AT-007 is a novel and orally bioactive central nervous system (CNS) penetrant Aldose Reductase inhibitor for treatment of Galactosemia with an IC50 value of 100 pM. AT-007 reduces toxic galactitol levels and prevents disease complications in GALT deficiency rats.
Physicochemical Properties
| Molecular Formula | C17H10F3N3O3S2 |
| Molecular Weight | 425.404811382294 |
| Exact Mass | 425.011 |
| Elemental Analysis | C, 48.00 H, 2.37 F, 13.40 N, 9.88 O, 11.28 S, 15.07 |
| CAS # | 2170729-29-8 |
| PubChem CID | 132260161 |
| Appearance | White to off-white solid powder |
| LogP | 3.2 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 28 |
| Complexity | 690 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | ORQGHAJIWGGFJK-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C17H10F3N3O3S2/c18-17(19,20)8-1-2-13-12(3-8)21-14(28-13)5-23-16(26)10-7-27-6-9(10)11(22-23)4-15(24)25/h1-3,6-7H,4-5H2,(H,24,25) |
| Chemical Name | 2-(4-oxo-3-((5-(trifluoromethyl)benzo[d]thiazol-2-yl)methyl)-3,4-dihydrothieno[3,4-d]pyridazin-1-yl)acetic acid |
| Synonyms | AT-007 AT 007 AT007 |
| 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 Vivo | In GALT reserve organ tissues (liver, brain, and traction), AT-007 markedly decreased galactitol levels but did not raise galactose or Gal1P levels [2]. |
| References |
[1]. Maeve Conneighton, et al. Applied Therapeutics Announces Initiation of Phase 1/2 Study of AT-007 in Galactosemia. [2]. UNITED STATES SECURITIES AND EXCHANGE COMMISSION. APPLIED THERAPEUTICS, INC. |
| Additional Infomation | Gavorestat is under investigation in clinical trial NCT04902781 (Clinical Benefit, Safety, PK and PD Study of AT-007 in Pediatric Subjects With Classic Galactosemia). |
Solubility Data
| Solubility (In Vitro) | DMSO : ~35.71 mg/mL (~83.94 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (5.29 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 22.5 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. Solubility in Formulation 2: ≥ 2.25 mg/mL (5.29 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 22.5 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 | 2.3507 mL | 11.7536 mL | 23.5073 mL | |
| 5 mM | 0.4701 mL | 2.3507 mL | 4.7015 mL | |
| 10 mM | 0.2351 mL | 1.1754 mL | 2.3507 mL |