Pyrazolyl-pyrimidones inhibit the function of human solute carrier protein SLC11A2 (hDMT1) by metal chelation
Year: 2020
Type: article
Abstract: = 1.1 μM) pyrazolyl-pyrimidone inhibitor of radiolabeled iron uptake in hDMT1 overexpressing HEK293 cells acting by a non-competitive mechanism, which however does not affect the electrophysiological properties of the transporter. Isothermal titration calorimetry, competition with calcein, induced precipitation of radioactive iron and cross inhibition of the unrelated iron transporter SLC39A8 (hZIP8) indicate that inhibition is mediated by metal chelation. Mapping the chemical space of thousands of pyrazolo-pyrimidones and similar 2,2'-diazabiaryls in ChEMBL suggests that their reported activities might partly reflect metal chelation. Such metal chelating groups are not listed in pan-assay interference compounds (PAINS) but should be checked when addressing SLCs.
Source: RSC Medicinal Chemistry
DOI: 10.1039/d0md00085j
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: Purchase of a single crystal X-ray diffractometer for high resolution and accurate studies on molecular crystals, G298171496, G3188738659, Intestinal absorption of transition metals in human health and disease, NCCR TransCure - From transport physiology to identification of therapeutic targets
OpenAlex ID: W3033094483