AG 636 (AG636; AG-636) is a novel,potent, reversible, selective and orally active dihydroorotate dehydrogenase (DHODH) inhibitor (IC50=17 nM) which has strong anticancer effects.
Physicochemical Properties
| Molecular Formula | C21H17N3O2 |
| Molecular Weight | 343.386 |
| Exact Mass | 343.132 |
| Elemental Analysis | C, 73.45; H, 4.99; N, 12.24; O, 9.32 |
| CAS # | 1623416-31-8 |
| PubChem CID | 77461001 |
| Appearance | White to off-white solid powder |
| Density | 1.27±0.1 g/cm3 |
| Boiling Point | 619.3±43.0 °C |
| LogP | 4.3 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 26 |
| Complexity | 506 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | OC(C1=CC(=CC2=C1N(C)N=N2)C1C=CC(=CC=1)C1C=CC=CC=1C)=O |
| InChi Key | GSBZRCGZLMBSNY-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H17N3O2/c1-13-5-3-4-6-17(13)15-9-7-14(8-10-15)16-11-18(21(25)26)20-19(12-16)22-23-24(20)2/h3-12H,1-2H3,(H,25,26) |
| Chemical Name | 1-methyl-5-(2'-methyl-[1,1'-biphenyl]-4-yl)-1H-benzo[d][1,2,3]triazole-7-carboxylic acid |
| Synonyms | AG 636 AG-636 AG636 |
| 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) |
Biological Activity
| ln Vitro | In tumor lines derived from solid and hematological tumors, AG-636 exhibits terminal growth inhibitory activity [1]. |
| ln Vivo | The OCILY19 DLBCL tumor xenograft model shows significant tumor growth inhibition in response to AG-636 (10–100 mg/kg; gavage; twice daily; for 14 days) [1]. |
| Animal Protocol |
Animal/Disease Models: Transgenic female 6-8 oneweeks old CB17/Icr-Prkdcscid/IcrIcoCrl (CB17 SCID) mice [1] injected with OCILY19 cells [1] Doses: 10 mg/kg, 30 mg/kg or 100 mg/kg Route of Administration: po (oral gavage); twice (two times) daily; for 14 days Experimental Results: Produced strong tumor growth inhibition in xenograft lymphoma model. |
| References |
[1]. Selective Vulnerability to Pyrimidine Starvation in Hematologic Malignancies Revealed by AG-636, a Novel Clinical-Stage Inhibitor of Dihydroorotate Dehydrogenase. Mol Cancer Ther. 2020 Dec;19(12):2502-2515. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~31.25 mg/mL (~91.01 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (6.06 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (6.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9121 mL | 14.5607 mL | 29.1214 mL | |
| 5 mM | 0.5824 mL | 2.9121 mL | 5.8243 mL | |
| 10 mM | 0.2912 mL | 1.4561 mL | 2.9121 mL |