICLIB (LEE011)RibociclibKisqali

Summary

Ribociclib (CHEMBL3545110) is an approved small molecule targeting CDK4; indicated across 36 conditions including breast carcinoma and breast neoplasm; with CIViC clinical evidence for 10 variant-indication associations (e.g. CCND1 Amplification in cancer).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • Targets: 1 (CDK4)
  • Indications: 36 conditions
  • Clinical trials: 165
  • Precision-oncology evidence (CIViC): 10 variant–indication associations
  • Chemistry: 434.5 Da · C23H30N8O

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL3545110
NameRibociclib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID44631912
Molecular formulaC23H30N8O
Molecular weight434.5
InChIKeyRHXHGRAEPCAFML-UHFFFAOYSA-N

SMILES: CN(C)C(=O)C1=CC2=CN=C(N=C2N1C3CCCC3)NC4=NC=C(C=C4)N5CCNCC5

IUPAC name: 7-cyclopentyl-N,N-dimethyl-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide

Also known as: Lee-011, LEE-011, LEE-011A, LEE011, LEE011A, NVP-LEE011, Ribociclib, RIBOCICLIB, US8962630, 74, Ribocicilib, RIBOCICLIB (LEE011), Ribociclib; Kisqali

Parent form; salt/anhydrous children: CHEMBL3707266, CHEMBL4468983

Patent coverage: 3,338 distinct patent families (8,018 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 7,689 (96%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
CDK4cyclin dependent kinase 4Inhibition858%P11802

Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: Cyclin-dependent kinase 4/cyclin D1, CDK9/cyclin T1, CDK6/cyclin D3, CDK6/cyclin D1, Cyclin-dependent kinase 6, Calcium/calmodulin-dependent protein kinase type II subunit delta, Cyclin-dependent kinase 2, CDK2/Cyclin A2, CDK4/Cyclin D3, Cyclin-dependent kinase 9.

Bioactivity

ChEMBL activities: 51 potent at pChembl ≥ 5 of 56 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
CDK48.7IC502nMCHEMBL_ACT_18784863
CDK48.67IC502.14nMCHEMBL_ACT_27913460
CDK68.22IC506nMCHEMBL_ACT_18784867
CDK48IC5010nMCHEMBL_ACT_15678965
CDK48IC5010nMCHEMBL_ACT_17669115
CDK48IC5010nMCHEMBL_ACT_19027213
CDK48IC5010nMCHEMBL_ACT_19027230
CDK48IC5010nMCHEMBL_ACT_24862060
CDK48IC5010nMCHEMBL_ACT_24954270
CDK48IC5010nMCHEMBL_ACT_24984405
CDK48IC5010nMCHEMBL_ACT_26023244
CDK48IC5010nMCHEMBL_ACT_26214034
CDK48IC5010nMCHEMBL_ACT_29144566
CDK48IC5010nMCHEMBL_ACT_29252813
CDK67.91IC5012.23nMCHEMBL_ACT_29310543
CDK47.89IC5013nMCHEMBL_ACT_18112224
CDK47.89IC5013nMCHEMBL_ACT_18260674
CDK47.89IC5013nMCHEMBL_ACT_19144125
CCND17.71IC5019.5nMCHEMBL_ACT_22443526
CDK47.65IC5022.5nMCHEMBL_ACT_22443557
CDK47.63IC5023.62nMCHEMBL_ACT_29310545
CDK67.57IC5026.9nMCHEMBL_ACT_27913463
CCND37.55IC5028nMCHEMBL_ACT_18693873
CDK47.54IC5029nMCHEMBL_ACT_22912954
CDK47.52IC5030nMCHEMBL_ACT_18870878
CDK47.52IC5030nMCHEMBL_ACT_22930719
CDK67.41IC5039nMCHEMBL_ACT_15678966
CDK67.41IC5039nMCHEMBL_ACT_19027219
CDK67.41IC5039nMCHEMBL_ACT_24862062
CDK67.41IC5039nMCHEMBL_ACT_24954271

Target pathways

Aggregated over 1 target gene(s): CDK4.

Top Reactome pathways

50 total, by targets touching each:

