Identification

Name
Ribociclib
Accession Number
DB11730
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
LEE-011 / LEE-011A / LEE011 / LEE011A
Product Ingredients
IngredientUNIICASInChI Key
Ribociclib hydrochloride63YF7YKW7E1211443-80-9JZRSIQPIKASMEV-UHFFFAOYSA-N
Ribociclib succinateBG7HLX29191374639-75-4NHANOMFABJQAAH-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KisqaliTablet, film coated200 mg/1OralNovartis2017-03-13Not applicableUs
KisqaliTablet, film coated200 mg/1OralNovartis2017-03-13Not applicableUs
KisqaliTablet, film coated200 mg/1OralNovartis2017-03-13Not applicableUs
KisqaliTablet200 mgOralNovartisNot applicableNot applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Kisqali Femara Co-packRibociclib + LetrozoleKitNovartis2017-05-04Not applicableUs
Kisqali Femara Co-packRibociclib + LetrozoleKitNovartis2017-05-04Not applicableUs
Kisqali Femara Co-packRibociclib + LetrozoleKitNovartis2017-05-04Not applicableUs
Categories
UNII
TK8ERE8P56
CAS number
1211441-98-3
Weight
Average: 434.548
Monoisotopic: 434.254257618
Chemical Formula
C23H30N8O
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

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.

Structured Indications
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.

TargetActionsOrganism
ACyclin-dependent kinase 4
antagonist
inhibitor
Human
ACyclin-dependent kinase 6
antagonist
inhibitor
Human
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Ribociclib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Ribociclib.Experimental
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Ribociclib.Approved, Illicit
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Ribociclib.Approved, Illicit, Investigational
AmiodaroneThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Amiodarone.Approved, Investigational
AnagrelideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Anagrelide.Approved
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Ribociclib.Approved, Investigational, Withdrawn
ApalutamideThe serum concentration of Ribociclib can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe serum concentration of Aprepitant can be increased when it is combined with Ribociclib.Approved, Investigational
Arsenic trioxideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Arsenic trioxide.Approved, Investigational
AstemizoleThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Astemizole.Approved, Withdrawn
AtazanavirThe serum concentration of Ribociclib can be increased when it is combined with Atazanavir.Approved, Investigational
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Ribociclib.Approved
AvanafilThe serum concentration of Avanafil can be increased when it is combined with Ribociclib.Approved
AzithromycinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Azithromycin.Approved
BepridilThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Bepridil.Approved, Withdrawn
BevacizumabBevacizumab may increase the cardiotoxic activities of Ribociclib.Approved, Investigational
BoceprevirThe serum concentration of Ribociclib can be increased when it is combined with Boceprevir.Approved, Withdrawn
BudesonideThe serum concentration of Budesonide can be increased when it is combined with Ribociclib.Approved
BuspironeThe serum concentration of Buspirone can be increased when it is combined with Ribociclib.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Ribociclib.Approved
CarbamazepineThe serum concentration of Ribociclib can be decreased when it is combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Ribociclib can be increased when it is combined with Ceritinib.Approved
ChloroquineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Chloroquine.Approved, Investigational, Vet Approved
ChlorpromazineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Chlorpromazine.Approved, Investigational, Vet Approved
CilostazolThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Cilostazol.Approved, Investigational
CiprofloxacinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Ciprofloxacin.Approved, Investigational
CisaprideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Cisapride.Approved, Investigational, Withdrawn
CitalopramThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Citalopram.Approved
ClarithromycinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Clarithromycin.Approved
CobicistatThe serum concentration of Ribociclib can be increased when it is combined with Cobicistat.Approved
CocaineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Cocaine.Approved, Illicit
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Ribociclib.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Ribociclib.Approved, Investigational
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Ribociclib.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Ribociclib.Experimental
DarifenacinThe serum concentration of Darifenacin can be increased when it is combined with Ribociclib.Approved, Investigational
