A939572 _SCD1 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEA939572Cat. No.: HY-50709CAS No.: 1032229-33-6分式: CHClNO分量: 387.86作靶點(diǎn): Stearoyl-CoA Desaturase (SCD)作通路: Metabolic Enzyme/Protease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 : 56 mg/mL (1

2、44.38 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.5782 mL 12.8912 mL 25.7825 mL5 mM 0.5156 mL 2.5782 mL 5.1565 mL10 mM 0.2578 mL 1.2891 mL 2.5782 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。BIOLOGICAL ACTIVITY物活性 A939572種服有效的硬脂酰 CoA 去飽和酶 1 SCD1 抑

3、制劑，作于 mSCD1 和 hSCD1，IC50 分別為 4nM 和 37 nM。IC50 & Target IC50: 1體外研究A939572 exhibits robust in vivo activity with dose-dependent desaturation index lowering effects 1.A9395721/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEis a small molecule that specifically inhibits SCD1 enzymatic activity. A939572

4、 demonstrates a significantdose-dependent decrease in proliferation in Caki1, A498, Caki2, and ACHN at day 5 (IC50s of 65 nM, 50 nM,65 nM, and 6 nM, respectively). In A939572 (SCDi) treated Caki1 and A498 cells, all five ER stress relatedgenes are expressed at significantly increased levels compared

5、 to DMSO+BSA control, and this elevatedexpression can be blocked with the addition of OA-BSA 2.體內(nèi)研究 Athymic nude (nu/nu) mice bearing A498 ccRCC xenografts are treated with A939572 (30mg/kg, p.o.) andTem individually or in combination over the course of four weeks, and tumor volume (mm3) is recorded

6、.A939572 and Tem monotherapy generate similar growth responses with approximately 20-30% reductions intumor volume (vs. placebo control) being observed upon study completion, with values reaching statisticalsignificance only within the last week of treatment. The combination group yields over a 60%

7、decrease intumor volume (vs. placebo control) by study completion with significant reductions recorded afterapproximately 1 week of treatment 2.PROTOCOLCell Assay 2 Cells are plated (0.5 or 1105/well) in 24-well plates in triplicate. Cells are counted using a Coulter ParticleCounter. Oleic acid-albu

8、min is added to media at 5Mol. A939572 stocks are prepared in DMSO.Temsirolimus dosing is performed. Soft agar cultures are prepared by diluting 2 growth medium 1:1 in 1.5%SeaplaqueGTG agarose, with 500 cells/plate in 60mm culture dishes. Colonies are stained with Giemsaand counted after 3wks 2.MCE

9、has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 A498 cells are subcutaneously implanted in athymic nu/nu mice at 1106 cells/mouse in 50% Matrigel.Tumors reach 50 mm3 prior to 4 wk treatment. A939572 is re-suspended in strawberr

10、y flavored Kool-Aidin sterilized H2O (0.2 g/mL) vehicle at 30 mg/kg in a 50 L dose. Mice are orally fed by using a syringe toadminister the 50 L dose twice daily/mouse. This modified method is found to be effective and less stressfulon the mice. Temsirolimus is solubilized in 30% ethanol/saline and

11、administered via intraperitoneal injectionat 10 mg/kg in a 50 L dose once every 72 hrs/mouse. Tumor volumes are calculated using the formula0.5236 (L*W*H) and body weight are measured every 3 days.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶(hù)使本產(chǎn)品發(fā)表的

12、科研獻(xiàn) Oncogene. 2016 Jan 28;35(4):427-37. PLoS Pathog. 2018 Aug 17;14(8):e1007261. Stem Cells. 2018 Oct;36(10):1603-1616. J Cell Mol Med. 2019 Mar;23(3):2064-2076. Front Pharmacol. 2018 Jan 4;8:960.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您邊的抑制劑師www.MedChe

13、mEREFERENCES1. Xin Z, et al. Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors. Bioorg Med Chem Lett. 2008 Aug1;18(15):4298-302.2. von Roemeling CA, et al. Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma. ClinCancer Res. 2013 May 1;19(9):2368-80.McePdf