ribociclib indications/contra

Stem definitionDrug idCAS RN
cyclin dependant kinase inhibitors 5218 1211441-98-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ribociclib
  • ribociclib succinate
  • LEE011
  • LEE 011
  • kisqali
  • LEE011-BBA
  • LEE011A
Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to D-cyclins and play a crucial role in signaling pathways which lead to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb). In vitro, ribociclib decreased pRb phosphorylation leading to arrest in the G1 phase of the cell cycle and reduced cell proliferation in breast cancer cell lines. In vivo, treatment with single agent ribociclib in a rat xenograft model with human tumor cells led to decreased tumor volumes, which correlated with inhibition of pRb phosphorylation. In studies using patient-derived estrogen receptor positive breast cancer xenograft models, combination of ribociclib and antiestrogen (e.g. letrozole) resulted in increased tumor growth inhibition compared to each drug alone.
  • Molecular weight: 434.55
  • Formula: C23H30N8O
  • CLOGP: 1.80
  • LIPINSKI: 0
  • HAC: 9
  • HDO: 2
  • TPSA: 91.21
  • ALOGS: -3.28
  • ROTB: 5

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
Aug. 22, 2017 EMA Novartis Europharm Ltd
March 13, 2017 FDA NOVARTIS PHARMS CORP

FDA Adverse Event Reporting System

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MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neutropenia 76.02 36.62 25 292 33361 3352181
Nausea 63.25 36.62 32 285 129613 3255929

Pharmacologic Action:

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SourceCodeDescription
ATC L01XE42 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000175082 Kinase Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Hormone receptor positive malignant neoplasm of breast indication 417181009

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.03 Basic
pKa2 6.09 Basic
pKa3 5.48 Basic
pKa4 0.57 Basic

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 200MG BASE KISQALI NOVARTIS PHARMS CORP N209092 March 13, 2017 RX TABLET ORAL 9416136 Aug. 20, 2029 IN COMBINATION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER-2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
N/A,EQ 200MG BASE KISQALI FEMARA CO-PACK (COPACKAGED) NOVARTIS PHARMS CORP N209935 May 4, 2017 RX TABLET, TABLET ORAL 9416136 Aug. 20, 2029 IN COMBINATION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER-2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
EQ 200MG BASE KISQALI NOVARTIS PHARMS CORP N209092 March 13, 2017 RX TABLET ORAL 8962630 Dec. 9, 2029 IN COMBINATION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER-2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
N/A,EQ 200MG BASE KISQALI FEMARA CO-PACK (COPACKAGED) NOVARTIS PHARMS CORP N209935 May 4, 2017 RX TABLET, TABLET ORAL 8962630 Dec. 9, 2029 IN COMBINATION WITH AN AROMATASE INHIBITOR AS INITIAL ENDOCRINE-BASED THERAPY FOR TREATMENT OF POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER-2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 200MG BASE KISQALI NOVARTIS PHARMS CORP N209092 March 13, 2017 RX TABLET ORAL March 13, 2022 NEW CHEMICAL ENTITY
N/A,EQ 200MG BASE KISQALI FEMARA CO-PACK (COPACKAGED) NOVARTIS PHARMS CORP N209935 May 4, 2017 RX TABLET, TABLET ORAL March 13, 2022 NEW CHEMICAL ENTITY

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Cyclin-dependent kinase 4 Kinase INHIBITOR IC50 8 SCIENTIFIC LITERATURE DRUG LABEL
Cyclin-dependent kinase 6 Kinase INHIBITOR IC50 7.41 SCIENTIFIC LITERATURE DRUG LABEL

External reference:

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IDSource
1873916 RXNORM
017131 NDDF
4036504 VANDF
N0000193345 NDFRT
d08533 MMSL
732257004 SNOMEDCT_US
BG7HLX2919 UNII
1374639-75-4 SECONDARY_CAS_RN
CHEMBL3545110 ChEMBL_ID
7383 IUPHAR_LIGAND_ID
44631912 PUBCHEM_CID
9968 INN_ID
C000589651 MESH_SUPPLEMENTAL_RECORD_UI
CHEMBL3707266 ChEMBL_ID
DB11730 DRUGBANK_ID
6ZZ PDB_CHEM_ID
D10883 KEGG_DRUG

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
KISQALI HUMAN PRESCRIPTION DRUG LABEL 1 0078-0860 TABLET, FILM COATED 200 mg ORAL NDA 17 sections
KISQALI HUMAN PRESCRIPTION DRUG LABEL 1 0078-0867 TABLET, FILM COATED 200 mg ORAL NDA 17 sections
KISQALI HUMAN PRESCRIPTION DRUG LABEL 1 0078-0874 TABLET, FILM COATED 200 mg ORAL NDA 17 sections
KISQALI FEMARA CO-PACK HUMAN PRESCRIPTION DRUG LABEL 2 0078-0909 KIT 200 mg None NDA 17 sections
KISQALI FEMARA CO-PACK HUMAN PRESCRIPTION DRUG LABEL 2 0078-0916 KIT 200 mg None NDA 17 sections
KISQALI FEMARA CO-PACK HUMAN PRESCRIPTION DRUG LABEL 2 0078-0923 KIT 200 mg None NDA 17 sections