MI-538是menin和MLL融合蛋白相互作用的抑制剂；IC₅₀值为21 nM。

MI-538 is an inhibitor of the interaction between menin and MLL fusion proteins with an IC 50 of 21 nM.

Solid

IC50 : 21 nM (menin and MLL interaction); Kd: 6.5 nM (menin)

MI-538 inhibits the proliferation of MLL leukemia cells with a GI50 of 83 nM. MI-538 shows no effect (up to 6 μM) on growth of the control cell lines HL-60 and HM-2, which do not harbor MLL translocations, demonstrating good selectivity toward MLL fusion protein transformed cells. MI-538 binds to menin with low nanomolar affinity (Kd=6.5 nM). Its potent cellular activity originates from the improved binding affinity to menin and possibly increased cell membrane permeability. Treatment with MI-538 results in strong down regulation of expression of Hoxa9 and Meis1 genes. About 100 nM 27 was sufficient to reduce by ~50% Hoxa9 expression in MLL-AF9 cells, and even more pronounced effect was seen on Meis1 expression. has not independently confirmed the accuracy of these methods. They are for reference o

Treatment with MI-538 results in a pronounced, about 80%, reduction in the MV4;11 tumor volume, without causing substantial signs of toxicity reflected by less than 10% reduction of the body weight. MI-538 demonstrates markedly improved exposure (area under the curve, AUC, values), Cmax (maximum compound concentration) in the blood plasma, and the lowest value of clearance. The half-life of MI-538 is about 1.6 h. MI-538 has also high oral bioavailability (~50%). has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Borkin D, et al. Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein-Protein Interaction between Menin and Mixed Lineage Leukemia (MLL). J Med Chem. 2016 Feb 11;59(3):892-913.

In Vitro: DMSO : 100 mg/mL (176.49 mM; Need ultrasonic)配制储备液