Description
DCC-2618 is a small-molecule inhibitor ofKIT kinases with IC50 values of 6 nM, 9 nM, 18 nM, 5 nM, 14 nM and 9 nM for wt c-KIT, KIT V654A, KIT T670I, KIT D816H, KIT D816V and KIT JMD ΔVV/D816V respectively.
Product Overview
IC50: 6 nM, 9 nM, 18 nM, 5 nM, 14 nM and 9 nM for wt c-KIT, KIT V654A, KIT T670I, KIT D816H, KIT D816V and KIT JMD ΔVV/D816V, respectively. DCC-2618 is a small-molecule inhibitor of KIT kinases. Gastrointestinal stromal tumors (GIST) are driven by gain-of-function mutations of the KIT (approx 90%) or PDGFR (approx 10%) receptor tyrosine kinases. DCC-2618 has been designed to effectively inhibit the imatinib and sunitinib-sensitive KIT juxtamenbrane domin mutants as well as secondary resistant KIT iniase-domain mutants. Clinical trial: A Phase I trial with refractory GIST patients is planned.
Synonyms
DCC2618; DCC 2618
IC50
6 nM; 9 nM; 18 nM; 5 nM; 14 nM; 9 nM
Molecular Formula
C26H21F2N5O3
Chemical Name
1-N-[2,5-difluoro-4-[2-(1-methylpyrazol-4-yl)pyridin-4-yl]oxyphenyl]-1-N-phenylcyclopropane-1,1-dicarboxamide
Solubility
Soluble in DMSO
Shipping Conditions
Evaluation sample solution: ship with blue ice. All other available size: ship with RT, or blue ice upon request
In vitro
DCC-2618 is a kinase switch inhibitor that can control drug resistant mutants of KIT and PDGFR in GIST. DCC-2618 acts by imposing an inactive conformation (shape) of highly resistant and aggressive secondary mutations of KIT kinase.
In vivo
DCC-2618 inhibits KIT in GIST tumor xenografts after single dose. At the doses of 50 and 25 mpk, DCC-2618 showed promising potency on pKIT (Y703) with the inhibition ranging from 39% to 79% 2-12 hrs after the administration.
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