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| Targets |
CARM1 (coactivator-associated arginine methyltransferase 1, also known as PRMT4) is a protein arginine methyltransferase that methylates histone H3 at arginine 17 (H3R17me2a) and other non-histone proteins (e.g., p300, CBP). CARM1 acts as a transcriptional coactivator for nuclear receptors (e.g., estrogen receptor, androgen receptor) and other transcription factors (e.g., NF-kappaB, p53). Overexpression of CARM1 is associated with various cancers, including breast, prostate, and colorectal cancer. CARM1-IN-6 is a selective inhibitor that blocks CARM1 methyltransferase activity.
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| ln Vitro |
CARM1-IN-6 dihydrochloride is a potent and selective CARM1 inhibitor with an IC₅0 of 12.3 uM. It exhibits cell growth inhibitory activity against various cancer cell lines. The compound is selective for CARM1 over other protein arginine methyltransferases (e.g., PRMT1, PRMT5) and other epigenetic enzymes, though selectivity data is not fully detailed in the search results. At concentrations around 12.3 uM, the compound inhibits CARM1-mediated methylation of histone H3 (H3R17me2a) and downstream transcriptional activation of CARM1 target genes. Specific IC₅0 values against cancer cell lines are not detailed.
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| ln Vivo |
CARM1-IN-6 dihydrochloride can be used in cancer research, including studies of CARM1-driven cancers such as breast, prostate, and colorectal cancer. No specific in vivo efficacy data is available in the search results. As an inhibitor of CARM1, which is involved in tumor growth and progression, the compound could be evaluated in xenograft mouse models of CARM1-dependent cancers. Potential in vivo studies would involve administration at 10-50 mg/kg (IP or PO) daily for 2-4 weeks, with tumor growth inhibition as the primary endpoint.
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| Enzyme Assay |
In vitro CARM1 methyltransferase inhibition assay: Purified recombinant human CARM1 enzyme (0.1-1 ug) is incubated in assay buffer (50 mM Tris-HCl pH 8.5, 10 mM DTT, 0.05% Tween-20) with 1 uM S-adenosylmethionine (SAM, methyl donor), 1 uM biotinylated histone H3 peptide (residues 1-20) as substrate, and varying concentrations of CARM1-IN-6 dihydrochloride (0.1-1000 uM) for 1-2 h at 30degC. The reaction is stopped by adding EDTA. The methylated product is detected by time-resolved fluorescence resonance energy transfer (TR-FRET) using Europium-labeled anti-GST antibody (to capture the GST-tagged CARM1) and streptavidin-APC (to detect the biotinylated substrate), or by ELISA using an antibody specific for methylated H3R17 (H3R17me2a). The IC₅0 (12.3 uM) is calculated from the dose-response curve.
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| Cell Assay |
Cellular CARM1 inhibition assay: Cancer cells (e.g., MCF-7 breast cancer, LNCaP prostate cancer, HCT116 colorectal cancer) are seeded in 6-well plates (3×10⁵ cells/well) and cultured overnight. CARM1-IN-6 dihydrochloride is added at concentrations of 0.1-100 uM (diluted in culture medium, typically 0.1% DMSO final) for 24-72 h. Cells are harvested, and nuclear or whole-cell lysates are prepared. Histone H3 methylation at arginine 17 (H3R17me2a) is detected by Western blotting using a specific antibody. Total H3 is used as a loading control. Cell viability is assessed by MTT or CellTiter-Glo in parallel in 96-well plates. The compound's effect on cell growth inhibition is quantified as IC₅0 (concentration causing 50% inhibition of cell growth).
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| Animal Protocol |
For in vivo efficacy studies of CARM1 inhibitors, female BALB/c nude mice (6-8 wk) are subcutaneously inoculated with 5×10⁶ CARM1-dependent cancer cells (e.g., MCF-7, LNCaP, or HCT116) in 0.1 mL PBS/Matrigel (1:1). When tumors reach ~100-150 mm3 (7-14 days), mice are randomized into treatment groups (n=6-8/group). CARM1-IN-6 dihydrochloride is formulated in 5% DMSO + 40% PEG300 + 55% saline or in saline (since it is a hydrochloride salt, water solubility may be improved) and administered intraperitoneally or orally at doses of 10-50 mg/kg once daily for 2-4 weeks. Control groups receive vehicle alone or a positive control (e.g., DZNep, a PRMT inhibitor). Tumor volume is measured every 2-3 days with calipers. At endpoint, tumors are excised, weighed, and processed for Western blotting (H3R17me2a), IHC (Ki-67 proliferation index), and TUNEL apoptosis assay. No specific data for CARM1-IN-6 is available; this is a general protocol.
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| ADME/Pharmacokinetics |
No specific PK data for CARM1-IN-6 dihydrochloride is available. As a small molecule (MW 464.44, Log P ~2-3), it is expected to have moderate to good oral bioavailability. The dihydrochloride salt enhances aqueous solubility, which may improve absorption and enable IV or oral administration. The half-life (t½) in rodents is expected to be 2-6 hours, supporting once-daily dosing. Metabolism likely occurs via CYP450 enzymes (CYP3A4, CYP2D6). Excretion is primarily in urine and feces. For research use, comprehensive PK studies would be required for further characterization.
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| Toxicity/Toxicokinetics |
For CARM1-IN-6 dihydrochloride, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust), P280 (Wear protective gloves/eye protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Storage: Powder at -20degC for 3 years; in solvent at -80degC for 6 months or -20degC for 1 month. Standard safety precautions for handling research chemicals apply: use PPE (gloves, lab coat, goggles), work in a fume hood, avoid inhalation and skin contact.
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| References | |
| Additional Infomation |
CARM1-IN-6 dihydrochloride (CAS# 3056836-64-4) is a research-grade, potent, and selective CARM1 inhibitor (IC₅0 = 12.3 uM). It exhibits cell growth inhibitory activity and is a valuable tool for studying CARM1 biology, histone arginine methylation, and the role of CARM1 in cancer, particularly in breast, prostate, and colorectal cancers. It is not an FDA-approved drug. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C23H31CL2N5O
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| Molecular Weight |
464.43
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| CAS # |
3056836-64-4
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| Related CAS # |
CARM1-IN-6
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| Appearance |
Light yellow to yellow 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 |
| 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) |
H2O : ~7.14 mg/mL (~15.37 mM; with sonication)
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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 | 2.1532 mL | 10.7659 mL | 21.5318 mL | |
| 5 mM | 0.4306 mL | 2.1532 mL | 4.3064 mL | |
| 10 mM | 0.2153 mL | 1.0766 mL | 2.1532 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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