| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
CARM1 (Coactivator‑Associated Arginine Methyltransferase 1).
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|---|---|
| ln Vitro |
In cell‑free biochemical assays, CARM1 degrader-1 hydrochloride degrades CARM1 with a DC₅0 (concentration for 50% degradation) of 8.1 nM. The compound inhibits the methylation of CARM1 substrates, including poly(A)-binding protein PABP1 and BGR1‑associated factor BAF155. As a result, it inhibits breast cancer cell migration. The molecular weight is 1316.14, and the molecular formula is C₇1H₉₉ClN12O₈S.
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| Enzyme Assay |
General cell‑free assay for CARM1 PROTAC ternary complex formation: Use an AlphaScreen or TR‑FRET assay to detect the interaction between CARM1 and the VHL E3 ligase in the presence of the degrader. Purify CARM1 (as part of a complex) and VHL‑elongin B‑elongin C complex. Incubate with varying concentrations of CARM1 degrader-1 hydrochloride (0.1 nM to 10 uM). Add donor and acceptor beads (or labeled antibodies). Measure the signal to calculate EC₅0 for ternary complex formation. Alternatively, assess CARM1 methylation activity using a methyltransferase assay with recombinant CARM1 and a substrate peptide (e.g., GST‑PABP1) in the presence of 3H‑SAM or by time‑resolved fluorescence after degrader treatment.
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| Cell Assay |
General cellular degradation protocol: Seed breast cancer cells (e.g., MCF‑7 or MDA‑MB‑231) that express CARM1 in 6‑well plates. Treat cells with CARM1 degrader-1 hydrochloride at concentrations of 0.1, 1, 5, 10, 20, 50, 100, 500, 1000 nM for 24‑48 hours. Harvest cells, lyse, and perform SDS‑PAGE and Western blot with anti‑CARM1 and anti‑GAPDH (loading control). Quantify band intensities to calculate DC₅0 and Dmax. For mechanistic studies, co‑treat with the proteasome inhibitor MG132 (10 uM, 4‑6 hours) to confirm proteasome‑dependent degradation. Assess cell migration using Transwell or wound‑healing assays. Assess methylation of CARM1 substrates (PABP1, BAF155) by immunoprecipitation followed by Western blot with anti‑asymmetric dimethyl arginine antibody. Assess cell viability using MTT or CellTiter‑Glo assay.
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| Animal Protocol |
General animal protocol for CARM1 degraders: Establish subcutaneous xenografts of CARM1‑dependent breast cancer cells (e.g., MDA‑MB‑231) in immunocompromised mice (nude or NOD/SCID). When tumors reach ~150 mm3, randomize mice (n=6‑8/group). Administer CARM1 degrader-1 hydrochloride via intraperitoneal injection at doses of 5‑25 mg/kg daily or every other day for 2‑3 weeks. Measure tumor volume and body weight twice weekly. At study end, harvest tumors for Western blot analysis of CARM1 levels and substrate methylation, qPCR for target gene expression, and immunohistochemistry for Ki‑67 and cleaved caspase‑3. Also analyze lung tissue for metastatic nodules (using bioluminescence imaging if using luciferase‑labeled cells).
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| ADME/Pharmacokinetics |
General pharmacokinetic protocol for CARM1 degrader-1 hydrochloride: Administer the compound to male Sprague‑Dawley rats via IV (1 mg/kg) and IP (10 mg/kg). Formulate in an appropriate vehicle (e.g., 10% DMSO, 50% PEG400, 40% saline). Collect blood samples at 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours. Analyze plasma concentrations by validated LC‑MS/MS method. Calculate PK parameters (Cmax, Tmax, AUC, t1/2, clearance, volume of distribution, IP bioavailability). PROTACs may exhibit moderate to low oral bioavailability; IV or IP routes are commonly used for in vivo studies.
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| Toxicity/Toxicokinetics |
General toxicity protocol for CARM1 degrader-1 hydrochloride: Perform a 14‑day repeated dose toxicity study in ICR mice. Administer the compound IP at doses of 5, 15, and 40 mg/kg daily. Monitor clinical signs, body weight, and food consumption daily. At termination, collect blood for hematology (CBC, differential) and serum chemistry (ALT, AST, ALP, BUN, creatinine). Perform gross necropsy and collect major organs for histopathological examination. Conduct proteomics analysis to assess potential off‑target degradation events, which is a concern for PROTAC molecules.
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| References | |
| Additional Infomation |
CARM1 degrader-1 hydrochloride (HY‑156152A) is a potent and selective CARM1 degrader that utilizes the VHL E3 ligase. CARM1 is an arginine methyltransferase that methylates various proteins involved in transcription, RNA processing, and signal transduction, and it is overexpressed in several cancers. The compound inhibits breast cancer cell migration by degrading CARM1 and reducing the methylation of its substrates. The hydrochloride salt form improves solubility and handling for research applications.
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| Molecular Formula |
C71H99CLN12O8S
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|---|---|
| Molecular Weight |
1316.14
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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, avoid exposure to moisture. |
| 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 : 6.67 mg/mL (5.07 mM; with sonication (<60°C))
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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 | 0.7598 mL | 3.7990 mL | 7.5980 mL | |
| 5 mM | 0.1520 mL | 0.7598 mL | 1.5196 mL | |
| 10 mM | 0.0760 mL | 0.3799 mL | 0.7598 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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