MLT-231

• CAT Number: I045442
• CAS Number: 2682102-10-7
• Molecular Formula: C19H19ClF3N7O2
• Molecular Weight: 469.85
• Purity: ≥95%
• Synonyms: 1-[2-chloro-7-[(3S,5S)-3,5-dimethylmorpholin-4-yl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[2-(trifluoromethyl)pyridin-4-yl]urea
• InChI: InChI=1S/C19H19ClF3N7O2/c1-10-8-32-9-11(2)29(10)17-13(7-25-16-6-15(20)28-30(16)17)27-18(31)26-12-3-4-24-14(5-12)19(21,22)23/h3-7,10-11H,8-9H2,1-2H3,(H2,24,26,27,31)/t10-,11-/m0/s1
• InChIKey: BFPCFGGFGQMJQG-QWRGUYRKSA-N
• SMILES: CC1COCC(N1C2=C(C=NC3=CC(=NN32)Cl)NC(=O)NC4=CC(=NC=C4)C(F)(F)F)C

MLT-231 is a potent, highly selective allosteric MALT1 Inhibitor with an IC50 of 9 nM. MLT-231 specifically prevents endogenous BCL10 cleavage with IC50 of 160 nM. MLT-231 shows antitumor activity in an ABC-DLBCL type xenograft model in mouse[1].
MLT-231 (19.5-10000 nM) inhibits the proliferation of OCI-Ly3 cells. MLT-231 (50-5000 nM; 24 hours) leads to accumulation of the uncleaved form of its substrates CYLD, BCL10, and RELB while expression of the NF-κB target gene IRF4 is suppressed[1].
MLT-231 (10-100 mg/kg; p.o.; bid schedule for 2 weeks) displays in vivo efficacy in the ABC-DLBCL xenograft model[1].
MLT-231 (1 mg/kg; i.v.; BALB/c mice) treatment shows the CL, t1/2, and Vss are 11 mL/min/kg, 1.9 hours, and 1.5 L/kg, respectively[1].
MLT-231 (1 mg/kg; i.v.; Sprague-Dawley rats) treatment shows the CL, t1/2, and Vss are 41 mL/min/kg, 3.2 hours, and 9.4 L/kg, respectively[1].
MLT-231 (3 mg/kg; p.o.; BALB/c mice) treatment shows the AUC0-24, Cmax and F are 3096 nM/h, 549 nM, and 99%, respectively[1].
MLT-231 (3 mg/kg; p.o.; Sprague-Dawley rats) treatment shows the AUC0-24, Cmax and F are 547 nM/h, 46 nM, and 61%, respectively.

Reference

[1]. Pissot Soldermann C, et al. Discovery of Potent, Highly Selective, and In Vivo Efficacious, Allosteric MALT1 Inhibitors by Iterative Scaffold Morphing [published online ahead of print, 2020 Nov 30]. J Med Chem. 2020;10.1021/acs.jmedchem.0c01245.
 [Content Brief]