PathwayTargetsGenes
Developmental Biology1CDK4
Reproduction1CDK4
Meiosis1CDK4
Signal Transduction1CDK4
Cell Cycle1CDK4
Disease1CDK4
SCF(Skp2)-mediated degradation of p27/p211CDK4
Generic Transcription Pathway1CDK4
Cellular responses to stress1CDK4
Oxidative Stress Induced Senescence1CDK4
Senescence-Associated Secretory Phenotype (SASP)1CDK4
Cellular Senescence1CDK4
Oncogene Induced Senescence1CDK4
RMTs methylate histone arginines1CDK4
Chromatin modifying enzymes1CDK4
Transcriptional regulation of white adipocyte differentiation1CDK4
Mitotic G1 phase and G1/S transition1CDK4
Chromatin organization1CDK4
Cyclin E associated events during G1/S transition1CDK4
G1/S Transition1CDK4
Cyclin D associated events in G11CDK4
G1 Phase1CDK4
S Phase1CDK4
Cell Cycle, Mitotic1CDK4
Cyclin A:Cdk2-associated events at S phase entry1CDK4
RNA Polymerase II Transcription1CDK4
Gene expression (Transcription)1CDK4
Ubiquitin-dependent degradation of Cyclin D1CDK4
Signaling by PTK61CDK4
PTK6 Regulates Cell Cycle1CDK4

Dominant GO biological processes

GO termTargets
G1/S transition of mitotic cell cycle1
signal transduction1
positive regulation of cell population proliferation1
response to xenobiotic stimulus1
regulation of G2/M transition of mitotic cell cycle1
regulation of gene expression1
positive regulation of G2/M transition of mitotic cell cycle1
positive regulation of fibroblast proliferation1
cell division1
regulation of cell cycle1
regulation of transcription initiation by RNA polymerase II1
regulation of type B pancreatic cell proliferation1
cellular response to lipopolysaccharide1
cellular response to interleukin-41
cellular response to phorbol 13-acetate 12-myristate1

Indications & clinical

Indications

36 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
breast carcinoma3MONDO:0004989EFO:0000305
breast neoplasm3MONDO:0021100EFO:0003869
melanoma2MONDO:0005105EFO:0000756
liposarcoma2MONDO:0005060EFO:0000569
neoplasm2MONDO:0005070EFO:0000616
hepatocellular carcinoma2MONDO:0007256EFO:0000182
ovarian carcinoma2MONDO:0005140EFO:0001075
dedifferentiated liposarcoma2MONDO:0020563EFO:0003085
tumor of uterus2MONDO:0021353EFO:0003859
fallopian tube carcinoma2MONDO:0006206EFO:1000251
soft tissue sarcoma2MONDO:0018078EFO:1001968
carcinoma2MONDO:0004993EFO:0000313
thymus neoplasm2MONDO:0005197EFO:0002626
lung neuroendocrine neoplasm2MONDO:0005454EFO:0005220
neuroendocrine neoplasm2MONDO:0019496EFO:1001901
fallopian tube neoplasm2MONDO:0021092MONDO:0002158
teratoma2MONDO:0002601MONDO:0002601
ovarian cancer2MONDO:0008170MONDO:0008170
lymphoma1MONDO:0005062EFO:0000574
glioblastoma1MONDO:0018177EFO:0000519
head and neck squamous cell carcinoma1MONDO:0010150EFO:0000181
metastatic prostate carcinoma1MONDO:0004956EFO:0000196
neuroblastoma1MONDO:0005072EFO:0000621
anaplastic astrocytoma1MONDO:0016684EFO:0002499
non-small cell lung carcinoma1MONDO:0005233EFO:0003060
rhabdoid tumor1MONDO:0002728EFO:0005701
acute lymphoblastic leukemia1MONDO:0004967EFO:0000220
kidney disorder1MONDO:0005240EFO:0003086
diffuse intrinsic pontine glioma1MONDO:0006033EFO:1000026
primary myelofibrosis1MONDO:0009692MONDO:0044903
paraganglioma1MONDO:0000448EFO:1000453
colorectal neoplasm1MONDO:0005335MONDO:0005575
glioma1MONDO:0021042MONDO:0100342

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 165.

Phase distribution

PhaseTrials
PHASE147
PHASE244
PHASE324
PHASE1/PHASE224
Not specified18
PHASE45
EARLY_PHASE13

