Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMYLT67)

Drug Name

TKI258 Drug Info

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

Cross-matching ID

PubChem CID: 135611162
CAS Number: CAS 915769-50-5
TTD Drug ID: DMYLT67
INTEDE Drug ID: DR1815

Molecule(s) Related to 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]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Phase 2	[5]

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The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Fibroblast growth factor receptor 3 (FGFR3)	DTT	FGFR3	6.541	6.15	4.087	6.471
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	10.036	5.779	6.508	6.481

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

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 between Disease Section and Healthy Individual Tissue

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.