| Iupac name | 5-(3-methylphenoxy)pyrimidin-2(1H)-one |
|---|---|
| Cas number | 41964-07-2 |
| Pubchem | 39065 |
| Chemspiderid | 35751 |
| Chembl | 8030 |
| Unii | MU3JD8E9IS |
| Kegg | D06182 |
| Synonyms | CP-26154, MLR-1023 |
| C | 11 |
| H | 10 |
| N | 2 |
| O | 2 |
| Smiles | O=C2/N=C\C(\Oc1cc(ccc1)C)=C/N2 |
Tolimidone (CP-26154; MLR-1023) is a compound which was discovered by scientists at Pfizer, was found to stimulate secretion of gastric mucosa, and was in development by Pfizer as a drug candidate to treat gastric ulcers but was abandoned.[1][2][3][4] After the patent on the compound expired, scientists at the company Melior Discovery identified it as a potential drug candidate for diabetes through a phenotypic screen.[4] The company proceeded to show that MLR-1023 is an allosteric activator of Lyn kinase with an EC50 of 63 nM.[5][6] As of 2012 Melior was repurposing it for diabetes.[1][7] In June 2016, the company reported positive results from their Phase 2a clinical study in diabetic subjects[8][9]
References
- ^ Saporito MS, Lipinski CA, Reaume AG (2012). "Chapter 9:Phenotypic In Vivo Screening to Identify New, Unpredicted Indications for Existing Drugs and Drug Candidates". Drug Repositioning: Bringing New Life to Shelved Assets and Existing Drugs. John Wiley & Sons. p. 270. ISBN 978-1-118-27439-2.
- ^ "Tolimidone". AdisInsight. Springer Nature Switzerland AG. Retrieved 26 August 2017.
- ^ Lipinski CA, Stam JG, Pereira JN, Ackerman NR, Hess HJ (September 1980). "Bronchodilator and antiulcer phenoxypyrimidinones". Journal of Medicinal Chemistry. 23 (9): 1026–1031. doi:10.1021/jm00183a012. PMID 7411545
Compound 3 has been assigned the nonproprietary (USAN) name tolimidone
- ^ Lipinski CA, Reaume AG (May 2020). "High throughput in vivo phenotypic screening for drug repurposing: Discovery of MLR-1023 a novel insulin sensitizer and novel Lyn kinase activator with clinical proof of concept". Bioorganic & Medicinal Chemistry. 28 (9). doi:10.1016/j.bmc.2020.115425. PMID 32201192
- ^ Ochman AR, Lipinski CA, Handler JA, Reaume AG, Saporito MS (July 2012). "The Lyn kinase activator MLR-1023 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes". The Journal of Pharmacology and Experimental Therapeutics. 342 (1): 23–32. doi:10.1124/jpet.112.192187. PMID 22431203. S2CID 7288053[dead link]
- ^ Saporito MS, Ochman AR, Lipinski CA, Handler JA, Reaume AG (July 2012). "MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo". The Journal of Pharmacology and Experimental Therapeutics. 342 (1): 15–22. doi:10.1124/jpet.112.192096. PMID 22473614. S2CID 26419896
- ^ "Melior Pharmaceuticals Announces Positive Results in Phase 2B Study with Tolimidone for Type 2 Diabetes". 14 May 2019.
- ^ "Melior Pharmaceuticals Announces Positive Phase 2A Results in Type 2 Diabetes Study". www.businesswire.com. June 13, 2016.
- ^ Lee MK, Kim SG, Watkins E, Moon MK, Rhee SY, Frias JP, Chung CH, Lee SH, Block B, Cha BS, Park HK, Kim BJ, Greenway F (May 2020). "A novel non-PPARgamma insulin sensitizer: MLR-1023 clinicalproof-of-concept in type 2 diabetes mellitus". Journal of Diabetes and Its Complications. 34 (5). doi:10.1016/j.jdiacomp.2020.107555. PMID 32019723. S2CID 211036334