Successful, we will reply to you quickly.OK
Please select the quantity.OK
Your message is being sent, please wait.Close
Send mail failed, please send again!Close
Products are for research use only. Not for human use. We do not sell to patients.
(GDC0623; GDC 0623)
GDC-0623 Chemical Structure
|Product name: GDC-0623|
|Cat. No.: HY-15610|
GDC-0623 is a potent, ATP-uncompetitive inhibitors of MEK1(Ki=0.13 nM, +ATP); 6-fold weaker potency against HCT116 (KRAS(G13D), EC50=42 nM) versus A375 (BRAF(V600E), EC50=7 nM).
IC50 value: 0.13 nM (Ki, +ATP); 7 nM (EC50, A375 BRAF(V600E) ) 
|M.Wt||456.21||Storage||Please store the product under the recommended conditions in the Certificate of Analysis.|
|Solvent & Solubility||
DMSO: ≥ 30 mg/mL
|1 mg||5 mg||10 mg|
|1 mM||2.1920 mL||10.9599 mL||21.9197 mL|
|5 mM||0.4384 mL||2.1920 mL||4.3839 mL|
|10 mM||0.2192 mL||1.0960 mL||2.1920 mL|
. Hatzivassiliou G, et al. Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers. Nature. 2013 Sep 12;501(7466):232-6.
KRAS and BRAF activating mutations drive tumorigenesis through constitutive activation of the MAPK pathway. As these tumours represent an area of high unmet medical need, multiple allosteric MEK inhibitors, which inhibit MAPK signalling in both genotypes, are being tested in clinical trials. Impressive single-agent activity in BRAF-mutant melanoma has been observed; however, efficacy has been far less robust in KRAS-mutant disease. Here we show that, owing to distinct mechanisms regulating MEK activation in KRAS- versus BRAF-driven tumours, different mechanisms of inhibition are required for optimal antitumour activity in each genotype. Structural and functional analysis illustrates that MEK inhibitors with superior efficacy in KRAS-driven tumours (GDC-0623 and G-573, the former currently in phase I clinical trials) form a strong hydrogen-bond interaction with S212 in MEK that is critical for blocking MEK feedback phosphorylation by wild-type RAF. Conversely, potent inhibition of active, phosphorylated MEK is required for strong inhibition of the MAPK pathway in BRAF-mutant tumours, resulting in superior efficacy in this genotype with GDC-0973 (also known as cobimetinib), a MEK inhibitor currently in phase III clinical trials. Our study highlights that differences in the activation state of MEK in KRAS-mutant tumours versus BRAF-mutant tumours can be exploited through the design of inhibitors that uniquely target these distinct activation states of MEK. These inhibitors are currently being evaluated in clinical trials to determine whether improvements in therapeutic index within KRAS versus BRAF preclinical models translate to improved clinical responses in patients.
AS703026(Pimasertib) is a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2 with IC50 of 5 nM-2 (mu)M in MM cell lines.
AZD8330(ARRY-424704; ARRY-704) is a novel, selective, non-ATP competitive MEK 1/2 inhibitor with IC50 of 7 nM.
BIX02188 is a selective inhibitor of MEK5 with IC50 of 4.3 nM, also inhibits ERK5 catalytic activity with IC50 of 810 nM, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2.
BIX02189 is a selective MEK5/ERK5 inhibitor with an IC50 of 59 nM.
Isorhamnetin is an O-methylated flavonol, a flavonoid aglucon.
MEK inhibitor is a potent MEK inhibitor, antitumor agent.
MEK162(ARRY-438162; ARRY-162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM.
OTS964 is a potent TOPK inhibitor with an IC50 value of 28 nM.