AR抑制剂(MI-136)

AR抑制剂(MI-136) - Names and Identifiers

Name	5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile
Synonyms	MI136 MI 136 MI-136 MI136) CS-2162 HY-19319 (MI 136 HY-19319 (MI 136 MI-136 HY-19319 (MI 136 MI136) 5-((4-((6-(2,2,2-Trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-in 5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile 5-[[4-[[6-(2,2,2-Trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]-1-piperidinyl]methyl]-1H-indole-2-carbonitrile 1H-Indole-2-carbonitrile, 5-[[4-[[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]-1-piperidinyl]methyl]-
CAS	1628316-74-4

AR抑制剂(MI-136) - Physico-chemical Properties

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.

AR抑制剂(MI-136) - Reference

Reference

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.

AR抑制剂(MI-136) - Preparation solution concentration reference

	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

Last Update：2024-01-02 23:10:35

AR抑制剂(MI-136) - Cell Experiment

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 10nM DHT for 12 hrs and RNA is isolated and processed for expression microarrays. (Only for Reference) Cell lines: VCaP cells

Last Update：2023-08-16 21:32:38

AR抑制剂(MI-136) - Reference Information

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.

Last Update：2024-04-09 02:00:01