| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 50mg | |||
| Other Sizes |
| Targets |
AA-CW236 targets O(6)-alkylguanine DNA methyltransferase (MGMT), a DNA repair protein that removes alkyl adducts from the O(6) position of guanine. MGMT is a suicide enzyme that transfers the alkyl group to its active site cysteine residue (Cys145), thereby repairing DNA damage. By covalently modifying Cys145, AA-CW236 irreversibly inactivates MGMT. This inhibition prevents the repair of DNA alkylation damage, which is a strategy to sensitize tumors to alkylating chemotherapeutic agents.
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| ln Vitro |
In vitro, AA-CW236 is a potent and selective non-pseudosubstrate inhibitor of MGMT with a KI of 24 nM. It covalently modifies the active site Cys145 of MGMT, leading to irreversible inhibition. The compound's low nanomolar potency makes it a highly effective tool for studying MGMT function and for sensitizing cancer cells to alkylating agents. In cell-based assays, AA-CW236 can deplete cellular MGMT activity, leading to increased sensitivity to DNA-alkylating drugs such as temozolomide.
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| ln Vivo |
In vivo, AA-CW236 has been studied for its potential to enhance the efficacy of alkylating chemotherapy. By inhibiting MGMT, the compound prevents the repair of DNA damage induced by chemotherapeutic agents like temozolomide and carmustine. This can lead to increased tumor cell death and improved treatment outcomes. However, specific in vivo data for AA-CW236 are limited in the available literature. The compound's cell-permeability makes it suitable for in vivo studies.
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| Enzyme Assay |
Non-cellular in vitro assays for AA-CW236 involve measuring its inhibition of purified recombinant MGMT enzyme. A typical protocol uses a fluorescent or radiolabeled substrate that is methylated by MGMT. The enzyme is incubated with varying concentrations of AA-CW236 for a specified time to allow for covalent modification. The remaining MGMT activity is then measured by adding the substrate and quantifying the product. The KI and kinact values are determined from the kinetic data.
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| Cell Assay |
Cellular assays for AA-CW236 are performed using cancer cell lines expressing MGMT, such as glioblastoma or colon cancer cells. Cells are treated with AA-CW236 at various concentrations for 1-24 hours. MGMT activity is measured in cell lysates using a substrate-based assay. Alternatively, the sensitization to alkylating agents is assessed by treating cells with AA-CW236 followed by an alkylating agent (e.g., temozolomide). Cell viability is measured using an MTT assay, and the potentiation of cytotoxicity is determined.
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| Animal Protocol |
In vivo animal studies for AA-CW236 are conducted in mouse xenograft models of MGMT-expressing tumors. Mice bearing tumors are treated with AA-CW236 (e.g., intraperitoneally at doses of 10-50 mg/kg) prior to or concurrently with an alkylating agent such as temozolomide. Tumor volume is measured over time. The combination therapy is compared to single-agent treatments to assess the enhancement of antitumor efficacy. Tumor tissue may be collected for analysis of MGMT activity and DNA damage markers.
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| ADME/Pharmacokinetics |
AA-CW236 has a molecular weight of not specified in the available literature but is soluble in DMSO at 25 mg/mL. For in vivo studies, it can be formulated in vehicles such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. The compound is cell-permeable, indicating it can cross biological membranes. Detailed pharmacokinetic parameters, such as half-life, bioavailability, and clearance, have not been fully reported. It is stored as a powder at -20°C for up to 3 years.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for AA-CW236 have not been extensively reported. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed when handling AA-CW236, including the use of personal protective equipment. No specific toxicity data, such as LD50 values, are available in the provided literature.
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| References |
Chemoproteomics-Enabled Discovery of a Potent and Selective Inhibitor of the DNA Repair Protein MGMT. Angew Chem Int Ed Engl. 2016 Feb 18;
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| Additional Infomation |
AA-CW236 is a novel, potent, and selective non-pseudosubstrate inhibitor of MGMT. It is a cell-permeable chloromethyl triazole (CMT) derivative that covalently modifies the active site Cys145 of MGMT. The compound is used as a research tool to study the role of MGMT in DNA repair and chemoresistance. It has potential applications in sensitizing tumors to alkylating chemotherapy. AA-CW236 is not a clinically approved drug and has not entered clinical trials. Its primary application is in academic and pharmaceutical research.
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| Molecular Formula |
C17H16CLF3N4O2
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|---|---|
| Molecular Weight |
400.7862
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| Exact Mass |
400.091
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| CAS # |
1869921-96-9
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| Related CAS # |
1869921-96-9
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| PubChem CID |
132470893
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
535.0±60.0 °C at 760 mmHg
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| Flash Point |
277.4±32.9 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.582
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| LogP |
3.46
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
480
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C(=NO1)C)CCN2C(=C(N=N2)C3=CC=C(C=C3)OC(F)(F)F)CCl
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| InChi Key |
MPDMMSRZEHOFPA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H16ClF3N4O2/c1-10-14(11(2)27-23-10)7-8-25-15(9-18)16(22-24-25)12-3-5-13(6-4-12)26-17(19,20)21/h3-6H,7-9H2,1-2H3
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| Chemical Name |
4-(2-(5-(Chloromethyl)-4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)ethyl)-3,5-dimethylisoxazole
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| Synonyms |
AA-CW-236AA-CW236 AACW-236AA-CW 236 AACW 236 AACW236
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.4951 mL | 12.4754 mL | 24.9507 mL | |
| 5 mM | 0.4990 mL | 2.4951 mL | 4.9901 mL | |
| 10 mM | 0.2495 mL | 1.2475 mL | 2.4951 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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