abc-dlbcl

Mepazine (Pecazine) is a potent and selective inhibitor of MALT1, inhibiting GSTMALT1 full length and GSTMALT1 325-760 with IC50s of 0.83 μM and 0.42 μM, respectively. Mepazine enhances apoptosis and impacts cell viability.

BHA536 is an orally effective inhibitor of PKCα β and the NF-kB signaling pathway. This compound inhibits the proliferation of ABC DLBCL cells harboring CD79 mutations by causing cell cycle arrest in the G1 phase and induces apoptosis in TMD8 cells. Additionally, BHA536 exhibits antitumor activity in mice.

Emavusertib Maleate (also known as CA-4948) is a potent inhibitor of IRAK4 FLT3, demonstrating antitumor activity. In ABC DLBCL and AML cell lines, CA-4948 exhibited strong cellular activity. It showed moderate to high selectivity in a test against 329 kinases and demonstrated good oral bioavailability in ADME and PK profiles, with effective absorption in mice, rats, and dogs. In relevant tumor models, CA-4948 achieved over 90% tumor growth inhibition and showed excellent correlation with in vivo PD modulation.

Emavusertib Tosylate (also known as CA-4948) is a potent inhibitor of IRAK4 FLT3 with demonstrated antitumor activity. In cell lines such as ABC DLBCL and AML, CA-4948 exhibits strong cellular efficacy. Among 329 evaluated kinases, it shows medium to high selectivity. The compound has excellent oral bioavailability and favorable pharmacokinetic properties in ADME and PK profiles. In preclinical models involving mice, rats, and dogs, CA-4948 demonstrated good oral bioavailability and displayed over 90% tumor growth inhibition in relevant tumor models, correlating well with in vivo pharmacodynamic regulation.

Emavusertib Mesylate (also known as CA-4948) is a potent inhibitor of IRAK4 and FLT3, demonstrating antitumor activity. In cell lines of ABC DLBCL and AML, CA-4948 shows significant cellular activity. Moreover, it exhibits moderate to high selectivity in screening assays of 329 kinases and has impressive pharmacokinetic and pharmacodynamic profiles (ADME and PK), with good oral bioavailability in mice, rats, and dogs. In pertinent tumor models, CA-4948 achieves over 90% tumor growth inhibition and shows excellent correlation with in vivo PD modulation.

Emavusertib Phosphate (also known as CA-4948) is a potent inhibitor of IRAK4 and FLT3, exhibiting antitumor activity. In ABC DLBCL and AML cell lines, it demonstrates significant cellular efficacy. Furthermore, CA-4948 shows moderate to high selectivity across a panel of 329 kinases and possesses favorable ADME and PK profiles, including good oral bioavailability in mice, rats, and dogs. It achieves over 90% tumor growth inhibition in relevant tumor models and correlates excellently with in vivo PD modulation.

iNUB is a NEMO-Ub binding inhibitor. iNUB inhibits TNFα induced NF-κB signaling and has selectively toxic to IKK/NF-κB dependent ABC-DLBCL.

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].

IRAK4-IN-7 (CA-4948) is a selective and potent IRAK4 kinase inhibitor with in vivo activity in a TLR4-induced cytokine release model.

(R)-MLT-985 (compound 11) is a potent MALT1 protease inhibitor (IC50: 3 nM) and has an IC50 value of 20 nM for MALT1-dependent IL-2 in Jurkat cells. Additionally, (R)-MLT-985 inhibits the growth and aberrant CARD11 BCL10 MALT1 complex signaling in ABC-DLBCL cells.

IRAK4-IN-15 is a selective and potent IRAK4 inhibitor (IC50: 0.002 μM) with good human PK prediction and low intrinsic clearance.IRAK4-IN-15 in combination with Acalabrutinib exhibited potent synergistic in vitro activity against MyD88 CD79 double mutant ABC-DLBCL.

IRAK4-IN-14 is a selective, potent, orally active IRAK4 inhibitor (IC50: 0.003 μM) with favorable PK parameters in rats and mice. effect.

KIN-8194 is a dual inhibitor of HCK and BTK, effective when administered orally, displaying IC 50 values of 0.915 nM for HCK and <0.495 nM for BTK. It inhibits growth and disrupts integrin-mediated adhesion in BTKi-resistant mantle cell lymphoma (MCL). Additionally, KIN-8194 has shown efficacy in overcoming ibrutinib resistance, enhancing survival in TMD-8 ABC DLBCL xenografted mice [1] [2].

SGR-1505, an orally active MALT1 allosteric inhibitor, reduces MALT1 enzymatic activity and demonstrates anti-proliferative effects in both BTK inhibitor (BTKi)-sensitive and BTKi-resistant activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL) cell lines. SGR-1505 is applicable for B-cell lymphoma research [1].