Tolimidone

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.[5] The company proceeded to show that MLR-1023 is an allosteric activator of Lyn kinase with an EC50 of 63 nM.[6][7] As of 2012 Melior was repurposing it for diabetes.[1][8] In June 2016, the company reported positive results from their Phase 2a clinical study in diabetic subjects[9][10]

Tolimidone

Clinical data
Other names	CP-26154, MLR-1023
Identifiers
IUPAC name 5-(3-methylphenoxy)pyrimidin-2(1H)-one
CAS Number	41964-07-2
PubChem CID	39065
ChemSpider	35751
UNII	MU3JD8E9IS
KEGG	D06182
ChEMBL	ChEMBL8030
CompTox Dashboard (EPA)	DTXSID50194786
ECHA InfoCard	100.230.742
Chemical and physical data
Formula	C11H10N2O2
Molar mass	202.213 g·mol^−1
3D model (JSmol)	Interactive image
SMILES O=C2/N=C\C(\Oc1cc(ccc1)C)=C/N2

References

1. Saporito, Michael S.; Lipinski, Christopher A.; Reaume, Andrew G. (2012). "Chapter 9:Phenotypic In Vivo Screening to Identify New, Unpredicted Indications for Existing Drugs and Drug Candidates". In Barratt, Michael J.; Frail, Donald E. (eds.). Drug Repositioning: Bringing New Life to Shelved Assets and Existing Drugs. John Wiley & Sons. p. 270. ISBN 9781118274392.
2. "Tolimidone". AdisInsight. Retrieved 26 August 2017.
3. Lipinski, C. A.; Stam, J. G.; Pereira, J. N.; Ackerman, N. R.; Hess, H. J. (1980). "Bronchodilator and antiulcer phenoxypyrimidinones". Journal of Medicinal Chemistry. 23 (9): 1026–31. doi:10.1021/jm00183a012. PMID 7411545. Compound 3 has been assigned the nonproprietary (USAN) name tolimidone
4. 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". Bioorg Med Chem. 28 (8): 115425. doi:10.1016/j.bmc.2020.115425.
5. 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". Bioorg Med Chem. 28 (8): 115425. doi:10.1016/j.bmc.2020.115425.
6. Ochman AR, Lipinski CA, Handler JA, Reaume AG, Saporito MS (2012). "The Lyn kinase activator MLR-123 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes". J Pharmacol Exp Therap. 342 (1): 23–32. doi:10.1124/jpet.112.192187.
7. Saporito MS, Ochman AR, Lipinski CA, Handler JA, Reaume AG (2011). "MLR-1023 is potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo". JPharmacol Exp Therap. 342 (1): 15–22. doi:10.1124/jpet.112.192096.
8. "Melior Discovery website press releases".
9. "Melior Pharmaceuticals Announces Positive Phase 2A Results in Type 2 Diabetes Study".
10. 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 Clinical Proof-of-concept in Type 2 Diabetes Mellitus". J. Diabetes Complications. 34 (5): 107555. doi:10.1016/j.jdiacomp.2020.107555. PMID 32019723.