A 83-01 (ALK5 Inhibitor IV) is an inhibitor of the TGF-β type I receptors ALK5, ALK4, and ALK7 (IC50=12/45/7.5 nM). A 83-01 promotes the reprogramming of mouse fibroblasts into iPSCs. A 83-01 can be used in organoid cultures.

METHODS: Wild-type mink lung epithelial cells, Mv1Lu, were treated with A 83-01 (0.03-10 μM) and TGF-β (1 ng/mL) for 48 h, and cell proliferation was detected using a Coulter counter.
RESULTS: A 83-01 prevented the inhibition of Mv1Lu cell growth by TGF-β in a dose-dependent manner. [1]
METHODS: Mouse ovarian cancer cells HM-1 were treated with A 83-01 (1-10 μM) for 30 min, followed by treatment with TGF-β (1-10 ng/mL) for 60 min, and the expression levels of target proteins were detected using Western Blot.
RESULTS: The addition of TGF-β1 increased the expression of pSmad3, and A 83-01 inhibited the up-regulation of TGF-β. [2]

METHODS: To detect anti-tumor activity in vivo, A 83-01 (150 μg/each) was administered intraperitoneally three times a week for four weeks to a B6C3F1 mouse model of peritoneal spread of HM-1 cancer.
RESULTS: Ascites formation tended to be slower in the A 83-01-treated group, and A 83-01 significantly improved the survival rate of the mice. [2]
METHODS: To investigate the role in myocardial injury, A 83-01 (10 mg/kg) was administered intraperitoneally to Nkx2.5 enh-Cre/mTmG mice once daily for seven days.
RESULTS: A 83-01 treatment significantly increased the number of Nkx2.5+ myocardial myofibroblasts at baseline and after myocardial injury, leading to an increase in the number of newly formed myocardial cells. A 83-01 treatment significantly improved ventricular elasticity and stroke work, which led to an improvement of contractility after injury. [3]

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.