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05161195PHASE4ACTIVE_NOT_RECRUITINGRoll-over Study to Allow Continued Access to Ribociclib
NCT05203172PHASE4RECRUITINGThe FLOTILLA Study: Providing Continued Access to The Study Medicines Encorafenib and Binimetinib for Participants in Prior Clinical Trials
NCT05452213PHASE4RECRUITINGComprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
NCT04657679PHASE4TERMINATEDPharmacokinetics and Pharmacogenomics of Ribociclib in Race-based Cohorts
NCT07487129PHASE4COMPLETEDClinical and Pharmacoeconomic Assessment of CDK4/6 Inhibitors for Treatment of Breast Cancer in Egypt
NCT02344472PHASE3ACTIVE_NOT_RECRUITINGDetect V / CHEVENDO (Chemo vs. Endo)
NCT03701334PHASE3ACTIVE_NOT_RECRUITINGA Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer
NCT04862663PHASE3RECRUITINGCapivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
NCT04964934PHASE3ACTIVE_NOT_RECRUITINGPhase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)
NCT05207709PHASE3ACTIVE_NOT_RECRUITINGRibociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype
NCT05827081PHASE3RECRUITINGPhase IIIb Study of Ribociclib + ET in Early Breast Cancer
NCT06065748PHASE3RECRUITINGA Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer)
NCT06377852PHASE3RECRUITINGThe CDK4/6 Inhibitor Dosing Knowledge (CDK) Study
NCT06380751PHASE3RECRUITINGSaruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer
NCT06760637PHASE3ACTIVE_NOT_RECRUITINGStudy of PF-07220060 With Letrozole in Adults With HR-positive HER2-negative Breast Cancer Who Have Not Received Anticancer Treatment for Advanced/Metastatic Disease
NCT07085767PHASE3RECRUITINGPalazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer
NCT07174336PHASE3RECRUITINGA Study of Tersolisib (LY4064809/STX-478) With Other Anti-Cancer Treatments in Participants With Advanced Breast Cancer With a Genetic Change (PIK3CA)
NCT07340658PHASE3NOT_YET_RECRUITINGA Study to Investigate the Efficacy and Safety of Letrozole SIE Compared With Femara® (Both Combined With the CDK4/6 Inhibitor Ribociclib) in Postmenopausal Women With HR-Positive, HER2-Negative, Inoperable Locally Advanced or Metastatic Breast Cancer
NCT07492641PHASE3RECRUITINGBGB-43395 Plus Letrozole Versus CDK4/6i Plus Letrozole for Patients With Advanced or Metastatic HR+/HER2- Breast Cancer Who Have Not Received Prior Treatment for Advanced or Metastatic Disease
NCT01958021PHASE3COMPLETEDStudy of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer
NCT02278120PHASE3COMPLETEDStudy of Efficacy and Safety in Premenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer
NCT02422615PHASE3COMPLETEDStudy of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer.
NCT02941926PHASE3COMPLETEDStudy to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With HR+ HER2- aBC
NCT03050398PHASE3TERMINATEDA Companion Sample Collection Protocol to Support the Discovery of Breast Cancer Aberrations With Treatment of CDK4/6 Therapy/LEE011/Ribociclib
NCT03081234PHASE3WITHDRAWNAdjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- Intermediate Risk Early Breast Cancer
NCT03096847PHASE3COMPLETEDStudy for Women and Men With Hormone-receptor Positive Locally Advanced or Metastatic Breast Cancer
NCT03439046PHASE3COMPLETEDStudy of the Molecular Features of Postmenopausal Women With HR+ HER2-negative aBC on First-line Treatment With Ribociclib and Letrozole and, in Patients With a PIK3CA Mutation, on Second-line Treatment With Alpelisib Plus Fulvestrant
NCT03462251PHASE3COMPLETEDRibociclib and Endocrine Therapy or Chemotherapy With or Without Bevacizumab for Metastatic Breast Cancer in First Line
NCT03905343PHASE3TERMINATEDRibociclib-endocrine Combination Therapy Versus Chemotherapy as 1st Line in Visceral mBC
NCT01872260PHASE1/PHASE2ACTIVE_NOT_RECRUITINGStudy of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer
NCT02712723PHASE2ACTIVE_NOT_RECRUITINGLetrozole Plus Ribociclib or Placebo as Neo-adjuvant Therapy in ER-positive, HER2-negative Early Breast Cancer
NCT02813135PHASE1/PHASE2RECRUITINGEuropean Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors
NCT02925234PHASE2RECRUITINGThe Drug Rediscovery Protocol (DRUP Trial)
NCT02934568PHASE2ACTIVE_NOT_RECRUITINGRibociclib (LEE011) Rollover Study for Continued Access
NCT03008408PHASE2ACTIVE_NOT_RECRUITINGA Phase II, Two-Arm Study of Everolimus and Letrozole, +/- Ribociclib (Lee011) in Patients With Advanced or Recurrent Endometrial Carcinoma
NCT03090165PHASE1/PHASE2ACTIVE_NOT_RECRUITINGRibociclib and Bicalutamide in AR+ TNBC
NCT03114527PHASE2ACTIVE_NOT_RECRUITINGPhase II Trial of Ribociclib and Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS)
NCT03285412PHASE2ACTIVE_NOT_RECRUITINGCDK 4/6 Inhibitor, Ribociclib, With Adjuvant Endocrine Therapy for ER-positive Breast Cancer
NCT03673124PHASE2ACTIVE_NOT_RECRUITINGRibociclib and Letrozole Treatment in Ovarian Cancer
NCT03944434PHASE2ACTIVE_NOT_RECRUITINGFACILE: FeAsibility of First-line RiboCIclib in OLdEr Patients with Advanced Breast Cancer

Clinical evidence (CIViC)

