MLT-748

• CAT Number: I019318
• CAS Number: 1832578-30-9
• Molecular Formula: C19H19Cl2N9O3
• Molecular Weight: 492.32
• Purity: ≥95%
• Synonyms: 1-[2-chloro-7-[(1R,2R)-1,2-dimethoxypropyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(triazol-2-yl)pyridin-3-yl]urea
• InChI: InChI=1S/C19H19Cl2N9O3/c1-10(32-2)17(33-3)16-13(9-22-15-7-14(21)28-29(15)16)27-19(31)26-11-6-12(20)18(23-8-11)30-24-4-5-25-30/h4-10,17H,1-3H3,(H2,26,27,31)/t10-,17+/m1/s1
• InChIKey: XKQLNDPUQSZBJW-QGHHPUGFSA-N
• SMILES: CC(C(C1=C(C=NC2=CC(=NN21)Cl)NC(=O)NC3=CC(=C(N=C3)N4N=CC=N4)Cl)OC)OC

MLT-748 is a potent, selective and allosteric inhibitor of MALT1, binds MALT1 in the allosteric Trp580 pocket, with an IC50 of 5 nM[1].
MLT-748 reversibly binds to human mutant MALT1(329-728)-W580S (Kd, 13 nM) with affinity similar to that of the wild type MALT1(329-728) (Kd, 42 nM)[1].
MLT-748 (0-2 μM) stabilizes cellular MALT1-W580S, with an EC50 of 69 nM[1].
MLT-748 (2 μM, 24 hours) increases the phosphorylation of p65 and IκBα in MALT1mut/mut patient immortalized B cells[1].

Reference

[1]. Quancard J, et al. An allosteric MALT1 inhibitor is a molecular corrector rescuing function in an immunodeficient patient. Nat Chem Biol. 2019 Mar;15(3):304-313.
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