Tolimidone

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

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

1. Saporito MS, Lipinski CA, Reaume AG (2012). "Chapter 9:Phenotypic In Vivo Screening to Identify New, Unpredicted Indications for Existing Drugs and Drug Candidates". In Barratt MJ, Frail DE (eds.). Drug Repositioning: Bringing New Life to Shelved Assets and Existing Drugs. John Wiley & Sons. p. 270. ISBN   978-1-118-27439-2.
2. "Tolimidone". AdisInsight. Springer Nature Switzerland AG. Retrieved 26 August 2017.
3. 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
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". Bioorganic & Medicinal Chemistry. 28 (9) 115425. doi: 10.1016/j.bmc.2020.115425 . PMID   32201192.
5. 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.^{[ permanent dead link ]}
6. 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.
7. "Melior Pharmaceuticals Announces Positive Results in Phase 2B Study with Tolimidone for Type 2 Diabetes" (Press release). 14 May 2019.
8. "Melior Pharmaceuticals Announces Positive Phase 2A Results in Type 2 Diabetes Study". www.businesswire.com. June 13, 2016.
9. Lee MK, Kim SG, Watkins E, Moon MK, Rhee SY, Frias JP, et al. (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) 107555. doi:10.1016/j.jdiacomp.2020.107555. PMID   32019723. S2CID   211036334.