Drug Information

Drug (ID: DG00213) and It's Reported Resistant Information

Name	Savolitinib
Synonyms	1313725-88-0; AZD-6094; AZD6094; UNII-2A2DA6857R; CHEMBL3334567; 2A2DA6857R; Savolitinib [INN]; Volitinib(Savolitinib); Savolitinib [USAN:INN]; GTPL9918; SCHEMBL12489208; EX-A845; BDBM50023342; ZINC149738712; AKOS030526403; DB12048; compound 28 [PMID: 25148209]; HY-15959; AS-35250; 1H-1,2,3-Triazolo(4,5-b)pyrazine, 1-((1S)-1-imidazo(1,2-a)pyridin-6-ylethyl)-6-(1-methyl-1H-pyrazol-4-yl)-; KB-333895; FT-0700162; J-690125; 4-{1-[(1S)-1-{imidazo[1,2-a]pyri Click to Show/Hide
Indication	In total 2 Indication(s) Renal cell carcinoma [ICD-11: 2C90] Phase 3 [1] Solid tumour/cancer [ICD-11: 2A00-2F9Z] Phase 2 [1]
Structure
Drug Resistance Disease(s)	Disease(s) with Clinically Reported Resistance for This Drug (1 diseases) Lung cancer [ICD-11: 2C25] [1]
Target	Proto-oncogene c-Met (MET)	MET_HUMAN	[1]
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Formula	C17H15N9
IsoSMILES	C[C@@H](C1=CN2C=CN=C2C=C1)N3C4=NC(=CN=C4N=N3)C5=CN(N=C5)C
InChI	1S/C17H15N9/c1-11(12-3-4-15-18-5-6-25(15)10-12)26-17-16(22-23-26)19-8-14(21-17)13-7-20-24(2)9-13/h3-11H,1-2H3/t11-/m0/s1
InChIKey	XYDNMOZJKOGZLS-NSHDSACASA-N
PubChem CID	68289010
TTD Drug ID	D0LW0T
DrugBank ID	DB12048

Type(s) of Resistant Mechanism of This Drug

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

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Lung cancer [ICD-11: 2C25]

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Hepatocyte growth factor receptor (MET)				[1]
Molecule Alteration	Missense mutation		p.D1228V	Molecule Info
Resistant Disease	Lung adenocarcinoma [ICD-11: 2C25.0]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	PC9 cells	Lung	Homo sapiens (Human)	CVCL_B260
Experiment for Molecule Alteration	Next-generation sequencing assay; Circulating-free DNA assay
Experiment for Drug Resistance	MTS assay
Mechanism Description	Our in vitro findings demonstrate that MET D1228V induces resistance to type I MET TkIs through impaired drug binding while sensitivity to type II MET TkIs is maintained.

References

Ref 1	Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer. Cancer Discov. 2016 Dec;6(12):1334-1341. doi: 10.1158/2159-8290.CD-16-0686. Epub 2016 Sep 30.