MI-2

• CAT Number: I001086
• CAS Number: 1271738-62-5
• Molecular Formula: C₁₈H₂₅N₅S₂
• Molecular Weight: 375.55
• Purity: ≥95%
• Synonyms: 4-[4-(5,5-dimethyl-4H-1,3-thiazol-2-yl)piperazin-1-yl]-6-propylthieno[2,3-d]pyrimidine
• Target: Apoptosis
• Solubility: in DMSO > 10 mM
• Storage: Store at -20°C
• IC50: 446 ± 28 nM
• InChI: InChI=1S/C18H25N5S2/c1-4-5-13-10-14-15(20-12-21-16(14)24-13)22-6-8-23(9-7-22)17-19-11-18(2,3)25-17/h10,12H,4-9,11H2,1-3H3
• InChIKey: SRQYLNYQAPCPIR-UHFFFAOYSA-N
• SMILES: CCCC1=CC2=C(N=CN=C2S1)N3CCN(CC3)C4=NCC(S4)(C)C

MI-2（Cat No.:I001086）is a selective inhibitor of the histone methyltransferase G9a, which plays a critical role in the regulation of gene expression by methylating histone H3 at lysine 9 (H3K9). By targeting G9a, MI-2 disrupts the associated silencing of tumor suppressor genes and can induce apoptosis in cancer cells. This compound has demonstrated promising anti-cancer effects in preclinical studies, particularly in solid tumors and hematological malignancies with elevated G9a activity. MI-2’s ability to modulate epigenetic modifications positions it as a potential therapeutic agent for targeted cancer therapies.

Reference

[1]. Grembecka J, et al. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nature Chemical Biology (2012), 8(3), 277-284.
Abstract
Translocations involving the mixed lineage leukemia (MLL) gene result in human acute leukemias with very poor prognosis. The leukemogenic activity of MLL fusion proteins is critically dependent on their direct interaction with menin, a product of the multiple endocrine neoplasia (MEN1) gene. Here we present what are to our knowledge the first small-molecule inhibitors of the menin-MLL fusion protein interaction that specifically bind menin with nanomolar affinities. These compounds effectively reverse MLL fusion protein-mediated leukemic transformation by downregulating the expression of target genes required for MLL fusion protein oncogenic activity. They also selectively block proliferation and induce both apoptosis and differentiation of leukemia cells harboring MLL translocations. Identification of these compounds provides a new tool for better understanding MLL-mediated leukemogenesis and represents a new approach for studying the role of menin as an oncogenic cofactor of MLL fusion proteins. Our findings also highlight a new therapeutic strategy for aggressive leukemias with MLL rearrangements.