MI136 是menin-MLL(PPI) 蛋白互作的抑制剂，其IC50值为31 nM，Kd值为23.6 nM。它可抑制 DHT 诱导的雄激素受体 (AR) 靶基因的表达，有用于去势抵抗性肿瘤的潜能。

MI-136 inhibits expression of androgen receptor (AR) target genes that DHT induced.

MI-136, a variant of a previously described inhibitor that can specifically inhibit the menin-MLL interaction. AR positive cell lines such as VCaP, LNCaP and 22RV1 are sensitive to MI-136. Treatment with MI-136 also inhibits the expression of genes that are bound to ASH2L after AR stimulation. Treatment with MI-136 induces apoptosis of VCaP cells as evidenced by PARP (cPARP) cleavage and blocks DHT-induced cell proliferation in AR-dependent cell lines (LNCaP and VCaP). The effect of MI-136 on cell proliferation is similar to MDV-3100, a second-generation FDA-approved anti-androgen for patients with refractory prostate cancer[1].

Treatment of VCaP tumor-bearing mice with MI-136 (40 mg/kg) leads to a modest but significant reduction in tumor volume with no effect on mouse body weight[1].

HSP90 binding, ATPase, and selectivity profiling assays: The potency of HSP90 inhibitors for HSP90α, HSP90β, and Grp94 is determined by AlphaScreen competition binding assays, and activity against TRAP-1 is assessed by an ATPase assay.

To assess the effect of MI-136 on AR signaling, VCaP cells are treated with DMSO or 5 μM MI-136 for 48 hours. Cells are serum starved by replacing the media with DMEM containing 5% charcoal-striped serum and MI-136 for 48 hrs. Cells are then stimulated with 10 nM DHT for 12 hrs and RNA is isolated and processed for expression microarrays. (Only for Reference)

1628316-74-4

C23H21F3N6S

470.52

Ethanol:87 mg/mL (184.9 mM)
H2O:<1 mgml
DMSO:87 mg/mL (184.9 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years