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BLU-782

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Chemical Structure| 2141955-96-4 同义名 : Activin Receptor-like Kinase 2 Inhibitor 1;Fidrisertib;ALK2-IN-1
CAS号 : 2141955-96-4
货号 : A1177054
分子式 : C31H42N6O4
纯度 : 99%+
分子量 : 562.703
MDL号 : MFCD32062780
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 85 mg/mL(151.06 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 Fibrodysplasia ossificans progressive (FOP) is most commonly caused by a highly recurrent autosomal dominant gain-of-function missense mutation in the ACVR1/ALK2 gene which encodes the activin receptor type Ia[1]. BLU-782 is an oral precision therapy specifically designed to selectively target mutant ALK2 with IC50 value of less than 10 nM[2]. BLU-782 was derived from Blueprint Medicines' proprietary compound library and optimized via structure-guided medicinal chemistry for potent and selective targeting of mutant ALK2. BLU-782 demonstrated exquisite selectivity for R206H mutant ALK2 in cellular assays, while sparing closely related anti-targets including ALK1, ALK3, and ALK6. Additionally, BLU-782 potently inhibited mutant ALK2 in vitro, regardless of the activating ligand, including Activin A, Activin B and BMP6. In vivo studies in a conditional knock-in ALK2R206H transgenic mouse model showed BLU-782 prevented the formation of injury-induced HO and edema, as measured by micro computed tomography and magnetic resonance imaging. In addition, BLU-782 prevented the formation of surgery-induced HO following fibular osteotomy surgery in ALK2R206Hmice[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.78mL

0.36mL

0.18mL

8.89mL

1.78mL

0.89mL

17.77mL

3.55mL

1.78mL
参考文献

[1]Wentworth K L, Masharani U, Hsiao E C, et al. Therapeutic advances for blocking heterotopic ossification in fibrodysplasia ossificans progressiva. British Journal of Clinical Pharmacology, 2019, 85(6): 1180-1187

[2]Natasja Brooijmans, et al. Inhibitors of activin receptor-like kinase. WO2017181117A1

[3]Blueprint Medicines Presents Foundational Preclinical Data Supporting the Development of BLU-782, a Highly Selective ALK2 Inhibitor, for the Treatment of Patients with Fibrodysplasia Ossificans Progressiva