Background:

(R)-GNE-140 is a potent lactate dehydrogenase A (LDHA) inhibitor, with IC50s of 3 nM and 5 nM for LDHA and LDHB, respectively; (R)-GNE-140 is 18-fold more potent than S enantiomer.

(R)-GNE-140 inhibits proliferation in 37 of 347 cancer cell lines tested at a potency cut off of 5 uM. (R)-GNE-140 shows inhibitory effect on two chondrosarcoma (bone) cancer cell lines that harbor IDH1 mutations, with IC50 of 0.8 uM[1].

(R)-GNE-140 (5 mg/kg) has high bioavailability in mice. At higher oral doses, ranging from 50 to 200 mg/kg, (R)-GNE-140 displays greater exposure.

参考文献:
[1]. Purkey HE, et al. Cell Active Hydroxylactam Inhibitors of Human Lactate Dehydrogenase with Oral Bioavailability in Mice. ACS Med Chem Lett. 2016 Aug 26;7(10):896-901.