IKZF Family

TL4-12 is a selective inhibitor of MAP4K2 and GCK, demonstrating a dose-dependent ability to downregulate IKZF1 and BCL-6. This compound effectively inhibits cell proliferation in multiple myeloma with an IC50 of 37 nM, and it also induces apoptosis in cancerous cells. TL4-12 holds potential for overcoming resistance to immunomodulatory agents in the treatment of multiple myeloma.

KB528 is a selective inhibitor of the histone acetyltransferases p300 and CBP, demonstrating low nM IC50 values against these targets while sparing other members of the KAT family. This compound modulates the IRF4 transcriptional network, leading to decreased expression of key oncogenes such as IRF4, MYC, CAV2, and IGLL5, as well as reduced levels of IKZF3 protein. KB528 has been shown to effectively induce apoptosis in multiple myeloma cells, making it a valuable tool for research in multiple myeloma and related oncological studies.

PVTX-405 is a selective, orally bioavailable inhibitor targeting IKZF2, designed as a molecular glue degrader. With a DC50 of 0.7 nM and a Dmax of 91%, it enhances degradation efficiency while minimizing off-target effects, exhibiting an IC50 of 48 µM for hERG inhibition. PVTX-405 demonstrates significant antitumor activity by inhibiting the growth of MC38 tumors and shows improved efficacy when combined with immune checkpoint therapies, such as anti-PD1 or anti-LAG3, in mouse models.

PPACK dihydrochloride is a potent and selective irreversible inhibitor of thrombin. It serves as an alternative anticoagulant to lithium heparin for blood gas and electrolyte analyses in whole blood. Additionally, PPACK dihydrochloride inhibits plasminogen activator (rt-PA), preventing its binding to plasma protease inhibitors. This compound also reduces plasmin-induced endothelial permeability and morphological changes in bovine aortic endothelial cell monolayers, making it suitable for investigations in thrombosis-related research.

EM12-SO2F is a potent covalent inhibitor of the E3 ubiquitin ligase cereblon (CRBN), specifically binding to the histidine residue at position 353. This compound serves as a valuable chemical probe for studying CRBN-mediated pathways. EM12-SO2F effectively inhibits the lenalidomide-induced degradation of IKZF1 in MOLT4 cells, making it a useful tool for research in cancer biology and drug resistance.