AP232 dihydrochloride

AP232 dihydrochloride is a selective U2AF1-UHM Inhibitor with an IC₅₀ of 7.96 μM. AP232 dihydrochloride exhibits 2.8-24-fold selectivity against other UHM-containing proteins. AP232 dihydrochloride exerts anti-leukemia activity and shows higher activities in cell lines carrying splicing factor mutations. AP232 dihydrochloride can induce leukemia cells G2/M and G1 arrest, impair lysosome acidification, and inhibit autophagy. AP232 dihydrochloride can be used for the research of cancer, such as Leukemia ^[1].

In Vitro, AP232 dihydrochloride inhibits the U2 auxiliary factor homology motif of U2AF1 (U2AF1-UHM) with an IC₅₀ of 7.96 μM and exhibits 2.8-24-fold selectivity against other UHM-containing proteins (RBM39-UHM, SPF45-UHM, PUF60-UHM, U2AF2-UHM)^[1]. AP232 (40 μM) dihydrochloride stabilizes endogenous full-length U2AF1 and reduces its sensitivity to Pronase in K562 cell^[1]. AP232 (72 h) dihydrochloride inhibits cell growth in 6 leukemia cell lines (MV4-11, NKM-1, K562, MOLM13, HNT-34, MONO-MAC1)^[1]. AP232 (5-30 μM, 24-48 h) dihydrochloride disrupts the cell cycle of leukemia cells^[1]. AP232 (20 μM, 2 h) dihydrochloride reduces the proportion of functional lysosomes in NKM-1, K562, and MV4-11 cells^[1]. AP232 (10-30 μM, 48 h) dihydrochloride inhibits autophagy in NKM-1 and K562 cells^[1].

References:
[1]. Amol D, et al.. Discovery of the U2AF1-UHM Inhibitor That Possesses AntiLeukemia Activity In Vit. ACS Med. Chem. Lett. 2025, 16, 10, 2015-2021.