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| Targets |
MYC (c-Myc) and the ubiquitin-proteasome system. As a molecular glue degrader, MYC degrader 1 TFA facilitates the interaction between MYC and an E3 ubiquitin ligase, leading to the ubiquitination and subsequent proteasomal degradation of the MYC protein.
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| ln Vitro |
In cell-free assays, the compound is a MYC degrader. Its activity is measured by its ability to reduce MYC protein levels in cells. It also restores pRB1 protein activity, which is a tumor suppressor that is often inactivated downstream of MYC. The specific biochemical IC50 is not provided. A general cell‑free protocol for assessing protein degradation is not available. Its activity is solely measured in cellular systems. A general cellular protocol for a MYC degrader: MYC-overexpressing cancer cells are seeded in 96-well plates and treated with serial dilutions of MYC degrader 1 (1 nM to 10 uM) for 48-72 hours. Cell viability is measured by CellTiter-Glo assay to determine the IC50. A general cell‑free protocol for assessing protein degradation is not available. Its activity is solely measured in cellular systems. A general cellular protocol for a MYC degrader: MYC-overexpressing cancer cells are seeded in 96-well plates and treated with serial dilutions of MYC degrader 1 TFA (1 nM to 10 uM) for 48-72 hours. Cell viability is measured by CellTiter-Glo assay to determine the IC50.
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| Cell Assay |
A general cellular protocol for MYC degradation: MYC-overexpressing cancer cells are treated with MYC degrader 1 TFA at concentrations of 0.1-10 uM for 6, 12, 24, and 48 hours. Cells are harvested and lysed. MYC protein levels are assessed by Western blot using an anti-c-Myc antibody. pRB1 protein levels and activity (as measured by its phosphorylation status) are also assessed.
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| Animal Protocol |
In vivo, MYC degrader 1 TFA (compound A80.2HCl) has demonstrated anti-tumor activity in animal models. It can be administered orally to mice bearing MYC-driven tumor xenografts, leading to significant tumor growth inhibition. The degradation of MYC in the tumor tissue is confirmed by Western blot and IHC. A general animal protocol for MYC degrader 1: Nude mice are subcutaneously implanted with MYC-overexpressing cancer cells. When tumors reach ~150 mm3, mice are randomized (n=8/group). The compound is formulated in a suitable vehicle and administered via oral gavage at doses of 10, 30, and 100 mg/kg once daily for 14-21 days. Tumor volume is measured twice weekly, and MYC levels in the tumor are assessed.
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| ADME/Pharmacokinetics |
General PK protocol for MYC degrader 1 TFA: The compound is described as orally available. A PK study would be performed in male Sprague-Dawley rats after oral (PO, 10 mg/kg) and intravenous (IV, 2 mg/kg) administration. Blood samples would be collected at various time points, and plasma concentrations would be quantified by LC-MS/MS to calculate key parameters.
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| Toxicity/Toxicokinetics |
General toxicity protocol for MYC degrader 1 TFA: A 14-day repeat-dose oral toxicity study would be performed in ICR mice. The compound would be administered at doses of 5, 15, and 40 mg/kg/day. Parameters would include clinical signs, body weight, food consumption, hematology, serum chemistry, and histopathology of major organs, especially the bone marrow and gastrointestinal tract.
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| References | |
| Additional Infomation |
MYC is considered one of the most difficult drug targets due to its lack of a defined binding pocket. MYC degrader 1 TFA (compound A80.2HCl) is an orally available MYC molecular glue degrader. The TFA (trifluoroacetate) salt form improves its solubility. This product is for research use only and has a purity of ≥98%. Its molecular weight is 740.09 g/mol.
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| Molecular Formula |
C34H32CLF6N5O5
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| Molecular Weight |
740.09
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| Appearance |
Solid powder
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 | 1.3512 mL | 6.7559 mL | 13.5119 mL | |
| 5 mM | 0.2702 mL | 1.3512 mL | 2.7024 mL | |
| 10 mM | 0.1351 mL | 0.6756 mL | 1.3512 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.
Products are for research use only; We do not sell to patients
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