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Afuresertib HCl

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Chemical Structure| 1047645-82-8 同义名 : LAE002 hydrochloride;GSK2110183 hydrochloride;GSK2110183B;Afuresertib (hydrochloride);Afuresertib hydrochloride
CAS号 : 1047645-82-8
货号 : A135971
分子式 : C18H18Cl3FN4OS
纯度 : 99%+
分子量 : 463.784
MDL号 : MFCD28167824
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:1个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(226.4 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Akt (protein kinase B) is a master regulator of cell survival in response to growth factors. In human cancers, Akt plays a pivotal role in cell growth, apoptosis inhibition, protein synthesis, and glucose and fatty acid metabolism by phosphorylating its substrates, including CDK2, FOXO, GSK-3beta, S6 kinase, and mTOR[2]. Afuresertib, a thiophenecarboxamide derivative, is a catalytic ATP‐competitive inhibitor of AKT1, AKT2, AKT3 with Ki values of 0.08 nM, 2 nM, and 2.6 nM[3]. Afuresertib, an ATP‐competitive specific Akt inhibitor, exerted tumor‐specific effects on MPM cells. Afuresertib significantly increased caspase‐3 and caspase‐7 activities and apoptotic cell number among ACC-MESO-4 and MSTO-211H cells. Moreover, Afuresertib strongly arrested the cell cycle in the G1 phase[2]. Cells treated with Afuresertib show decreased phosphorylation of several substrates downstream of AKT. Afuresertib at 5 μmol/L for 24h clearly suppressed the migration of ACC-MESO-4 and MSTO-211H cells[3]. In a phase IIa study of Afuresertib, patients were treated with oral Afuresertib (125 mg/d) for over 28 weeks, it was showed that Afuresertib had clinical activity in some patients with newly diagnosed and advanced LCH[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.16mL

0.43mL

0.22mL

10.78mL

2.16mL

1.08mL

21.56mL

4.31mL

2.16mL
参考文献

[1]Dumble M, Crouthamel MC, et al. Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. PLoS One. 2014 Jun 30;9(6):e100880.

[2]Yamaji M, Ota A, Wahiduzzaman M, Karnan S, Hyodo T, Konishi H, Tsuzuki S, Hosokawa Y, Haniuda M. Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27. PMID: 28960945; PMCID: PMC5673922.

[3]Dumble M, Crouthamel MC, Zhang SY, Schaber M, Levy D, Robell K, Liu Q, Figueroa DJ, Minthorn EA, Seefeld MA, Rouse MB, Rabindran SK, Heerding DA, Kumar R. Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. PLoS One. 2014 Jun 30;9(6):e100880. doi: 10.1371/journal.pone.0100880. PMID: 24978597; PMCID: PMC4076210.

[4]Arceci RJ, Allen CE, Dunkel IJ, Jacobsen E, Whitlock J, Vassallo R, Morris SR, Portnoy A, Reedy BA, Smith DA, Noble R, Murnane A, Cornfeld M, Rodriguez-Galindo C, Heaney ML, McClain K, Vaiselbuh S. A phase IIa study of afuresertib, an oral pan-AKT inhibitor, in patients with Langerhans cell histiocytosis. Pediatr Blood Cancer. 2017 May;64(5). doi: 10.1002/pbc.26325. Epub 2016 Nov 2. PMID: 27804235.