Ravoxertinib-GDC-0994-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERavoxertinibCat. No.: HY-15947CAS No.: 1453848-26-4Synonyms: GDC-0994分式: CHClFNO分量: 440.86作靶點(diǎn): ERK作通路: MAPK/ERK Pathway; Stem Cell/Wnt儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 35 mg/m

2、L (79.39 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.2683 mL 11.3415 mL 22.6829 mL5 mM 0.4537 mL 2.2683 mL 4.5366 mL10 mM 0.2268 mL 1.1341 mL 2.2683 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) GDC-0994 is prepared in vehicle (0.5% CMCNa+0.1%

3、 Tween80+ddH2O)3.BIOLOGICAL ACTIVITY物活性 Ravoxertinib (GDC-0994)可服的 ERK 激酶抑制劑，抑制 ERK1 和 ERK2 的IC50 分別為6.1 nM 和 3.1 nM。IC50 & Target ERK2 ERK1 p-RSK1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE3.1 nM (IC50) 6.1 nM (IC50) 12 nM (IC50)體外研究 Ravoxertinib (GDC-0994) also inhibits p90RSK with an IC50 of

4、 12 nM 1. Ravoxertinib (GDC-0994) is highlyselective for ERK1 and ERK2, with biochemical potency of 1.1 nM and 0.3 nM, respectively 2.體內(nèi)研究 In CD-1 mice, a 10 mg/kg oral dose of Ravoxertinib (GDC-0994) is sufficient to achieve the desired targetcoverage for at least 8 h 1. Daily, oral dosing of Ravox

5、ertinib results in significant single-agent activity inmultiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice2.PROTOCOLAnimal Mice 1Administration 1 PK/PD data for Ravoxertinib (GDC-0994) in the HCT116 mouse xenograft model. HCT116 tumors areestablished

6、in nude mice to a tumor volume of 400-600 mm3. Mice are treated with a single oral dose of 22at 15, 30, or 100 mg/kg versus vehicle control alone (40% PEG400/60% (10% HPCD) follow by tumor andplasma collection at 2, 8, 16, and 24 h postdose. Tumor levels of phosphorylated p90RSK (pRSK) relativetotal

7、 p90RSK (tRSK) are measured by quantitative Western blot and are normalized to vehicle control at 2 hpostdose (set to 100%). Plasma and tumor concentrations are measured by LCMS.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cell. 2018 Sep

8、20;175(1):186-199.e19. Am J Physiol Heart Circ Physiol. 2018 Mar 1;314(3):H580-H592. Methods Mol Biol. 2018;1711:351-398. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Blake JF, et al. Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydro

9、xyethyl)-4-(2-(1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Developme2. Kirk Robarge, et al. Abstract DDT02-03: Discovery of GDC-0994, a potent and selective ERK1/2 inhibitor in early clinical development.Proceedings: AACR Annual Meeting 2014; April 5-9, 2014.3. Huang X, et al. Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2-Aberrant Solid Tumors. Cell. 2018 Sep20;175(1):186-199.e19.McePdfHeightCaution: Product has not been fully validate