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| Targets |
PR5-LL-CM01 targets protein arginine methyltransferase 5 (PRMT5), an enzyme that catalyzes the symmetric dimethylation of arginine residues on histone and non-histone proteins. PRMT5 plays a critical role in epigenetic regulation, gene expression, and cell proliferation. It is overexpressed in various cancers and is associated with poor prognosis. By inhibiting PRMT5 with an IC₅₀ of 7.5 μM, PR5-LL-CM01 reduces arginine methylation, leading to changes in gene expression that inhibit cancer cell growth. The compound shows >10-fold selectivity over PRMT3. It also functions as an HDAC inhibitor, altering chromatin structure.
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| ln Vitro |
In PDAC cells (PANC1, MiaPaCa2, and AsPC1), the IC50 range of PR5-LL-CM01 is 2-4 μM, while in CRC cells (HT29, HCT116, and DLD1), it is 10-11 μM. CM01 shows minimal harm to healthy cells while having a high selectivity in suppressing cancer cells. PANC1 and HT29 cells' capacity to form colonies is significantly inhibited by PR5-LL-CM01 [1]. In PDAC and CRC cells, PR5-LL-CM01 suppresses NF-κB activity and the expression of its target gene [1]. In PANC1 and HT29 cells, PR5-LL-CM01 (0–15 μM) dramatically lowers the levels of TNFα and IL8 [1].
In vitro, PR5-LL-CM01 inhibits PRMT5 with an IC₅₀ of 7.5 μM and displays >10-fold selectivity over PRMT3. It shows significant anti-proliferative activity in various solid tumor models. The compound is a novel PRMT5 inhibitor with anti-tumor activities in pancreatic and colorectal cancers. Detailed cellular activity data, such as effects on PRMT5 substrate methylation and cell proliferation, are consistent with its mechanism of action. |
| ln Vivo |
Significant anti-tumor effects are demonstrated by PR5-LL-CM01 (20 mg/kg; intraperitoneal injection; three times a week) [1].
Detailed in vivo activity data for PR5-LL-CM01 are not extensively reported in the available literature. As a potent PRMT5 inhibitor with anti-tumor activities, it is expected to have in vivo efficacy in tumor models. However, specific in vivo efficacy data from animal studies are not provided in the available sources. Further studies are needed to confirm its therapeutic potential. |
| Enzyme Assay |
Non-cell-based enzyme assays for PR5-LL-CM01 typically involve in vitro methyltransferase activity assays using purified recombinant PRMT5 enzyme. The compound is incubated with the enzyme, a peptide substrate, and the methyl donor S-adenosylmethionine (SAM) at varying concentrations. Methyltransferase activity is measured by quantifying the transfer of methyl groups to the substrate using radiometric (³H-SAM), fluorescence-based, or mass spectrometry methods. IC₅₀ values for enzyme inhibition are determined from dose-response curves. Selectivity profiling against PRMT3 and other methyltransferases is performed.
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| Cell Assay |
Cellular assays for PR5-LL-CM01 are performed using pancreatic and colorectal cancer cell lines. Cells are treated with the compound at various concentrations for specified durations. PRMT5 substrate methylation (e.g., symmetric dimethylarginine, SDMA) is measured by Western blotting using specific antibodies. Cell proliferation is assessed using standard viability assays. Apoptosis is evaluated using Annexin V/PI staining or caspase activity assays. Histone acetylation levels are measured to confirm HDAC inhibition.
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| Animal Protocol |
Animal/Disease Models: 6-8 weeks old male NSG mice (carrying PANC1 or HT29 cells) [1]
Doses: 20 mg/kg (API dissolved in 1:1 Cremophor:ethanol solution) Route of Administration: weekly intraperitoneal (ip) injection 3 times; 32 days (PANC1 model); 10 days (HT29 model). Experimental Results: Significant tumor inhibition was produced in both PANC1 and HT29 xenograft mice. There was no significant effect on mouse body weight. In vivo animal models for PR5-LL-CM01 would be required to assess its therapeutic potential. Based on its mechanism as a PRMT5 inhibitor with anti-tumor activities in pancreatic and colorectal cancers, relevant models could include xenograft studies in immunodeficient mice bearing pancreatic or colorectal cancer cell lines. The compound would be administered via appropriate routes at various doses. Tumor growth inhibition would be monitored over time. Pharmacodynamic markers such as SDMA levels and histone acetylation in tumor tissues would be assessed. |
| ADME/Pharmacokinetics |
PR5-LL-CM01 has a molecular weight of 401.51 g/mol and a molecular formula of C₂₃H₂₇N₇. CAS number is 1005307-86-7. The compound is a solid. Purity is not specified but is of research grade. Storage conditions: powder at -20°C; in solvent at -80°C. Detailed PK parameters such as half-life and bioavailability are not extensively reported. The compound is supplied for research use only.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for PR5-LL-CM01 are not extensively reported in the available literature. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is supplied for research use only and is not for human consumption. Given its mechanism of PRMT5 and HDAC inhibition, potential effects on epigenetic regulation in normal tissues would be key safety considerations.
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| References | |
| Additional Infomation |
PR5-LL-CM01 is a potent protein arginine methyltransferase 5 (PRMT5) inhibitor with an IC₅₀ of 7.5 μM. It displays >10-fold selectivity over PRMT3. The compound is a novel PRMT5 inhibitor with anti-tumor activities in pancreatic and colorectal cancers. It also functions as an HDAC inhibitor, altering chromatin structure and activating tumor suppressor gene transcription. PR5-LL-CM01 shows significant anti-proliferative activity in various solid tumor models. It is for research use only.
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| Molecular Formula |
C23H27N7
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| Molecular Weight |
401.507383584976
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| Exact Mass |
401.232
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| CAS # |
1005307-86-7
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| PubChem CID |
18567017
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| Appearance |
White to off-white solid powder
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
524
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(C2C=CC=CC=2)C2C(C=N1)=C(N=C(N=2)NCCN(C)C)NC1=CC=C(C)C(C)=C1
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| InChi Key |
UPAZOMJFUXPAJI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H27N7/c1-16-10-11-18(14-17(16)2)26-21-20-15-25-30(19-8-6-5-7-9-19)22(20)28-23(27-21)24-12-13-29(3)4/h5-11,14-15H,12-13H2,1-4H3,(H2,24,26,27,28)
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| Chemical Name |
6-N-[2-(dimethylamino)ethyl]-4-N-(3,4-dimethylphenyl)-1-phenylpyrazolo[3,4-d]pyrimidine-4,6-diamine
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| Synonyms |
PR5-LL-CM01PR5-LLCM01PR5LL-CM01
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~11.11 mg/mL (~27.67 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 | 2.4906 mL | 12.4530 mL | 24.9060 mL | |
| 5 mM | 0.4981 mL | 2.4906 mL | 4.9812 mL | |
| 10 mM | 0.2491 mL | 1.2453 mL | 2.4906 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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