MALT1 Inhibitor

MALT1 inhibitor MI-2 is a MALT1 inhibitor (IC₅₀=5.84 μM). MALT1 inhibitor MI-2 binds directly to MALT1, irreversibly suppresses protease function and is accompanied by NF-κB reporter activity suppression, c-REL nuclear localization inhibition, and NF-κB target gene downregulation. MALT1 inhibitor MI-2 shows nontoxic to animals.

Safimaltib (JNJ-67856633) is an orally active, first-in-class, potent, selective and allosteric MALT1 protease inhibitor. Safimaltib in some cases lead to tumor stasis.

MLT-748 is a potent, selective and allosteric inhibitor of MALT1, binds MALT1 in the allosteric Trp580 pocket, with an IC₅₀ of 5 nM.

Mepazine (Pecazine) is a potent and selective MALT1 protease inhibitor with IC₅₀s of 0.83 and 0.42 μM for GSTMALT1 full length and GSTMALT1 325-760, respectively. Mepazine affects viability of ABC-DLBCL cells by enhancing apoptosis.

MLT-985 is a selective allosteric and orally active MALT1 inhibitor with an IC₅₀ value of 3 nM. MLT-985 can suppress cell growth and aberrant CARD11/BCL10/MALT1 complex signaling. MLT-985 can be used for the research of cancer, such as B cell malignancies.

SGR-1505 is an oral small molecule MALT1 inhibitor with anti-proliferative and antitumor activity.SGR-1505 inhibits MALT1 enzymatic activity to modulate NF-κB pathway gene expression.SGR-1505 induces modulation of cell cycle, DNA damage, and apoptosis-related genes in in vivo tumor samples.SGR-1505 exerts tumorostatic and regressive activity in ABC-DLBCL xenograft models.SGR-1505 can be used for the research of activated B cell-like diffuse large B cell lymphoma, non-Hodgkin B-cell lymphomas, chronic lymphocytic leukemia, and mature B cell neoplasms.

Mepazine hydrochloride (Pecazine hydrochloride) is a potent and selective MALT1 protease inhibitor with IC₅₀s of 0.83 and 0.42 μM for GSTMALT1 full length and GSTMALT1 325-760, respectively. Mepazine hydrochloride affects viability of ABC-DLBCL cells by enhancing apoptosis.

MLT-943 is a potent, selective and orally active MALT1 protease inhibitor. MLT-943 inhibits stimulated-IL-2 secretion in PBMC or in whole blood with a similar IC₅₀ across species (0.07-0.09 μM in PBMC, 0.6-0.8 μM in whole blood). MLT-943 has anti-inflammatory activities and can be used for FcgR-mediated inflammation research.

Z-VRPR-FMK is an irreversible MALT1 protein inhibitor. Z-VRPR-FMK inhibits the growth and invasion of diffuse large B-cell lymphoma by inhibiting MALT1-induced NF-κB activation and MMP expression.

MLT-747 is a potent, selective, allosteric inhibitor of MALT1, binds MALT1 in the allosteric Trp580 pocket, with an IC₅₀ of 14 nM.

INNO-220 is an orally active, CRBN-dependent molecular glue degrader targeting CK1α. INNO-220 induces cell cycle arrest at G0/G1 phase and triggers apoptosis by degrading CK1α. INNO-220 disrupts the assembly and function of the CARD11/BCL10/MALT1 complex, thereby inhibiting NF-κB signaling in stimulated T cells and lymphoma cells that harbor an activating mutation in CARD11. INNO-220 provides a new direction for lymphoma research.

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.

Mepazine acetate (Pecazine acetate) is a drug that has the activity to inhibit the protease activity of MALT1. Mepazine acetate is often used to study the role of MALT1 in biology. Treatment of mouse bone marrow precursor cells with mepazine acetate strongly inhibited RANK ligand (RANKL)-induced osteoclast formation. Mepazine acetate also inhibited the expression of multiple osteoclast markers such as TRAP, feline hepsin K, and calcitonin. The protective effect of mepazine acetate was not affected by MALT1 deficiency. The mechanism of action of mepazine acetate may involve MALT1-independent mechanisms, and this aspect needs to be considered in future studies.

MALT1-IN-11 (Example 151 in reference Patent) is a MALT1 protease inhibitor (IC₅₀ < 10 nM). MALT1-IN-11 inhibits IL10 secretion with an IC₅₀ of 10-100 nM. MALT1-IN-11 can be used for the research of cancer, autoimmune and inflammatory disorders.

Z-Val-Arg-Pro-DL-Arg-Fluoromethylketone TFA is an irreversible MALT1 protein inhibitor. Z-Val-Arg-Pro-DL-Arg-Fluoromethylketone TFA inhibits the growth and invasion of diffuse large B-cell lymphoma by inhibiting MALT1-induced NF-κB activation and MMP expression.

MALT1-IN-9 is a potent MALT1 protease inhibitor with a IC₅₀ of <500 nM in Raji MALT1-GloSensor cells. MALT1-IN-9 has anticancer effects (WO2021000855A1; Compound 5).

MALT1-IN-5 (compound 1) is a potent MALT1 protease inhibitor. MALT1-IN-5 can be used for cancer research.

(R)-MALT1-IN-7 (compound 142a) is a potent MALT1 protease inhibitor. (R)-MALT1-IN-7 has the potential for cancer research.

MALT1-IN-3 (compound 122) is a potent MALT1 protease inhibitor, with an IC₅₀ of 0.06 μM. MALT1-IN-3 has IC₅₀ of 0.14 and 0.13 μM for human IL6/IL10 in OCI-LY3 cells, respectively.

(R)-MLT-985 is the R configuration of MLT-985 (HY-142648). MLT-985 is a selective allosteric and orally active MALT1 inhibitor with an IC₅₀ value of 3 nM. MLT-985 can suppress cell growth and aberrant CARD11/BCL10/MALT1 complex signaling. MLT-985 can be used for the research of cancer, such as B cell malignancies.