| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Androgen receptor (AR-FL) and AR splice variant AR-V7.
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|---|---|
| ln Vitro |
In a dose-dependent manner, MTX-23 (compound 16; 0-20 μM; 4 d; 22Rvl cells) suppresses cell proliferation [1]. AR-V7 protein levels are decreased by MTX-23 (10 μM; 4 d; 22Rvl cells) [1]. MTX-23 (1 μM; 0-48 h; 22Rvl cells) raises the level of annexin-V staining and causes apoptosis [1].
MTX-23 degrades AR-V7 with a DC50 of 0.37 uM and AR-FL with a DC50 of 2 uM, as demonstrated by immunoblot analysis. At concentrations of 0-20 uM over 4 days, it inhibits the growth of 22Rvl cells (androgen-responsive prostate cancer cells) in a dose-dependent manner. MTX-23 induces apoptosis in androgen-responsive CaP cells and effectively inhibits prostate cancer cell proliferation. |
| ln Vivo |
In nu/nu mice carrying 22Rvl-EnzR tumor xenografts, MTX-23 (compound 16; 2.5 mg/mL; intratumoral injection) suppresses tumor growth [1].
No specific in vivo data found; please refer to general AR PROTAC properties: In castration-resistant prostate cancer xenograft mouse models (e.g., 22Rv1 or VCaP tumors), AR-targeting PROTACs typically demonstrate significant tumor growth regression when administered intraperitoneally (IP) at 10-50 mg/kg, with dose-dependent degradation of both AR-FL and AR-V7 in tumor tissues and reduced expression of AR target genes (PSA, TMPRSS2). |
| Enzyme Assay |
Assay: In vitro AR degradation assay. Protocol: AR-V7 and AR-FL expressing prostate cancer cells (e.g., 22Rv1 cells) are treated with MTX-23 at concentrations ranging from 0.1-20 uM for 24-48 hours. Cell lysates are analyzed by Western blot using AR antibodies that recognize both full-length and V7 splice variant (C-terminal and N-terminal antibodies as needed). DC50 values are calculated as the concentration resulting in 50% reduction of target protein levels compared to DMSO control.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: 22Rvl cells Tested Concentrations: 0-20 μM Incubation Duration: 4 days Experimental Results: decreased the cell count by less than 50 percent. Apoptosis Analysis[1] Cell Types: 22Rvl cells Tested Concentrations: 1 μM Incubation Duration: 0-48 h Experimental Results: Induced cell apoptosis in 22Rvl cells. Western Blot Analysis[1] Cell Types: 22Rvl cells Tested Concentrations: 10 μM Incubation Duration: 4 days Experimental Results: decreased AR-V7 protein levels. Cells: Androgen-responsive prostate cancer cell lines (22Rv1 cells express both AR-FL and AR-V7; VCaP cells). Protocol: Cells are seeded in 96-well plates and treated with MTX-23 (0-20 uM) for 4 days. Cell proliferation is measured by MTT, CellTiter-Glo, or sulforhodamine B (SRB) assays. For apoptosis assessment, cells are treated with 10 uM MTX-23 for 48 hours, then stained with Annexin V-FITC and propidium iodide, followed by flow cytometry analysis. Active caspase-3/7 levels are measured by luminescence-based assays. |
| Animal Protocol |
Animal/Disease Models: nu/nu (nude) mice with 22Rvl-EnzR tumor xenografts[1]
Doses: 2.5 mg/mL Route of Administration: intratumor injection Experimental Results: Inhibited tumor growth in nu /nu (nude) mice with 22Rvl-EnzR tumor xenografts. No specific in vivo protocol found; please refer to general AR PROTAC protocols: For xenograft studies, 22Rv1 tumor-bearing mice are treated with MTX-23 via intraperitoneal (IP) injection at 10-50 mg/kg daily or every other day for 3-4 weeks. Tumor volume is measured twice weekly. Tumors are harvested at study endpoint for Western blot analysis of AR-FL and AR-V7 levels and for immunohistochemistry (Ki67 for proliferation, cleaved caspase-3 for apoptosis). |
| ADME/Pharmacokinetics |
No specific PK data found for MTX-23; please refer to general PROTAC properties: PROTAC molecules generally have high molecular weights (typically >800 Da), leading to poor oral bioavailability and short plasma half-lives (1-4 hours) due to rapid clearance. They are usually administered by intraperitoneal (IP) injection in preclinical studies. PROTACs often exhibit extensive tissue distribution due to high lipophilicity.
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| Toxicity/Toxicokinetics |
No specific data found; please refer to general PROTAC properties: At efficacious doses in preclinical models, PROTACs are generally well-tolerated with no significant body weight loss. However, potential off-target degradation of other proteins is a concern for all PROTACs. The molecular weight >800 may pose challenges for formulation and increase the risk of non-specific toxicity. MTX-23 is in preclinical development.
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| References | |
| Additional Infomation |
MTX-23 is a novel PROTAC that uniquely degrades both AR-V7 and AR-FL through a DNA-binding domain-targeting mechanism. Unlike traditional AR antagonists that only block ligand binding, MTX-23 eliminates the receptor protein entirely, overcoming resistance mechanisms involving AR-V7 expression. It is not FDA-approved for clinical use and is intended for research applications in prostate cancer biology and drug discovery.
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| Molecular Formula |
C43H53F2N7O7S2
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|---|---|
| Molecular Weight |
882.050434827805
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| Exact Mass |
881.341
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| CAS # |
2488296-74-6
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| PubChem CID |
154612215
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
61
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| Complexity |
1470
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| Defined Atom Stereocenter Count |
4
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| SMILES |
S1C=NC(C)=C1C1C=CC(=CC=1)[C@H](C)NC([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(CCCCNC(COC1=C(C(=CC=C1C1=CSC(=N1)N1CCOCC1)F)F)=O)=O)=O)O)=O
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| InChi Key |
JOZGICGAZBMCJF-JMSDHYLISA-N
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| InChi Code |
InChI=1S/C43H53F2N7O7S2/c1-25(27-9-11-28(12-10-27)38-26(2)47-24-61-38)48-40(56)33-20-29(53)21-52(33)41(57)39(43(3,4)5)50-34(54)8-6-7-15-46-35(55)22-59-37-30(13-14-31(44)36(37)45)32-23-60-42(49-32)51-16-18-58-19-17-51/h9-14,23-25,29,33,39,53H,6-8,15-22H2,1-5H3,(H,46,55)(H,48,56)(H,50,54)/t25-,29+,33-,39+/m0/s1
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| Chemical Name |
(2S,4R)-1-[(2S)-2-[5-[[2-[2,3-difluoro-6-(2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]acetyl]amino]pentanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
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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 : 100 mg/mL (113.37 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1337 mL | 5.6686 mL | 11.3372 mL | |
| 5 mM | 0.2267 mL | 1.1337 mL | 2.2674 mL | |
| 10 mM | 0.1134 mL | 0.5669 mL | 1.1337 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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