MLT-231, a potent and highly selective allosteric MALT1 inhibitor, has an IC50 of 9 nM and specifically inhibits endogenous BCL10 cleavage with an IC50 of 160 nM. It exhibits antitumor activity in an ABC-DLBCL type xenograft mouse model[1].

MLT-231 (19.5-10000 nM) inhibits OCI-Ly3 cell proliferation and, at concentrations of 50-5000 nM for 24 hours, causes accumulation of the uncleaved substrates CYLD, BCL10, and RELB, while suppressing the NF-κB target gene IRF4[1].

MLT-231 (10-100 mg/kg; p.o.; bid schedule for 2 weeks) demonstrates in vivo efficacy in the ABC-DLBCL xenograft model[1]. MLT-231 (1 mg/kg; i.v.; BALB/c mice) treatment shows a CL of 11 mL/min/kg, t1/2 of 1.9 hours, and Vss of 1.5 L/kg[1]. In Sprague-Dawley rats, MLT-231 (1 mg/kg; i.v.) shows a CL of 41 mL/min/kg, t1/2 of 3.2 hours, and Vss of 9.4 L/kg[1]. MLT-231 (3 mg/kg; p.o.; BALB/c mice) treatment reveals an AUC0-24 of 3096 nM/h, Cmax of 549 nM, and F of 99%[1]. In Sprague-Dawley rats, MLT-231 (3 mg/kg; p.o.) shows an AUC0-24 of 547 nM/h, Cmax of 46 nM, and F of 61%[1].