Details of the Drug

General Information of Drug (ID: DMYLT67)

Drug Name
TKI258
Synonyms
Dovitinib; 405169-16-6; CHIR-258; TKI-258; Chir 258; 4-Amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one; CHIR258; Dovitinib (TKI-258, CHIR-258); UNII-I35H55G906; CHEMBL522892; 804551-71-1; I35H55G906; TKI 258; 1027263-12-2; (3Z)-4-Amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydro-2H-benzimidazol-2-ylidene]-2(3H)-quinolinone; C21H21FN6O; 4-Amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one
Indication
Disease Entry ICD 11 Status REF
Renal cell carcinoma 2C90 Phase 3 [1]
Endometrial cancer 2C76 Phase 2 [2]
Triple negative breast cancer 2C60-2C65 Phase 2 [3]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski):
2		 Molecular Weight 500.5
Logarithm of the Partition Coefficient Not Available
Rotatable Bond Count 3
Hydrogen Bond Donor Count 6
Hydrogen Bond Acceptor Count 10
Chemical Identifiers
Formula
C24H29FN6O5
IUPAC Name
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one;2-hydroxypropanoic acid;hydrate
Canonical SMILES
CC(C(=O)O)O.CN1CCN(CC1)C2=CC3=C(C=C2)N=C(N3)C4=C(C5=C(C=CC=C5F)NC4=O)N.O
InChI
InChI=1S/C21H21FN6O.C3H6O3.H2O/c1-27-7-9-28(10-8-27)12-5-6-14-16(11-12)25-20(24-14)18-19(23)17-13(22)3-2-4-15(17)26-21(18)29;1-2(4)3(5)6;/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29);2,4H,1H3,(H,5,6);1H2
InChIKey
QDPVYZNVVQQULH-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
135611162
CAS Number
915769-50-5
UNII
I35H55G906
DrugBank ID
DB05928
TTD ID
D07OZR
INTEDE ID
DR1815
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Fibroblast growth factor receptor 3 (FGFR3) TTST7KB FGFR3_HUMAN Inhibitor [4]
Platelet-derived growth factor receptor (PDGFR) TTI2WET NOUNIPROTAC Inhibitor [4]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 1A2 (CYP1A2)
Main DME 		DEJGDUW CP1A2_HUMAN Substrate [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Renal cell carcinoma
ICD Disease Classification 2C90
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Fibroblast growth factor receptor 3 (FGFR3) DTT FGFR3 5.83E-03 0.08 0.1
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 7.36E-01 1.62E-02 1.08E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT01223027) Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma. U.S. National Institutes of Health.
2 Phase 2 study of dovitinib in patients with metastatic or unresectable adenoid cystic carcinoma. Cancer. 2015 Aug 1;121(15):2612-7.
3 ClinicalTrials.gov (NCT01262027) TKI258 for Metastatic Inflammatory Breast Cancer Patients. U.S. National Institutes of Health.
4 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
5 A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2018 Jan;81(1):73-80.