參考價	￥ 1000

生化試劑

MedChemExpress (M

CAS	1620576-64-8	純度	98.63%
分子量	469.54	分子式	C??H??N?O?
供貨周期	現貨	規格	5 mg
貨號	HY-12869	應用領域	醫療衛生,化工,生物產業,制藥

AZD-8835 | MCEAZD8835 is a potent and selective inhibitor of PI3Kα and PI3Kδ with IC50s of 6.2 and 5.7 nM, respectively.

詳細介紹

MCE 的所有產品僅用作科學研究或藥證申報，我們不為任何個人用途提供產品和服務。

AZD-8835

CAS No. : 1620576-64-8

產品活性：AZD8835 is a potent and selective inhibitor of PI3Kα and PI3Kδ with IC₅₀s of 6.2 and 5.7 nM, respectively.

研究領域：PI3K/Akt/mTOR

作用靶點：PI3K

In Vitro: The selectivity profile of AZD8835 (Compound 25) among the class I PI3K isoforms is tested in enzyme and cell based assays. At the enzyme level, AZD8835 is a potent mixed inhibitor of PI3Kα (IC₅₀ 6.2 nM) and PI3Kδ (IC₅₀ 5.7 nM), with selectivity against PI3Kβ (IC₅₀ 431 nM) and PI3Kγ (IC₅₀ 90 nM). AZD8835 is also a potent inhibitor of the commonly occurring PI3Kα mutants, PI3Kα- E545K (IC₅₀ 6 nM) and PI3Kα-H1047R (IC₅₀ 5.8 nM). In cell-based assays assessing the ability to inhibit Akt phosphorylation, AZD8835 is a potent inhibitor in cells sensitive to PI3Kα inhibition (IC₅₀ 57 nM in PIK3CA mutant human breast ductal carcinoma BT474 cell line) and in cells sensitive to PI3Kδ inhibition (IC₅₀ 49 nM in Jeko-1 B cell line, but not to cells sensitive to PI3Kβ inhibition (IC₅₀ 3.5 μM in PTEN null breast adenocarcinoma MDA-MB-468 cells) or to PI3Kγ inhibition (IC₅₀ 530 nM in monocytic RAW264 cell line).

In Vivo: AZD8835 (Compound 25) displays good solubility, good permeability and low turnover in hepatocytes from various species. As expected from the in vitro data, low in vivo clearance associated with high bioavailability is seen in both rat and dog. AZD8835 shows high exposure following oral administration to SCID mice (AUC: 137 μM.h and C_max 34 μM at 50 mg/kg p.o.) and is selected for further in vivo evaluation. In a pharmacodynamic experiment following chronic oral dosing (25 mg/kg b.i.d. or 6 mg/kg b.i.d. of AZD8835) in nude mice bearing mutant H1047R PI3Kα SKOV-3 tumour xenografts, target modulation is assessed by measuring Akt phosphorylation levels at Ser473 at 30 minutes and 8 hours. At both doses, strong inhibition of Akt phosphorylation is observed at the 30 minute timepoint. At 8 hours, significant inhibition is still seen at the 25 mg/kg dose, whereas no inhibition is seen at the lower dose of 6 mg/kg, consistent with the lower plasma concentrations observed.

品牌介紹:
•   MCE (MedChemExpress) 擁有200 多種*僅有化合物庫，我們致力于為*科研客戶提供前沿的高品質小分子活性化合物；
•   50,000 多種高選擇性抑制劑、激動劑涉及各熱門信號通路及疾病領；
•   產品種類涵蓋各種重組蛋白，多肽，常用試劑盒，更有 PROTAC、ADC 等特色產品，廣泛應用于新藥研發、生命科學等科研項目；
•   提供虛擬篩選，離子通道篩選，代謝組學分析檢測分析，藥物篩選等專業技術服務；
•   設有專業的實驗中心和嚴格的質控、驗證體系；
•   提供 LC/MS、NMR、HPLC、手性分析、元素分析等各項質檢報告，確保產品的高純度、高品質；
•   產品的生物活性多經各國客戶實驗驗證；
•   Nature, Cell, Science 等多種頂級期刊及制藥 Patent 收錄了MCE客戶的科研成果；
•   專業團隊跟蹤最新的制藥及生命科學研究進展，為您提供*新的活性化合物；
•   與世界各大制藥公司及著名科研機構建立了長期的合作。