Variant × indication × effect (10 predictive associations from 10 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
CCND1 AmplificationCancerSensitivity/ResponseRibociclibCIViC BEID7789
NRAS MutationSkin MelanomaSensitivity/ResponseRibociclib + BinimetinibCIViC BEID2931
FGFR1 Amplification AND ZNF703 AmplificationBreast CancerResistanceRibociclib + LetrozoleCIViC BEID12531
RB1 MutationBreast CancerResistancePalbociclib + RibociclibCIViC CEID6097
CCND1 OverexpressionAnaplastic Thyroid CarcinomaSensitivity/ResponseRibociclibCIViC DEID7790
CDK4 EXPRESSIONChildhood B-cell Acute Lymphoblastic LeukemiaSensitivity/ResponseRibociclib + DexamethasoneCIViC DEID7798
CDK6 EXPRESSIONChildhood B-cell Acute Lymphoblastic LeukemiaSensitivity/ResponseDexamethasone + RibociclibCIViC DEID7801
PIK3CA MutationBreast CancerSensitivity/ResponseRibociclib + Phosphatidylinositide 3-Kinase InhibitorCIViC DEID1600
SMARCA4 LossOvarian Small Cell CarcinomaSensitivity/ResponsePalbociclib + Ribociclib + AbemaciclibCIViC DEID7154
CDK4 OverexpressionAlveolar RhabdomyosarcomaResistanceRibociclib + PalbociclibCIViC DEID7138

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 3 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

57 molecules share ≥1 primary target. Top 57 by shared-target count:

MoleculeSourceStatusShared targets
ABEMACICLIBChEMBLPhase 4 (approved)CDK4
CERITINIBChEMBLPhase 4 (approved)CDK4
DABRAFENIBChEMBLPhase 4 (approved)CDK4
ENCORAFENIBChEMBLPhase 4 (approved)CDK4
FEDRATINIBChEMBLPhase 4 (approved)CDK4
GILTERITINIBChEMBLPhase 4 (approved)CDK4
NINTEDANIBChEMBLPhase 4 (approved)CDK4
PALBOCICLIBChEMBLPhase 4 (approved)CDK4
SUNITINIBChEMBLPhase 4 (approved)CDK4
TRILACICLIBChEMBLPhase 4 (approved)CDK4
ALVOCIDIBChEMBLPhase 3CDK4
DALPICICLIBChEMBLPhase 3CDK4
DINACICLIBChEMBLPhase 3CDK4
DOVITINIBChEMBLPhase 3CDK4
LEROCICLIBChEMBLPhase 3CDK4
LESTAURTINIBChEMBLPhase 3CDK4
QUERCETINChEMBLPhase 3CDK4
RUBOXISTAURINChEMBLPhase 3CDK4
AT-7519ChEMBLPhase 2CDK4
AT-9283ChEMBLPhase 2CDK4
ATIRMOCICLIBChEMBLPhase 2CDK4
BI-2536ChEMBLPhase 2CDK4
CROZBACICLIBChEMBLPhase 2CDK4
CT-7001ChEMBLPhase 2CDK4
CULMERCICLIBChEMBLPhase 2CDK4
CYC-065ChEMBLPhase 2CDK4
EBVACICLIBChEMBLPhase 2CDK4
ECIRUCICLIBChEMBLPhase 2CDK4
ELLAGIC ACIDChEMBLPhase 2CDK4
INDIRUBINChEMBLPhase 2CDK4
INIXACICLIBChEMBLPhase 2CDK4
ISTISOCICLIBChEMBLPhase 2CDK4
LY-2090314ChEMBLPhase 2CDK4
MILCICLIBChEMBLPhase 2CDK4
NARAZACICLIBChEMBLPhase 2CDK4
REBASTINIBChEMBLPhase 2CDK4
RG-547ChEMBLPhase 2CDK4
RIVICICLIBChEMBLPhase 2CDK4
RONICICLIBChEMBLPhase 2CDK4
SELICICLIBChEMBLPhase 2CDK4
SU-014813ChEMBLPhase 2CDK4
TEGTOCICLIBChEMBLPhase 2CDK4
ULECACICLIBChEMBLPhase 2CDK4
VORUCICLIBChEMBLPhase 2CDK4
ZEMIRCICLIBChEMBLPhase 2CDK4
AfatinibPubChemApprovedCDK4
BinimetinibPubChemApprovedCDK4
CrizotinibPubChemApprovedCDK4
dacomitinibPubChemApprovedCDK4
FostamatinibPubChemApprovedCDK4
GefitinibPubChemApprovedCDK4
IdelalisibPubChemApprovedCDK4
PazopanibPubChemApprovedCDK4
PomalidomidePubChemApprovedCDK4
regorafenibPubChemApprovedCDK4
SelumetinibPubChemApprovedCDK4
TrametinibPubChemApprovedCDK4

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot