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ML347

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Chemical Structure| 1062368-49-3 同义名 : LDN 193719
CAS号 : 1062368-49-3
货号 : A616413
分子式 : C22H16N4O
纯度 : 98%
分子量 : 352.389
MDL号 : MFCD28099805
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 9 mg/mL(25.54 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
靶点

  • ALK1

    ALK1, IC50:46 nM

  • ALK2

    ALK2, IC50:32 nM
描述 The transforming growth factor (TGF)-β superfamily has been implicated into different physiological and pathological processes in a broad range of cell systems. The TGF-β receptor complex is composed of type I, type II and accessory receptors. TGF-β type I receptors have seven isoforms termed activin receptor-like kinases (ALKs) 1 - 7[2]. ML347 is a selective inhibitor of ALK1/2/3/6 with IC50 values of 46 nM, 32 nM, 10.8 μM and 9.83 μM, respectively[1]. In vitro, ML347 at dose of 50 nM dampened the GDF2-induced SMAD1/5 phosphorylation in MCF10A cells that express high levels of ALK2[3]. Utilizing rapid equilibrium dialysis, the protein binding of ML347 was determined in human, rat and mouse plasma shown that similar in all three species with ML347 displaying high plasma protein biding (Fu~0.01 - 0.015). ML347 was unstable to oxidative metabolism – possibly due to the labile methoxy group and therefore was predicted to display high clearance in human and mouse, and moderate to-high clearance in the rat[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.84mL

0.57mL

0.28mL

14.19mL

2.84mL

1.42mL

28.38mL

5.68mL

2.84mL
参考文献

[1]Engers DW, Frist AY, Lindsley CW, Hong CC, Hopkins CR. Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett. 2013;23(11):3248–3252

[2]Otten J, Schmitz L, Vettorazzi E, et al. Expression of TGF-β receptor ALK-5 has a negative impact on outcome of patients with acute myeloid leukemia. Leukemia, 2011, 25(2): 375-379.

[3]Varadaraj A, Patel P, Serrao A, et al. Epigenetic Regulation of GDF2 Suppresses Anoikis in Ovarian and Breast Epithelia. Neoplasia. 2015;17(11):826–838.