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
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight; 500.5
  Topological Polar Surface Area; 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
  TTD ID: D07OZR
  INTEDE ID: DR1815

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 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

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.
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