DarunavirThe serum concentration of Ribociclib can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Dasatinib can be increased when it is combined with Ribociclib.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Ribociclib.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Ribociclib.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Ribociclib.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Ribociclib.Approved
DisopyramideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Disopyramide.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Ribociclib.Approved, Investigational
DofetilideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Dofetilide.Approved, Investigational
DomperidoneThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Domperidone.Approved, Investigational, Vet Approved
DonepezilThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Donepezil.Approved
DronedaroneThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Dronedarone.Approved
DroperidolThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Droperidol.Approved, Vet Approved
EbastineThe serum concentration of Ebastine can be increased when it is combined with Ribociclib.Approved, Investigational
EletriptanThe serum concentration of Eletriptan can be increased when it is combined with Ribociclib.Approved, Investigational
EliglustatThe serum concentration of Eliglustat can be increased when it is combined with Ribociclib.Approved
EnzalutamideThe serum concentration of Ribociclib can be decreased when it is combined with Enzalutamide.Approved
EplerenoneThe serum concentration of Eplerenone can be increased when it is combined with Ribociclib.Approved
ErythromycinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Erythromycin.Approved, Investigational, Vet Approved
EscitalopramThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Escitalopram.Approved, Investigational
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Ribociclib.Approved
FelodipineThe serum concentration of Felodipine can be increased when it is combined with Ribociclib.Approved, Investigational
FlecainideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Flecainide.Approved, Withdrawn
FluconazoleThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Fluconazole.Approved, Investigational
FosphenytoinThe serum concentration of Ribociclib can be decreased when it is combined with Fosphenytoin.Approved, Investigational
GatifloxacinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Gatifloxacin.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Ribociclib.Experimental
GrepafloxacinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Grepafloxacin.Approved, Investigational, Withdrawn
HalofantrineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Halofantrine.Approved
HaloperidolThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Haloperidol.Approved
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Ribociclib.Approved
IbutilideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Ibutilide.Approved
IdelalisibThe serum concentration of Ribociclib can be increased when it is combined with Idelalisib.Approved
IndinavirThe serum concentration of Ribociclib can be increased when it is combined with Indinavir.Approved
ItraconazoleThe serum concentration of Ribociclib can be increased when it is combined with Itraconazole.Approved, Investigational
KetoconazoleThe serum concentration of Ribociclib can be increased when it is combined with Ketoconazole.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Ribociclib.Experimental
LevofloxacinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Levofloxacin.Approved, Investigational
Levomethadyl AcetateThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Levomethadyl Acetate.Approved, Investigational
LomitapideThe serum concentration of Lomitapide can be increased when it is combined with Ribociclib.Approved, Investigational
LopinavirThe serum concentration of Ribociclib can be increased when it is combined with Lopinavir.Approved
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Ribociclib.Approved, Investigational
LumacaftorThe serum concentration of Ribociclib can be decreased when it is combined with Lumacaftor.Approved
LurasidoneThe serum concentration of Lurasidone can be increased when it is combined with Ribociclib.Approved, Investigational
MaravirocThe serum concentration of Maraviroc can be increased when it is combined with Ribociclib.Approved, Investigational
MesoridazineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Mesoridazine.Approved, Investigational
MethadoneThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Methadone.Approved
MethotrimeprazineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Methotrimeprazine.Approved, Investigational
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Ribociclib.Experimental
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Ribociclib.Approved, Illicit
MidostaurinThe serum concentration of Ribociclib can be decreased when it is combined with Midostaurin.Approved, Investigational
MitotaneThe serum concentration of Ribociclib can be decreased when it is combined with Mitotane.Approved
MoxifloxacinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Moxifloxacin.Approved, Investigational
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Ribociclib.Approved
NefazodoneThe serum concentration of Ribociclib can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Ribociclib can be increased when it is combined with Nelfinavir.Approved
NevirapineThe serum concentration of Ribociclib can be decreased when it is combined with Nevirapine.Approved
NisoldipineThe serum concentration of Nisoldipine can be increased when it is combined with Ribociclib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Ribociclib.Experimental, Investigational
OndansetronThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Ondansetron.Approved
OuabainOuabain may decrease the cardiotoxic activities of Ribociclib.Approved
OxaliplatinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Oxaliplatin.Approved, Investigational
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Ribociclib.Approved, Vet Approved
PapaverineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Papaverine.Approved, Investigational
PentamidineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Pentamidine.Approved, Investigational
PentobarbitalThe serum concentration of Ribociclib can be decreased when it is combined with Pentobarbital.Approved, Investigational, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Ribociclib.Experimental
PhenobarbitalThe serum concentration of Ribociclib can be decreased when it is combined with Phenobarbital.Approved, Investigational
PhenytoinThe serum concentration of Ribociclib can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimozideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Pimozide.Approved
PosaconazoleThe serum concentration of Ribociclib can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe serum concentration of Ribociclib can be decreased when it is combined with Primidone.Approved, Vet Approved
ProbucolThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Probucol.Approved, Investigational
ProcainamideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Procainamide.Approved
PropofolThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Propofol.Approved, Investigational, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Ribociclib.Experimental
QuetiapineThe serum concentration of Quetiapine can be increased when it is combined with Ribociclib.Approved
QuinidineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Quinidine.Approved, Investigational
RifabutinThe serum concentration of Ribociclib can be decreased when it is combined with Rifabutin.Approved, Investigational
RifampicinThe serum concentration of Ribociclib can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Ribociclib can be decreased when it is combined with Rifapentine.Approved, Investigational
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Ribociclib.Approved
RivaroxabanThe serum concentration of Rivaroxaban can be increased when it is combined with Ribociclib.Approved
RoxithromycinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Roxithromycin.Approved, Investigational, Withdrawn
SaquinavirThe serum concentration of Ribociclib can be increased when it is combined with Saquinavir.Approved, Investigational
SevofluraneThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Sevoflurane.Approved, Vet Approved
SildenafilThe serum concentration of Sildenafil can be increased when it is combined with Ribociclib.Approved, Investigational
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Ribociclib.Approved
SirolimusThe serum concentration of Sirolimus can be increased when it is combined with Ribociclib.Approved, Investigational
SotalolThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Sotalol.Approved
SparfloxacinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Sparfloxacin.Approved, Investigational
St. John's WortThe serum concentration of Ribociclib can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Ribociclib can be increased when it is combined with Stiripentol.Approved
SulpirideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Sulpiride.Approved, Investigational
SultoprideThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Sultopride.Experimental
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Ribociclib.Approved, Investigational
TadalafilThe serum concentration of Tadalafil can be increased when it is combined with Ribociclib.Approved, Investigational
TelaprevirThe serum concentration of Ribociclib can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Ribociclib can be increased when it is combined with Telithromycin.Approved
TerfenadineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Terfenadine.Approved, Withdrawn
TerlipressinThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Terlipressin.Approved, Investigational
TerodilineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Terodiline.Experimental
ThioridazineThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Thioridazine.Approved, Withdrawn
TicagrelorThe serum concentration of Ticagrelor can be increased when it is combined with Ribociclib.Approved
