Miller, Siennah R’s team published research in Drug Metabolism & Disposition in 2020-07-31 | 112-63-0

Drug Metabolism & Disposition published new progress about Equilibrative nucleoside transporters, ENT1/SLC29A1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate.

Miller, Siennah R.; Hau, Raymond K.; Jilek, Joseph L.; Morales, Mark N.; Wright, Stephen H.; Cherrington, Nathan J. published the artcile< Nucleoside reverse transcriptase inhibitor interaction with human equilibrative nucleoside transporters 1 and 2>, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is equilibrative nucleoside transporters 1 2 reverse transcriptase inhibitor.

HeLa S3 cells express ENT1 and ENT2 and were used to compare relative interactions of these transporters with selected NRTIs. Inhibition of [3H]uridine uptake by NBMPR was biphasic, with IC50 values of 11.3 nM for ENT1 and 9.6娓璏 for ENT2. Uptake measured with 100 nM NBMPR represented ENT2-mediated transport; subtracting that from total uptake represented ENT1-mediated transport. The kinetics of ENT1- and ENT2-mediated [3H]uridine uptake revealed no difference in Jmax (16.53 and 30.40 pmol璺痗m-2璺痬in-1) and an eight-fold difference in Kt (13.6 and 108.9娓璏). The resulting five-fold difference in intrinsic clearance (Jmax/Kt) for ENT1- and ENT2 transport accounted for observed inhibition of [3H]uridine uptake by 100 nM NBMPR. Millimolar concentrations of the NRTIs emtricitabine, didanosine, lamivudine, stavudine, tenofovir disoproxil and zalcitabine had no effect on ENT transport activity, whereas abacavir, entecavir and zidovudine inhibited both transporters with IC50 values of ~200娓璏, 2.5 mM and 2 mM, resp. Using LC-MS/MS and [3H] compounds, the data suggest that entecavir is an ENT substrate, abacavir is an ENT inhibitor, and zidovudine uptake is carrier-mediated, although not an ENT substrate. These data show that HeLa S3 cells can be used to explore complex transporter selectivity and are an adequate model for studying ENTs present at the BTB.

Drug Metabolism & Disposition published new progress about Equilibrative nucleoside transporters, ENT1/SLC29A1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics