Molecular Formula | C23H21F3N6S |
Molar Mass | 470.51 |
Density | 1.45±0.1 g/cm3(Predicted) |
Boling Point | 654.9±55.0 °C(Predicted) |
Solubility | Soluble in DMSO |
pKa | 14.20±0.30(Predicted) |
Storage Condition | -20℃ |
Use | MI-136 is an inhibitor of menin-MLL (PPI) protein interaction with an IC50 value of 31 nM and a Kd value of 23.6 nM. MI-136 can inhibit AR signaling pathway and has the potential to be used in castration-resistant tumors. |
Target | Androgen Receptor |
In vitro study | AR positive cell lines such as VCaP, LNCaP and 22RV1 are MI-136 sensitive, and MI-136 treatment can inhibit the expression of genes binding to ASH2L and induce apoptosis of VCaP cells after AR stimulation, DHT-induced cell proliferation was prevented in AR-dependent cell lines (LNCaP and VCaP). MI-136 has an effect on cell proliferation similar to that of MDV-310 (a second-generation FDA-approved antiandrogen for the treatment of refractory prostate cancer) |
In vivo study | Mice bearing VCaP tumors were administered MI-136(40mg/kg), and the tumor volume was significantly reduced, but there was no effect on the body weight of the mice. |
Reference Show more | 1. Dmitry Borkin, 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):892-913.2. Rohit Malik, et al. Targeting the MLL complex in castration-resistant prostate cancer. Nat Med. 2015 Apr;21(4):344-52. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.125 ml | 10.627 ml | 21.253 ml |
5 mM | 0.425 ml | 2.125 ml | 4.251 ml |
10 mM | 0.213 ml | 1.063 ml | 2.125 ml |
5 mM | 0.043 ml | 0.213 ml | 0.425 ml |
biological activity | MI-136 inhibit the expression of androgen receptor (AR) targeting genes induced by DHT. |
target | TargetValue Menin-MLL interaction () |
Target | Value |
in vitro study | AR-positive cell lines such as VCaP, LNCaP and 22RV1 are sensitive to MI-136. MI-136 treatment will inhibit the expression of genes bound to ASH2L after AR stimulation, induce apoptosis of VCaP cells, and prevent DHT-induced cell proliferation in AR-dependent cell lines (LNCaP and VCaP). The effect of MI-136 on cell proliferation is similar to that of MDV-310 (a second-generation FDA-certified antiandrogen drug for the treatment of refractory prostate cancer) |
in vivo study | MI-136(40 mg/kg) was applied to mice carrying VCaP tumor, and the tumor volume was significantly reduced, but it had no effect on the weight of mice. |