MLT-748
目录号 : GC65301MLT-748 is a potent, selective and allosteric inhibitor of MALT1 with IC50 of 5 nM, binding at the interface between the caspase and immunoglobulin (Ig3) domains by displacing Trp580 and locking the catalytic site in an inactive state.
Cas No.:1832578-30-9
Sample solution is provided at 25 µL, 10mM.
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MLT-748 is a potent, selective and allosteric inhibitor of MALT1 with IC50 of 5 nM, binding at the interface between the caspase and immunoglobulin (Ig3) domains by displacing Trp580 and locking the catalytic site in an inactive state.
MLT-748 binds MALT1 in the allosteric Trp580 pocket. MLT-748 binds and stabilizes mutant MALT1-W580S. Cleavage of MALT1 substrates is blocked by MLT-748 in B and T cells. MLT-748 rescues MALT1 function in patient MALT1mut/mut lymphocytes.[1]
[1] Quancard J, et al. Nat Chem Biol. 2019 Mar;15(3):304-313.
Cas No. | 1832578-30-9 | SDF | Download SDF |
分子式 | C19H19Cl2N9O3 | 分子量 | 492.32 |
溶解度 | DMSO : 200 mg/mL (406.24 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.0312 mL | 10.156 mL | 20.312 mL |
5 mM | 0.4062 mL | 2.0312 mL | 4.0624 mL |
10 mM | 0.2031 mL | 1.0156 mL | 2.0312 mL |
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Integrating knowledge of protein sequence with protein function for the prediction and validation of new MALT1 substrates
Comput Struct Biotechnol J 2022 Aug 19;20:4717-4732.PMID:36147669DOI:PMC9463181
We developed a bioinformatics-led substrate discovery workflow to expand the known substrate repertoire of MALT1. Our approach, termed GO-2-Substrates, integrates protein function information, including GO terms from known substrates, with protein sequences to rank substrate candidates by similarity. We applied GO-2-Substrates to MALT1, a paracaspase and master regulator of NF-κB signalling in adaptive immune responses. With only 12 known substrates, the evolutionarily conserved paracaspase functions and phenotypes of Malt1 -/- mice strongly implicate the existence of undiscovered substrates. We tested the ranked predictions from GO-2-Substrates of new MALT1 human substrates by co-expression of candidates transfected with the oncogenic constitutively active cIAP2-MALT1 fusion protein or CARD11/BCL10/MALT1 active signalosome. We identified seven new MALT1 substrates by the co-transfection screen: TANK, TAB3, CASP10, ZC3H12D, ZC3H12B, CILK1 and ILDR2. Using catalytically inactive cIAP2-MALT1 (Cys464Ala), a MALT1 inhibitor, MLT-748, and noncleavable P1-Arg to Ala mutant versions of each substrate in dual transfections, we validated the seven new substrates in vitro. We confirmed the cleavage of endogenous TANK and the RNase ZC3H12D in B cells by Western blotting and mining TAILS N-terminomics datasets, where we also uncovered evidence for these and 12 other candidate substrates by endogenous MALT1. Thus, protein function information improves substrate predictions. The new substrates and other high-ranked MALT1 candidate substrates should open new biological frontiers for further validation and exploration of the function of MALT1 within and beyond NF-κB regulation.