Identification of Triazolothiadiazoles as Potent Inhibitors of the dCTP Pyrophosphatase 1
2017 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 60, no 5, 2148-2154 p.Article in journal (Refereed) Published
The dCTP pyrophosphatase 1 (dCTPase) is involved in the regulation of the cellular dNTP pool and has been linked to cancer progression. Here we report on the discovery of a series of 3,6-disubstituted triazolothiadiazoles as potent dCTPase inhibitors. Compounds 16 and 18 display good correlation between enzymatic inhibition and target engagement, together with efficacy in a cellular synergy model, deeming them as a promising starting point for hit -to-lead development.
Place, publisher, year, edition, pages
AMER CHEMICAL SOC , 2017. Vol. 60, no 5, 2148-2154 p.
IdentifiersURN: urn:nbn:se:uu:diva-319535DOI: 10.1021/acsjmedchem.6b01786ISI: 000396296100037PubMedID: 28145708OAI: oai:DiVA.org:uu-319535DiVA: diva2:1087255
FunderKnut and Alice Wallenberg FoundationSwedish Research CouncilEU, European Research CouncilGöran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of TechnologySwedish Cancer SocietySwedish Childhood Cancer FoundationTorsten Söderbergs stiftelseRagnar Söderbergs stiftelse