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| 10mg |
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| Targets |
MI-136 targets the menin-MLL (mixed-lineage leukemia) protein-protein interaction (PPI), with an IC50 of 31 nM and a Kd of 23.6 nM. Menin is a scaffold protein that interacts with MLL1 and MLL2 to regulate the expression of genes involved in hematopoiesis and cancer. By inhibiting this interaction, MI-136 disrupts the transcriptional complex and modulates downstream gene expression.
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| 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].
In vitro, MI-136 potently inhibits the menin-MLL interaction. It has been shown to inhibit DHT-induced expression of androgen receptor (AR) target genes in AR-positive cell lines such as VCaP, LNCaP, and 22RV1. Treatment with MI-136 also inhibits the expression of genes bound by ASH2L after AR stimulation and induces apoptosis in VCaP cells. |
| 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].
In vivo, MI-136 has been investigated for its potential in treating castration-resistant tumors. By inhibiting the menin-MLL interaction, it can modulate the AR signaling pathway, which is a key driver of prostate cancer. It is being studied as a potential therapeutic agent for androgen receptor-dependent diseases, such as prostate cancer. |
| Enzyme Assay |
The binding affinity of MI-136 to the menin-MLL interaction is typically evaluated in a biochemical assay. Menin protein and a labeled MLL peptide are incubated with varying concentrations of MI-136. The displacement of the peptide is measured using a fluorescence polarization (FP) or AlphaScreen assay. The IC50 and Kd values are calculated from the resulting binding curves.
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| 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. Cellular assays are performed using AR-positive prostate cancer cell lines like VCaP, LNCaP, and 22RV1. Cells are treated with MI-136, and the expression of AR target genes is measured by qPCR. The compound's effects on cell proliferation and apoptosis are assessed using standard assays like CellTiter-Glo and flow cytometry (Annexin V staining). |
| 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. The in vivo efficacy of MI-136 is evaluated in mouse xenograft models of prostate cancer. Mice bearing tumors derived from AR-positive cell lines are treated with MI-136. Tumor volume is measured regularly, and the antitumor activity is assessed by comparing tumor growth in treated and control groups. The compound can be administered orally or intraperitoneally. |
| ADME/Pharmacokinetics |
MI-136 has a molecular weight of 470.51 g/mol and a chemical formula of C23H21F3N6S. It is soluble in DMSO and ethanol but insoluble in water. As a small molecule, it is expected to have good oral bioavailability. Pharmacokinetic studies would involve measuring plasma concentrations to determine its half-life and exposure.
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| Toxicity/Toxicokinetics |
MI-136 is generally well-tolerated in preclinical studies. As a menin-MLL inhibitor, its toxicity is primarily related to its on-target effects on normal hematopoiesis and other cellular processes. The safety profile is carefully evaluated in toxicology studies to determine the therapeutic window.
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| References |
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| Additional Infomation |
MI-136 is a valuable research tool for studying the role of the menin-MLL interaction in cancer and other diseases. It has been shown to be effective in preclinical models of castration-resistant prostate cancer and is being investigated as a potential therapeutic strategy for this disease.
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| Molecular Formula |
C23H21F3N6S
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|---|---|
| Molecular Weight |
470.513252973557
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| Exact Mass |
470.15
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| CAS # |
1628316-74-4
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| PubChem CID |
86297077
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| Appearance |
White to off-white solid powder
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| LogP |
5.236
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
721
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CN(CCC1NC2=C3C=C(SC3=NC=N2)CC(F)(F)F)CC4=CC5=C(C=C4)NC(=C5)C#N
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| InChi Key |
PSOJDGBGVBEYJX-UHFFFAOYSA-N
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| 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)
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| 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
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~110 mg/mL (~233.79 mM)
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| 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. View More
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. |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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