Indisulam

Indisulam is a sulfonamide with anticancer activity.¹ In vitro, indisulam has antiproliferative effects on a wide range of human tumor lines with HCT116 colorectal being the most sensitive and NCI-H596 non-small cell lung cancer (NSCLC) the most resistant (IC₅₀s = 0.11 and 94 μg/ml, respectively). It increases the number of P388 murine leukemia cells in the G₁ phase of the cell cycle in a dose-dependent manner and exerts time-dependent cytotoxicity against HCT116 cells. In vivo, indisulam suppresses tumor growth and decreases tumor volume in murine HCT116, SW620, and HCT15 colorectal and LX-1 and PC9 lung cancer xenograft models. Indisulam induces proteasomal degradation of RNA binding motif protein 39 (RBM39) through association with the CUL4-DCAF15 E3 ubiquitin ligase in vitro.² It is also an inhibitor of carbonic anhydrase in H. pylori (K_i = 310-562 nM).³

1.Ozawa, Y., Sugi, N.H., Nagasu, T., et al.E7070, a novel sulphonamide agent with potent antitumour activity in vitro and in vivoEur. J. Cancer37(17)2275-2282(2001) 2.Han, T., Goralski, M., Gaskill, N., et al.Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15Science356(6336)(2017) 3.Nishimori, I., Vullo, D., Minakuchi, T., et al.Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pyloriBioorg. Med. Chem. Lett.16(8)2182-2188(2006)