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Ribociclib.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Ribociclib.Approved, Investigational
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Ribociclib.Approved, Investigational
VandetanibThe risk or severity of QTc prolongation can be increased when Ribociclib is combined with Vandetanib.Approved
VardenafilThe serum concentration of Vardenafil can be increased when it is combined with Ribociclib.Approved
VoriconazoleThe serum concentration of Ribociclib can be increased when it is combined with Voriconazole.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:16413469]
  2. 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. [PubMed:24045179]
  3. 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. [PubMed:27542767]
  4. PDF Article- Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer [Link]
  5. FDA approval [Link]
External Links
KEGG Drug
D10883
PubChem Compound
44631912
PubChem Substance
347828089
ChemSpider
30798107
BindingDB
148264
ChEMBL
CHEMBL3545110
PharmGKB
PA166153470
HET
6ZZ
Wikipedia
Ribociclib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
5l2t

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingBasic ScienceSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
0RecruitingTreatmentGlioblastoma Multiforme (GBM) / Meningiomas1
1Active Not RecruitingHealth Services ResearchAgnogenic Myeloid Metaplasia1
1Active Not RecruitingTreatmentBreast Cancer - Female / Breast Cancer - Male / Cancer, Breast1
1Active Not RecruitingTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cancer1
1Active Not RecruitingTreatmentCancer, Breast1
1Active Not RecruitingTreatmentHormone Receptor Positive, HER2-negative, Advanced Breast Cancer1
1Active Not RecruitingTreatmentLiposarcoma1
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedOtherAdvanced or Metastatic Breast Cancer1
1CompletedTreatmentAdvanced Solid Tumors1
1CompletedTreatmentAdvanced Solid Tumors / Malignant Lymphomas1
1CompletedTreatmentImpaired Hepatic Function / Normal Hepatic Function1
1CompletedTreatmentMalignant Rhabdoid Tumors (MRT), Neuroblastoma1
1RecruitingDiagnosticMetastatic Breast Cancer (MBC) / Neoplasms, Breast / Rb+ Breast Cancer1
1RecruitingTreatmentAdvanced Breast Cancer1
1RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Metastatic Malignant Solid Neoplasm1
1RecruitingTreatmentAdvanced or Metastatic ER+ Breast Cancer1
1RecruitingTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Ependymoma / Anaplastic Ganglioglioma / Anaplastic Meningioma / Anaplastic Oligodendroglioma (AO) / Atypical Teratoid/Rhabdoid Tumor / Brain Cancer / Central Nervous System Neoplasms / Choroid Plexus Carcinoma / CNS Embryonal Tumor With Rhabdoid Features / CNS Tumors / Embryonal Tumor of CNS / Embryonal Tumor With Multilayered Rosettes (ETMR) / Embryonal Tumor, NOS / Ependymoma, NOS, WHO Grade II / Ependymoma, NOS, WHO Grade III / Ependymoma, Recurrent / Ependymoma, RELA Fusion Positive / Ependymomas / Ganglioneuroblastoma of Central Nervous System / Glioblastoma, IDH-mutant / Glioblastoma, IDH-wildtype / Glioblastomas / Glioma, Diffuse Midline, H3K27M-mutant / Glioma, High Grade / Glioma, Malignant / Glioma, Recurrent High Grade / Glioma, Recurrent Malignant / Gliomas / Medulloblastoma, Chromosome 9q Loss / Medulloblastoma, G3/G4 / Medulloblastoma, Group 3 / Medulloblastoma, Group 4 / Medulloblastoma, Non-WNT Non-SHH, NOS / Medulloblastoma, Non-WNT/Non-SHH / Medulloblastoma, PTCH1 Mutation / Medulloblastoma, SHH-activated and TP53 Mutant / Medulloblastoma, SHH-activated and TP53 Wildtype / Medulloblastoma, WNT-activated / Medulloblastoma; Unspecified Site / Medulloblastomas / Medulloepithelioma / Neoplasms / Neoplasms, Brain / Neoplasms, Neuroepithelial / Neuroblastoma. CNS / Neuroepithelial Tumor / Neuroepithelial Tumor, High Grade / Papillary Tumor of the Pineal Region (High-grade Only) / Pediatric Brain Tumor / Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only) / Pinealoblastoma / Pleomorphic Xanthoastrocytoma, Anaplastic / Primitive Neuroectodermal Tumor / Recurrent Medulloblastoma / Refractory Brain Tumor1
1RecruitingTreatmentAnaplastic Astrocytoma (AA) / Bithalamic High Grade Glioma / Brain Stem Gliomas / Diffuse Intrinsic Pontine Glioma (DIPG) / Glioblastomas / High Grade Glioma (HGG) / Malignant Glioma of Brain1
1RecruitingTreatmentCancer, Breast1
1RecruitingTreatmentCancers / Neuroblastomas1
1RecruitingTreatmentCentral Nervous System Embryonal Tumor, Not Otherwise Specified / Malignant Gliomas / Recurrent Atypical Teratoid/Rhabdoid Tumor / Recurrent Childhood Ependymoma / Recurrent Diffuse Intrinsic Pontine Glioma / Recurrent Medulloblastoma / Refractory Diffuse Intrinsic Pontine Glioma1
1RecruitingTreatmentEGFR-mutant Non-small Cell Lung Cancer1
1RecruitingTreatmentGlioblastomas / Gliomas1
1RecruitingTreatmentHER2-Negative Breast Cancer / Metastatic Epithelial Ovarian Cancer / Metastatic Hormone-Receptor-Positive (HR+) Breast Cancer1
1RecruitingTreatmentImpaired Renal Function / Normal Renal Function1
