Physicochemical Properties
| Molecular Formula | C23H21F3N6S |
| Molecular Weight | 470.513252973557 |
| Exact Mass | 470.15 |
| CAS # | 1628316-74-4 |
| PubChem CID | 86297077 |
| Appearance | White to off-white solid powder |
| LogP | 5.236 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 33 |
| Complexity | 721 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | PSOJDGBGVBEYJX-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C23H21F3N6S/c24-23(25,26)10-18-9-19-21(28-13-29-22(19)33-18)31-16-3-5-32(6-4-16)12-14-1-2-20-15(7-14)8-17(11-27)30-20/h1-2,7-9,13,16,30H,3-6,10,12H2,(H,28,29,31) |
| Chemical Name | 5-[[4-[[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]piperidin-1-yl]methyl]-1H-indole-2-carbonitrile |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | In LNCaP, VCaP, 22rv1, and PNT2 cells, the IC50 values of MI-136 (0-20) are 5.59 μM, 7.15 μM, 5.37 μM, and 19.76 μM [2]. |
| ln Vivo | Following oral administration of MI-136, the half-life is 3.1 hours [1]. The growth of castration-resistant VCaP tumors is significantly inhibited by MI-136 (40 mg/kg, intraperitoneally) [2]. |
| Cell Assay |
Cell proliferation assay [2] Cell Types: AR-positive cell lines, such as VCaP, LNCaP and 22RV1. Tested Concentrations: 0-20 μM. Incubation Duration: 24 hrs (hours). Experimental Results: Inhibition of cell proliferation. |
| Animal Protocol |
Animal/Disease Models: VCaP xenografts [2]. Doses: 40 mg/kg. Route of Administration: intraperitoneal (ip) injection, 5 days per week. Experimental Results: Growth of castration-resistant VCaP tumors was Dramatically diminished compared with vehicle controls. |
| References |
[1]. 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]. Targeting the MLL complex in castration-resistant prostate cancer. Nat Med. 2015 Apr;21(4):344-52. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~110 mg/mL (~233.79 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (5.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (5.84 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.75 mg/mL (5.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1254 mL | 10.6268 mL | 21.2535 mL | |
| 5 mM | 0.4251 mL | 2.1254 mL | 4.2507 mL | |
| 10 mM | 0.2125 mL | 1.0627 mL | 2.1254 mL |