MI-136

Product NameMI-136
CAS1628316-74-4
MFC23H21F3N6S
MW470.51
EINECS
MOL File1628316-74-4.mol

Chemical Properties

Boiling point	654.9±55.0 °C(Predicted)
Density	1.45±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMF: 1 mg/ml; DMSO: 1 mg/ml; Ethanol: 10 mg/ml
form	A crystalline solid
pka	14.20±0.30(Predicted)
color	White to off-white

Usage And Synthesis

Description

MI-136 is an inhibitor of the menin-MLL interaction (IC₅₀ = 31 nM; K_d = 23.6 nM). By blocking MLL recruitment predominantly at the level of the menin-MLL interaction, it can inhibit androgen receptor (AR)-mediated transcription. At 40 mg/kg, MI-136 has been shown to block AR signaling, inhibiting the growth of castration-resistant tumors in mice.

Uses

MI-136 is an inhibitor of the menin-MLL protein-protein interaction (PPI), with an IC50 of 31 nM and a Kd of 23.6 nM. MI-136 shows to block AR signaling and has the potential for the study in castration-resistant tumors[1][2].

in vivo

MI-136 exhibits T_1/2 of 3.1 h after po administration^[1].
MI-136 (40 mg/kg, ip) leads to a significant decrease in the growth of castration-resistant VCaP tumors^[2].

Animal Model:	VCaP xenografts^[2].
Dosage:	40 mg/kg.
Administration:	Intraperitoneal injection, 5 days a week.
Result:	Led to a significant decrease in the growth of castration-resistant VCaP tumors compared to vehicle controls.

References

[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. DOI:10.1021/acs.jmedchem.5b01305
[2] Rohit Malik, et al. Targeting the MLL complex in castration-resistant prostate cancer. Nat Med. 2015 Apr;21(4):344-52. DOI:10.1038/nm.3830