1RecruitingTreatmentMetastatic Angiosarcoma / Metastatic Epithelioid Sarcoma / Metastatic Fibrosarcoma / Metastatic Leiomyosarcoma / Metastatic Liposarcoma / Metastatic Malignant Peripheral Nerve Sheath Tumor / Metastatic Synovial Sarcoma / Metastatic Undifferentiated Pleomorphic Sarcoma / Myxofibrosarcoma / Pleomorphic Rhabdomyosarcoma / Stage III Soft Tissue Sarcoma / Stage IV Soft Tissue Sarcoma / Undifferentiated (Embryonal) Sarcoma1
1RecruitingTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
1TerminatedTreatmentMalignant Lymphomas / Solid Neoplasms1
1, 2Active Not RecruitingOtherSolid Tumors Harboring a BRAF V600 Mutation1
1, 2Active Not RecruitingTreatmentBithalamic High Grade Glioma / Diffuse Intrinsic Pontine Glioma (DIPG) / High Grade Glioma (HGG)1
1, 2Active Not RecruitingTreatmentCancer, Breast1
1, 2CompletedTreatmentLocally Advanced or Metastatic NRAS Mutant Melanoma1
1, 2RecruitingTreatmentCancer, Breast2
1, 2RecruitingTreatmentChildren, Adolescents and Young Adults With Refractory or Recurrent Malignancies1
1, 2RecruitingTreatmentColorectal Cancers / Malignant Neoplasm of Pancreas / Tumors, Solid1
1, 2RecruitingTreatmentHormone-Resistant Prostate Cancer / Metastatic Hormone Refractory Prostate Cancer / Prostate Carcinoma Metastatic in the Bone / Stage IV Prostate Cancer1
1, 2RecruitingTreatmentPancreatic Adenocarcinoma Metastatic1
1, 2RecruitingTreatmentProstate Cancer1
1, 2RecruitingTreatmentTriple Negative Breast Cancer (TNBC)1
1, 2TerminatedTreatmentLocally Advanced Metastatic BRAF Mutant Melanoma / Locally Advanced or Metastatic BRAF Mutant Melanoma1
2Active Not RecruitingTreatmentGastrointestinal Cancers1
2Active Not RecruitingTreatmentLiposarcoma / Soft Tissue Sarcoma (STS)1
2Active Not RecruitingTreatmentMelanoma1
2Active Not RecruitingTreatmentTeratoma1
2Active Not RecruitingTreatmentTumors With CDK4/6 Pathway Activation1
2RecruitingTreatmentCancer, Advanced / Cancers With a Mass, Bulky Tumor, Nodule, Lump, Advanced Cancer, Advanced Solid Tumors, Advanced Solid Malignancies / Continued Access to Study Treatment(s) / Continued Access to Study Treatment(s), Cancers With a Mass, Bulky Tumor, Nodule, Lump, Advanced Cancer, Advanced Solid Tumors, Advanced Solid Malignancies / Nodules / Tumors, Solid1
2RecruitingTreatmentCancer, Breast3
2RecruitingTreatmentCarcinoma, Breast / Metastatic Breast Cancer (MBC)1
2RecruitingTreatmentEndometrial Carcinoma / Malignant Neoplasms of Female Genital Organs1
2RecruitingTreatmentEstrogen Receptor Positive / One to five years postmenopausal / RB1 Positive / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Recurrent Uterine Corpus Carcinoma1
2RecruitingTreatmentHepatocellular,Carcinoma1
2RecruitingTreatmentLiposarcoma - Well Differentiated / Liposarcoma; Mixed Type / Liposarcomas, Dedifferentiated / Soft-Tissue Sarcoma1
2RecruitingTreatmentNeuroendocrine Tumors1
2RecruitingTreatmentSoft Tissue Sarcoma (STS)1
2TerminatedNot AvailableStage I Breast Carcinoma1
3Active Not RecruitingTreatmentAdvanced, Metastatic Breast Cancer2
3Active Not RecruitingTreatmentAntineoplastic Agents / Antineoplastic Agents, Hormonal / Breast Diseases / Estrogen Receptor Antagonists / Fulvestrant / Hormone Antagonists / Hormones, Hormone Substitutes, and Hormone Antagonists / Molecular Mechanisms of Pharmacological Action / Neoplasms / Neoplasms by Site / Neoplasms, Breast / Pharmacologic Actions / Therapeutic Uses1
3Not Yet RecruitingTreatmentCancer, Breast1
3RecruitingOtherCancer, Breast1
3RecruitingTreatmentAdvanced Metastatic Breast Cancer1
3RecruitingTreatmentCancer, Breast2
3RecruitingTreatmentCancer, Breast / HER 2 Negative Breast Cancer / Hormone Receptor Positive Tumor1
3WithdrawnTreatmentCancer, Breast1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral200 mg
Tablet, film coatedOral200 mg/1
Kit
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8685980No2010-05-252030-05-25Us
US9193732No2011-11-092031-11-09Us
US8415355No2011-02-192031-02-19Us
US8324225No2008-06-172028-06-17Us
US9416136No2009-08-202029-08-20Us
US8962630No2009-12-092029-12-09Us

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.231 mg/mLALOGPS
logP2.5ALOGPS
logP2.38ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)11.59ChemAxon
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area91.21 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity125.59 m3·mol-1ChemAxon
Polarizability49.13 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Pyridinylpiperazine / N-arylpiperazine / Pyrimidinecarboxamide / Pyrrolopyrimidine / Pyrrolo[2,3-d]pyrimidine / 2-heteroaryl carboxamide / Pyrrole-2-carboxamide / Pyrrole-2-carboxylic acid or derivatives / Tertiary aliphatic/aromatic amine / Dialkylarylamine
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
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
  1. 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. [PubMed:24045179]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
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
  1. 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. [PubMed:24045179]

Drug created on October 20, 2016 14:43 / Updated on April 23, 2018 23:15