Successful, we will reply to you quickly.

OK

Please select the quantity.

OK

Your message is being sent, please wait.

Close

test

Close

Send mail failed, please send again!

Close

Products are for research use only. Not for human use. We do not sell to patients.

Signaling Pathway

GDC-0623

HY-15610

(GDC0623; GDC 0623)

GDC-0623

GDC-0623 Chemical Structure

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).

Size Price Stock Quantity
Free sample   Apply now  
10 mM * 1 mL in DMSO $165 In-stock
5 mg $150 In-stock
10 mg $250 In-stock
50 mg $650 In-stock
100 mg $980 In-stock
200 mg Get quote
500 mg Get quote
Size Price Stock Quantity
Free sample   Apply now  
10 mM * 1 mL in DMSO €162 In-stock
5 mg €147 In-stock
10 mg €245 In-stock
50 mg €637 In-stock
100 mg €960 In-stock
200 mg Get quote
500 mg Get quote

* Please select Quantity before adding items.

Bulk Inquiry

Inquiry Information
Product name: GDC-0623
Cat. No.: HY-15610

GDC-0623 Data Sheet

  • View current batch:

    Purity: 98.17%

  • Pdf Version Network Version

    DataSheet

    Pdf Version Network Version

    MSDS

    Pdf Version

    COA

    Pdf Version

    NMR

    Pdf Version

    LCMS

Related Compound Libraries

Biological Activity of GDC-0623

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) ) [1]
Target: MEK1

Chemical Information

M.Wt 456.21 Storage Please store the product under the recommended conditions in the Certificate of Analysis.
Formula C16H14FIN4O3
CAS No 1168091-68-6
Solvent & Solubility

DMSO:40mg/mL

Preparing Stock Solutions

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

References on GDC-0623

[1]. 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.
Abstract
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.

Inhibitor Kit

Related MEK Products

  • AS703026

    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

    AZD8330(ARRY-424704; ARRY-704) is a novel, selective, non-ATP competitive MEK 1/2 inhibitor with IC50 of 7 nM.

  • BIX02188

    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

    BIX02189 is a selective MEK5/ERK5 inhibitor with an IC50 of 59 nM.

  • CI-1040

  • MEK inhibitor

    MEK inhibitor is a potent MEK inhibitor, antitumor agent.

  • MEK162

    MEK162(ARRY-438162; ARRY-162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM.

  • OTS-964

    OTS964 is a potent TOPK inhibitor with an IC50 value of 28 nM.

  • PD0325901

  • PD318088

    PD318088 is a non-ATP competitive allosteric MEK1/2 inhibitor, binds simultaneously with ATP in a region of the MEK1 active site that is adjacent to the ATP-binding site.

MORE