| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Type I protein arginine methyltransferases (PRMT1, PRMT3, PRMT4, PRMT6, PRMT8) with Ki values ranging from 1.5 to 81 nM [1]
|
|---|---|
| ln Vitro |
- GSK3368715 is a potent, reversible, and S-adenosylmethionine (SAM)-uncompetitive inhibitor of type I PRMTs. It alters the arginine methylation status of hundreds of substrates, shifting from asymmetric dimethylarginine (ADMA) to monomethylarginine (MMA) and symmetric dimethylarginine (SDMA) [1]
- As a monotherapy, GSK3368715 exhibits antiproliferative effects on various hematological and solid tumor cell lines in vitro. In Cell Western assays, RKO cells seeded in clear-bottom 384-well plates were treated with a 20-point two-fold dilution series of GSK3368715 (29,325.5 to 0.03 nM) or 0.15% DMSO, followed by incubation at 37°C in 5% CO₂ for 3 days. Results showed strong antiproliferative activity [1] - GSK3368715 synergizes with PRMT5 inhibitors (e.g., GSK3326595) to enhance antiproliferative effects in MTAP-deficient cancer cell lines, as indicated by reduced cell viability compared to single-agent treatments [1] |
| ln Vivo |
- GSK3368715 completely inhibits tumor growth or induces tumor regression in in vivo tumor models. In MTAP-deficient xenograft models, administration of GSK3368715 results in significant tumor growth inhibition, with greater efficacy observed in MTAP-deficient tumors compared to MTAP-proficient counterparts [1]
- Combination of GSK3368715 with a PRMT5 inhibitor (GSK3326595) shows enhanced antitumor activity in MTAP-deficient xenografts, leading to more pronounced tumor regression than either agent alone [1] |
| Cell Assay |
- Antiproliferation assay: RKO cells were seeded in clear-bottom 384-well plates and treated with serial concentrations of GSK3368715 or 0.15% DMSO (control). After incubation at 37°C in 5% CO₂ for 3 days, cells were fixed with ice-cold methanol for 30 minutes at room temperature, washed with PBS, and incubated with blocking buffer for 1 hour at room temperature. Cell viability and proliferation were assessed using appropriate detection methods [1]
- Synergy assay: MTAP-deficient and MTAP-proficient cancer cells were treated with GSK3368715 alone, PRMT5 inhibitor alone, or their combination. Cell viability was measured after 72 hours, and combination index (CI) was calculated to determine synergism [1] |
| Animal Protocol |
Xenograft models: Nude mice bearing MTAP-deficient or MTAP-proficient tumor xenografts were administered GSK3368715 via oral gavage at specified doses. For combination studies, mice received GSK3368715 and PRMT5 inhibitor (GSK3326595) according to a predefined schedule. Tumor volume was measured regularly, and mice were monitored for survival and body weight changes [1]
|
| References | |
| Additional Infomation |
Type I PRMTs catalyze the asymmetric dimethylation of arginine residues, and their dysregulation is associated with human cancers. GSK3368715 targets these enzymes to interfere with oncogenic signaling pathways [1] - MTAP deficiency leads to the accumulation of 2-methylthioadenosine (MTA, an endogenous PRMT5 inhibitor), making MTAP-deficient cancers more sensitive to GSK3368715 and enhancing its synergistic effect with PRMT5 inhibitors [1]
|
| Molecular Formula |
C20H39CLN4O2
|
|---|---|
| Molecular Weight |
403.00
|
| CAS # |
2227587-25-7
|
| Related CAS # |
GSK3368715;1629013-22-4;GSK3368715 dihydrochloride;1628925-77-8;GSK3368715 trihydrochloride;2227587-26-8
|
| Appearance |
Typically exists as solids at room temperature
|
| SMILES |
Cl.O(CC)CC1(COCC)CCC(C2=C(C=NN2)CN(C)CCNC)CC1
|
| Synonyms |
EPZ019997 hydrochloride; GSK-3368715 (hydrochloride); 2227587-25-7; N1-((3-(4,4-Bis(ethoxymethyl)cyclohexyl)-1H-pyrazol-4-yl)methyl)-N1,N2-dimethylethane-1,2-diamine hydrochloride; N'-[[5-[4,4-bis(ethoxymethyl)cyclohexyl]-1H-pyrazol-4-yl]methyl]-N,N'-dimethylethane-1,2-diamine;hydrochloride; GSK715 hydrochloride; EPZ019997 hydrochloride; GSK3368715 hydrochloride; orb2283276;
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 2.4814 mL | 12.4069 mL | 24.8139 mL | |
| 5 mM | 0.4963 mL | 2.4814 mL | 4.9628 mL | |
| 10 mM | 0.2481 mL | 1.2407 mL | 2.4814 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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