MI-538

小分子

MI-538

M651225-5mg

5mg

≥98%

-20°C储存

超低温冰袋运输

MI-538 is an inhibitor of the interaction between menin and MLL fusion proteins with an IC 50 of 21 nM. In Vitro MI-538 inhibits the proliferation of MLL leukemia cells with a GI 50 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 (K d =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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo 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%) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Form:Solid IC50& Target:IC50 : 21 nM (menin and MLL interaction),Kd: 6.5 nM (menin)

MI-538 是 Menin 与 MLL 融合蛋白相互作用的抑制剂，其 IC 50 为 21 nM。

1857417-10-7

C27H25F3N8OS

566.60 g/mol

FC(F)(F)CC(S1)=CC2=C1N=CN=C2NC3CCN(CC4=C(O)C=C(N(CC5=CNN=C5)C(C#N)=C6)C6=C4)CC3

DMSO : 100 mg/mL (176.49 mM; Need ultrasonic)