Tolimidone

{{short description|Chemical compound}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Drugbox

| verifiedrevid =

| IUPAC_name = 5-(3-methylphenoxy)pyrimidin-2(1H)-one

| image = Tolimidone.svg

| tradename =

| pregnancy_category =

| legal_status =

| routes_of_administration =

| bioavailability =

| metabolism =

| excretion =

| CAS_number = 41964-07-2

| ATC_suffix =

| PubChem = 39065

| DrugBank =

| ChemSpiderID = 35751

| ChEMBL = 8030

| UNII_Ref = {{fdacite|correct|FDA}}

| 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.{{cite web|title=Tolimidone|url=http://adisinsight.springer.com/drugs/800023467|publisher=Springer Nature Switzerland AG | work = AdisInsight|access-date=26 August 2017|language=en}}{{cite journal | vauthors = Lipinski CA, Stam JG, Pereira JN, Ackerman NR, Hess HJ | title = Bronchodilator and antiulcer phenoxypyrimidinones | journal = Journal of Medicinal Chemistry | volume = 23 | issue = 9 | pages = 1026–1031 | date = September 1980 | pmid = 7411545 | doi = 10.1021/jm00183a012 | quote = Compound 3 has been assigned the nonproprietary (USAN) name tolimidone }}{{cite journal | vauthors = Lipinski CA, Reaume AG | title = 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 | journal = Bioorganic & Medicinal Chemistry | volume = 28 | issue = 9 | pages = 115425 | date = May 2020 | pmid = 32201192 | doi = 10.1016/j.bmc.2020.115425 | doi-access = free }} 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. The company proceeded to show that MLR-1023 is an allosteric activator of Lyn kinase with an EC50 of 63 nM.{{cite journal | vauthors = Ochman AR, Lipinski CA, Handler JA, Reaume AG, Saporito MS | title = 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 | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 342 | issue = 1 | pages = 23–32 | date = July 2012 | pmid = 22431203 | doi = 10.1124/jpet.112.192187 | s2cid = 7288053 }}{{Dead link|date=October 2023 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Saporito MS, Ochman AR, Lipinski CA, Handler JA, Reaume AG | title = MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 342 | issue = 1 | pages = 15–22 | date = July 2012 | pmid = 22473614 | doi = 10.1124/jpet.112.192096 | s2cid = 26419896 }} As of 2012 Melior was repurposing it for diabetes.{{cite book| vauthors = Saporito MS, Lipinski CA, Reaume AG | veditors = Barratt MJ, Frail DE |title=Drug Repositioning: Bringing New Life to Shelved Assets and Existing Drugs|date=2012|publisher=John Wiley & Sons|isbn=978-1-118-27439-2|page=270|chapter-url=https://books.google.com/books?id=TqOBrx_xZgAC&pg=PA270|language=en|chapter=Chapter 9:Phenotypic In Vivo Screening to Identify New, Unpredicted Indications for Existing Drugs and Drug Candidates}}{{Cite press release|url=https://www.businesswire.com/news/home/20190514005095/en/Melior-Pharmaceuticals-Announces-Positive-Results-Phase-2B | title = Melior Pharmaceuticals Announces Positive Results in Phase 2B Study with Tolimidone for Type 2 Diabetes| date = 14 May 2019}} In June 2016, the company reported positive results from their Phase 2a clinical study in diabetic subjects{{Cite web|url=https://www.businesswire.com/news/home/20160613005028/en/Melior-Pharmaceuticals-Announces-Positive-Phase-2A-Results-in-Type-2-Diabetes-Study|title=Melior Pharmaceuticals Announces Positive Phase 2A Results in Type 2 Diabetes Study|date=June 13, 2016|website=www.businesswire.com}}{{cite journal | vauthors = 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 | title = A novel non-PPARgamma insulin sensitizer: MLR-1023 clinicalproof-of-concept in type 2 diabetes mellitus | journal = Journal of Diabetes and Its Complications | volume = 34 | issue = 5 | pages = 107555 | date = May 2020 | pmid = 32019723 | doi = 10.1016/j.jdiacomp.2020.107555 | s2cid = 211036334 }}