| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
AM-9747 selectively targets PRMT5 in an MTA-cooperative manner, binding to the PRMT5-MTA complex that accumulates in MTAP-deleted cancer cells. It inhibits PRMT5-directed symmetric dimethylation of arginine residues (SDMA) of proteins, leading to reduction of cell viability in MTAP-deleted cells compared to MTAP-WT cells, with an IC50 of 2 nM for SDMA inhibition in HCT116 MTAP-deleted cells.
|
|---|---|
| ln Vitro |
With IC50 values of 0.026 and 0.068 μM, respectively, PRMT5-IN-25 (6 days) exhibits anti-proliferative effect on HCT116-MTAP null and HCT116-WT cells [1].
In vitro, AM-9747 inhibits PRMT5 with a Ki of 0.06 nM. It demonstrates potent antiproliferative activity against MTAP-deleted cancer cell lines (e.g., HCT116, DOHH-2, NCI-H2110) with IC50 values in the low nanomolar range. The compound shows >100-fold selectivity for MTAP-deleted over MTAP-WT cells, enabling a favorable therapeutic window. |
| ln Vivo |
In vivo, once-daily oral dosing of AM-9747 in mouse xenograft models is well tolerated, displaying robust and dose-dependent inhibition of symmetric dimethylation of arginine in MTAP-deleted tumor xenografts and significant concomitant tumor growth inhibition (TGI) without any significant effect on MTAP-WT tumor xenografts. Efficacy is observed in patient-derived xenograft (PDX) models.
|
| Enzyme Assay |
For non-cellular PRMT5 inhibition, purified PRMT5-MEP50 complex is incubated with a histone H4 peptide substrate and 3H-S-adenosylmethionine (SAM) in the presence of varying concentrations of AM-9747 (0.001-100 uM) and MTA (if required for cooperativity). The reaction is quenched, and the radiolabeled product is captured on filter papers for scintillation counting to determine Ki and IC50 values.
|
| Cell Assay |
For cell-based assays, MTAP-deleted cancer cell lines (e.g., HCT116 MTAP-del, DOHH-2) are seeded in 96-well plates and treated with AM-9747 (0.001-10 uM) for 72-96 hours. Cell viability is measured by CellTiter-Glo or MTT. Symmetric dimethylation of arginine (SDMA) levels are quantified by Western blotting using a specific antibody (e.g., SYM11). Cell cycle analysis is performed by flow cytometry using propidium iodide staining.
|
| Animal Protocol |
For in vivo evaluation, female athymic nude mice are subcutaneously implanted with MTAP-deleted tumor cells (e.g., HCT116 MTAP-del, DOHH-2). Once tumors reach ∼115 mm3, mice are orally dosed with AM-9747 at 100 mg/kg or vehicle once daily. Tumor volume is measured twice weekly. At study termination, tumors are harvested for SDMA Western blot analysis, immunohistochemistry (Ki-67, cleaved caspase-3), and histopathological examination.
|
| ADME/Pharmacokinetics |
AM-9747 is orally bioavailable with favorable pharmacokinetic properties supporting once-daily dosing. It exhibits moderate clearance and a terminal half-life compatible with oral administration. Detailed PK parameters (Cmax, AUC, t½) are described in the literature but not publicly summarized. The compound is well absorbed and distributed to tumor tissues.
|
| Toxicity/Toxicokinetics |
Comprehensive toxicology data for AM-9747 are not publicly available. As a PRMT5 inhibitor, on-target toxicities may include effects on normal MTAP-WT cells. However, AM-9747 is designed to be MTA-cooperative, providing selectivity for MTAP-deleted tumors. In preclinical studies, once-daily oral dosing in mouse xenografts is well tolerated without significant body weight loss or hematological toxicity.
|
| References | |
| Additional Infomation |
AM-9747 is a research-grade compound, not approved for human therapy. It was discovered through DNA-encoded library screening and is protected by patents. The MTA-cooperative mechanism enables selective targeting of PRMT5 in MTAP-deleted cancers, a common genetic alteration in multiple solid tumors. No clinical trials are registered for AM-9747.
|
| Molecular Formula |
C24H21F3N6O
|
|---|---|
| Molecular Weight |
466.458354711533
|
| Exact Mass |
466.172
|
| CAS # |
2691869-82-4
|
| PubChem CID |
156830143
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
3.2
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
34
|
| Complexity |
688
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
FC(C1=CN=C(C=C1)CN(C(C1C=CC2C(=CC(C)=C(N)N=2)C=1)=O)[C@@H](C1N=CC=CN=1)C)(F)F
|
| InChi Key |
QRZCNKOBDDQUAP-OAHLLOKOSA-N
|
| InChi Code |
InChI=1S/C24H21F3N6O/c1-14-10-17-11-16(4-7-20(17)32-21(14)28)23(34)33(15(2)22-29-8-3-9-30-22)13-19-6-5-18(12-31-19)24(25,26)27/h3-12,15H,13H2,1-2H3,(H2,28,32)/t15-/m1/s1
|
| Chemical Name |
2-amino-3-methyl-N-[(1R)-1-pyrimidin-2-ylethyl]-N-[[5-(trifluoromethyl)pyridin-2-yl]methyl]quinoline-6-carboxamide
|
| 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) |
DMSO : ~62.5 mg/mL (~133.99 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (13.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (13.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 6.25 mg/mL (13.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1438 mL | 10.7190 mL | 21.4381 mL | |
| 5 mM | 0.4288 mL | 2.1438 mL | 4.2876 mL | |
| 10 mM | 0.2144 mL | 1.0719 mL | 2.1438 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
