| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
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| Targets |
PRMT5 (protein arginine methyltransferase 5) when bound to MTA (methylthioadenosine), a metabolite that accumulates in MTAP-deleted cancer cells. The MTA-PRMT5 complex is selectively targeted by AMG 193, which inhibits PRMT5 activity preferentially in MTAP-deficient tumors. MTAP deletions occur in approximately 15% of all solid tumors.
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| ln Vitro |
AMG 193, when complexed with MTA, preferentially inhibits the growth of MTAP-deficient tumor cells by inhibiting PRMT5 with an IC50 of 0.107 uM, while protecting normal cells with wild-type MTAP. (R)-AMG-193 is the (R)-isomer of AMG 193 and serves as a tool for research into cancer biology and therapeutic strategies involving PRMT5 inhibition.
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| ln Vivo |
AMG 193, the parent compound, is an orally active MTA-cooperative PRMT5 inhibitor that suppresses tumor growth and induces tumor regression in mouse xenograft models. In human cell line and patient-derived xenograft models, AMG 193 synergizes with chemotherapies or the KRAS G12C inhibitor sotorasib, and combination treatment in vivo significantly inhibits tumor growth. Phase 1/2 clinical studies are ongoing.
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| Enzyme Assay |
Typical PRMT5 inhibition assay (methyltransferase activity): incubate recombinant PRMT5 (0.1-0.5 ug) with MTA (10-100 uM) and 50 mM Tris-HCl pH 8.5, 10 mM DTT, 0.01% Triton X-100, 1 uM [3H]-SAM, and 10 uM histone H4 peptide substrate (residues 1-21) in a total volume of 50 uL at 30degC for 1-2 hours. AMG 193 is added at varying concentrations (0.001-10 uM). The reaction is spotted onto P81 filter paper, washed, and counted. IC50 is calculated.
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| Cell Assay |
Cell viability protocol: culture MTAP-deleted cancer cell lines (e.g., HCT116 MTAP-null, NCI-H522) and MTAP wild-type normal cells in appropriate media. Treat with AMG 193 at concentrations ranging from 0.001-100 uM for 72-120 hours. Cell viability is measured by CellTiter-Glo assay. Symmetrical dimethylarginine (SDMA) levels (PRMT5 activity marker) are measured by Western blot using SDMA-specific antibody.
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| Animal Protocol |
Mouse xenograft models: establish subcutaneous xenografts of MTAP-deleted HCT116 cells (5×10⁶ cells/injection) in nude mice. When tumors reach ~150-200 mm3, administer AMG 193 orally at doses ranging from 10-100 mg/kg once daily for 21-28 days. Tumor volume is measured twice weekly. Tumors are harvested for SDMA and MTAP expression analysis by IHC. Combination studies with sotorasib or chemotherapies are performed similarly.
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| ADME/Pharmacokinetics |
No specific PK data is available for (R)-AMG-193. For the parent compound AMG 193, it is described as orally active with favorable oral bioavailability. Standard PK studies would involve IV/oral administration in rodents with plasma and tumor tissue collection, LC-MS/MS analysis to determine half-life, clearance, volume of distribution, and oral bioavailability.
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| Toxicity/Toxicokinetics |
In a Phase I first-in-human study of AMG 193 in patients with MTAP-deleted solid tumors, dose-limiting toxicities were reported in eight patients at doses ≥240 mg, including nausea, vomiting, fatigue, hypersensitivity reaction, and hypokalemia. The maximum tolerated dose was determined to be 1200 mg once daily. AMG 193 showed a favorable safety profile without clinically significant myelosuppression. Encouraging antitumor activity was observed across various MTAP-deleted solid tumors.
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| References |
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| Additional Infomation |
AMG 193 is a second-generation PRMT5 inhibitor designed to induce synthetic lethality in MTAP-null solid tumors while avoiding hematologic toxicity. (R)-AMG-193 is the (R)-isomer of AMG 193, supplied for research use with purity ≥98%. Molecular formula: C22H19F3N4O3, molecular weight: 444.41. Appearance: White to light yellow solid powder. Each product in one row, fields tab-separated.
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| Molecular Formula |
C22H19F3N4O3
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|---|---|
| Molecular Weight |
444.41
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| CAS # |
2790567-83-6
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| Related CAS # |
AMG-193;2790567-82-5
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| Appearance |
White to light 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) |
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 | 2.2502 mL | 11.2509 mL | 22.5017 mL | |
| 5 mM | 0.4500 mL | 2.2502 mL | 4.5003 mL | |
| 10 mM | 0.2250 mL | 1.1251 mL | 2.2502 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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