GDC-0623

Catalog No.S7553 Batch:S755301

Technical Data

Formula	C₁₆H₁₄FIN₄O₃
Molecular Weight	456.21	CAS No.	1168091-68-6
Solubility (25°C)*	In vitro	DMSO	91 mg/mL (199.46 mM)
		Ethanol	5 mg/mL (10.95 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

GDC-0623 (G-868) is a potent and ATP-uncompetitive MEK1 inhibitor with K_i of 0.13 nM. Phase 1.

Targets

MEK1 ^[1]

0.13 nM

In vitro

In a panel of mutant cancer cell lines, GDC-0623 inhibits cellular proliferation with EC50 of 4 nM, 53 nM, 11 nM, 18 nM and 94 nM for A375 (BRAFV600E), HCT116 (KRASG13D), COLO 205 (V600E), HT-29 (V600E), and HCT116 (G13D) cells, respectively. ^[1] In isogenic KRAS HCT116 and mutant KRAS SW620 colon cells, GDC-0623 upregulates BIM via its loss of phosphorylation at Ser69. GDC-0623 plus ABT-263 induces a synergistic cell apoptosis. ^[2]

In vivo

In vivo, GDC-0623 (40 mg/kg, p.o.) causes potent tumor growth inhibition (TGI) in mouse MiaPaCa-2 (120%), A375 (102%) and HCT116 (115%) xenografts. ^[1]

Protocol (from reference)

Kinase Assay:^{^[1]}	In vitro Kinase assays 0.14 μM of purified inactive recombinant MEK-1 (Upstate) protein is preincubated with inhibitors in 15 μL of kinase buffer including (20 mM MOPS pH7.2, 25 mM beta glycerol phosphate, 5 mM EGTA, 1 mM sodium orthovanadate, 1 mM DTT, 100 μM ATP, 15 mM MgCl₂). After incubating 10 minutes at 30°C, 1 ng of BRAF, CRAF or BRAF V600E combined with 0.5 μg of inactive recombinant ERK2 is added to the reaction in total volume of 20 μL. After incubating 30 minutes at 30°C the reaction is stopped by adding Laemmle sample buffer. Enzyme activity is measured by determining level of phosphor-MEK by SDS-PAGE. Immunoreactive proteins are visualized with SuperSignal West Pico Chemiluminescent Substrate.
Animal Study:^{^[1]}	Animal Models Mice bearing MiaPaCa-2, A375 and HCT116 xenografts Dosages 40 mg/kg daily Administration p.o.

Kinase Assay:^{^[1]}

In vitro Kinase assays
0.14 μM of purified inactive recombinant MEK-1 (Upstate) protein is preincubated with inhibitors in 15 μL of kinase buffer including (20 mM MOPS pH7.2, 25 mM beta glycerol phosphate, 5 mM EGTA, 1 mM sodium orthovanadate, 1 mM DTT, 100 μM ATP, 15 mM MgCl₂). After incubating 10 minutes at 30°C, 1 ng of BRAF, CRAF or BRAF V600E combined with 0.5 μg of inactive recombinant ERK2 is added to the reaction in total volume of 20 μL. After incubating 30 minutes at 30°C the reaction is stopped by adding Laemmle sample buffer. Enzyme activity is measured by determining level of phosphor-MEK by SDS-PAGE. Immunoreactive proteins are visualized with SuperSignal West Pico Chemiluminescent Substrate.

Animal Study:^{^[1]}

Animal Models
Mice bearing MiaPaCa-2, A375 and HCT116 xenografts
Dosages
40 mg/kg daily
Administration
p.o.

References

Customer Product Validation

: Data from [Data independently produced by , , Mol Cell Proteomics, 2017, 16(2):265-277]

Selleck's GDC-0623 has been cited by 14 publications

High In Vitro and In Vivo Activity of BI-847325, a Dual MEK/Aurora Kinase Inhibitor, in Human Solid and Hematologic Cancer Models [ Cancer Res Commun, 2023, 3(10):2170-2181]	PubMed: 37830744
Neuronal differentiation drives the antitumor activity of mitogen-activated protein kinase kinase (MEK) inhibition in glioblastoma [ Neurooncol Adv, 2023, 5(1):vdad132]	PubMed: 38130900
High In Vitro and In Vivo Activity of BI-847325, a Dual MEK/Aurora Kinase Inhibitor, in Human Solid and Hematologic Cancer Models [ Cancer Res Commun, 2023, 3(10):2170-2181]	PubMed: 37830744
DAMPs Released From Injured Renal Tubular Epithelial Cells Activate Innate Immune Signals in Healthy Renal Tubular Epithelial Cells [ Transplantation, 2022, 106-8:1589-1599]	PubMed: 34954736
Efficacy of Targeted Radionuclide Therapy Using [131I]ICF01012 in 3D Pigmented BRAF- and NRAS-Mutant Melanoma Models and In Vivo NRAS-Mutant Melanoma [ Cancers (Basel), 2021, 13(6)1421]	PubMed: 33804655
Sensitivity and Resistance of Oncogenic RAS-Driven Tumors to Dual MEK and ERK Inhibition [ Cancers (Basel), 2021, 13(8)1852]	PubMed: 33924486
MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways [ Int J Endocrinol, 2021, 2021:5720145]	PubMed: 34976051
CAGE-prox: A Unified Approach for Time-Resolved Protein Activation in Living Systems [ Curr Protoc, 2021, 1(6):e180]	PubMed: 34165886
Time-resolved protein activation by proximal decaging in living systems [Wang J, et al. Nature, 2019, 569(7757):509-513]	PubMed: 31068699
Genetic Heterogeneity of BRAF Fusion Kinases in Melanoma Affects Drug Responses. [ Cell Rep, 2019, 29(3):573-588]	PubMed: 31618628

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