MI-136 inhibits DHT-induced expression of androgen receptor (AR) target genes. Target: androgen receptorin vitro: 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 were bound to ASH2L after AR stimulation. Treatment with MI-136 induces apoptosis of VCaP cells as evidenced by PARP (cPARP) cleavage. Furthermore, treatment with MI-136 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]in vivo: Treatment of VCaP tumor-bearing mice with MI-136 (40mg/kg) led to a modest but significant reduction in tumor volume with no effect on mouse body weight. [1]
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