A 83-01 (ALK5抑制剂) (RPM0008)

体外活性/In vitro:
1.用A 83-01（0.03-10 μM）和TGF-β（1 ng/mL）处理野生型水貂肺上皮细胞Mv1Lu 48 h，Coulter counter检测细胞增殖。A 83-01以剂量依赖的方式阻止TGF-β对Mv1Lu细胞生长的抑制。[1]
2.用A 83-01（1-10 μM）处理小鼠卵巢癌细胞HM-1 30 min，随后用TGF-β（1-10 ng/mL）处理60 min，Western Blot检测靶点蛋白表达水平。添加TGF-β1增加了pSmad3的表达，A 83-01抑制了TGF-β的上调。[2]

体内活性/In vivo:
1.将A 83-01（150 μg/只）腹腔注射给HM-1癌症腹膜扩散的B6C3F1小鼠模型，每周三次，持续四周，检测体内抗肿瘤活性。A 83-01治疗组的腹水形成往往较慢，A 83-01显著提高了小鼠的存活率。[2]
2.将A 83-01（10 mg/kg）腹腔注射给Nkx2.5 enh-Cre/mTmG小鼠，每天一次，持续七天，研究在心肌损伤中的作用。A 83-01治疗在基线和心肌损伤后显著增加了Nkx2.5+心肌成肌细胞的数量，导致新形成的心肌细胞增加，A 83-01治疗显著改善了心室弹性和卒中功，从而改善了损伤后的收缩能力。[3]

细胞实验/Cell Research:
HM-1 cells are seeded into a 96-well plate and are incubated for 18 hr. A-83-01 (1 μM) or vehicle are then added for 12 hr followed by the addition of TGF-β1 (1 ng/mL) or vehicle for 60 hr. The number of viable cells in each well is examined using the WST-1 assay following the manufacturer's instructions.

ALK5: 12 nM, ALK4: 45 nM, ALK7: 7.5 nM