Ponalrestat (MK-538; ICI 128436; Statil) is a novel and potent aldose reductase inhibitor which inhibits the conversion of glucose to sorbitol. Ponalrestat inhibits cachexia syndrome induced by colon26 adenocarcinoma in mice. Ponalrestat activates lipoprotein lipase (LPL) activity in the adipose tissue and alleviates the cachectic symptoms induced by B16 melanoma in mice. Ponalrestat is effective in the attenuation of the cachectic symptoms induced by human melanomas G361 and SEKI in nude mice, suggesting that ponalrestat has a potential usefulness for the treatment of cancer cachexia.
Physicochemical Properties
| Molecular Formula | C17H11N2O3FBR- |
| Molecular Weight | 390.18324 |
| Exact Mass | 390.001 |
| CAS # | 72702-95-5 |
| PubChem CID | 5278 |
| Appearance | White to off-white solid powder |
| Density | 1.6±0.1 g/cm3 |
| Boiling Point | 576.3±60.0 °C at 760 mmHg |
| Melting Point | 184-186ºC (DEC.) |
| Flash Point | 302.4±32.9 °C |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C |
| Index of Refraction | 1.663 |
| LogP | 2.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 24 |
| Complexity | 542 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | LKBFFDOJUKLQNY-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C17H12BrFN2O3/c18-11-6-5-10(14(19)7-11)9-21-17(24)13-4-2-1-3-12(13)15(20-21)8-16(22)23/h1-7H,8-9H2,(H,22,23) |
| Chemical Name | 2-(3-(4-bromo-2-fluorobenzyl)-4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid |
| Synonyms | Ponalrestat, ICI-128436; ICI 128436; ICI128436; MK-538; MK 538; MK538. trade name: Statil; Statyl. |
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 cultured endometrium and endometrial explants, Ponalrestat (ICI 128436; 1, 10, 100 μM; 6 hours) decreases PGF2α production in response to IL-1 [2]. |
| ln Vivo | Pomalrestat (ICI 128436; 10, 50 mg/kg; sidewall; daily; 8 weeks) effectively inhibits aldose reductase and decreases the accumulation of sorbitol [3]. |
| Animal Protocol |
Animal/Disease Models: Adult female SD (SD (Sprague-Dawley)) rats [3] Doses: 10, 50 mg/kg Route of Administration: oral; daily; 8-week Experimental Results: sorbitol accumulation diminished. |
| References |
[1]. Ponalrestat: a potent and specific inhibitor of aldose reductase. Biochem Pharmacol. 1990 Jan 15;39(2):337-46. [2]. The human aldose reductase AKR1B1 qualifies as the primary prostaglandin F synthase in the endometrium. J Clin Endocrinol Metab. 2011 Jan;96(1):210-9. [3]. Prevention of sensory disorders in diabetic Sprague-Dawley rats by aldose reductase inhibition or treatment with ciliary neurotrophic factor. Diabetologia. 2004 Apr;47(4):718-24. |
| Additional Infomation | 2-[3-[(4-bromo-2-fluorophenyl)methyl]-4-oxo-1-phthalazinyl]acetic acid is a member of phthalazines. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~62.5 mg/mL (~159.77 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.32 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 | 2.5629 mL | 12.8146 mL | 25.6292 mL | |
| 5 mM | 0.5126 mL | 2.5629 mL | 5.1258 mL | |
| 10 mM | 0.2563 mL | 1.2815 mL | 2.5629 mL |