Saltar al contenido
Merck

In vitro Characterization of a small molecule inhibitor of the alanine serine cysteine transporter -1 (SLC7A10).

Journal of neurochemistry (2013-11-26)
Jeffrey M Brown, Lisa Hunihan, Margaret M Prack, David G Harden, Joanne Bronson, Carolyn D Dzierba, Robert G Gentles, Adam Hendricson, Rudy Krause, John E Macor, Ryan S Westphal
RESUMEN

NMDA receptor hypofunction is hypothesized to contribute to cognitive deficits associated with schizophrenia. Since direct activation of NMDA receptors is associated with serious adverse effects, modulation of the NMDA co-agonists, glycine or D-serine, represents a viable alternative therapeutic approach. Indeed, clinical trials with glycine and D-serine have shown positive results, although concerns over toxicity related to the high-doses required for efficacy remain. Synaptic concentrations of D-serine and glycine are regulated by the amino acid transporter alanine serine cysteine transporter-1 (asc-1). Inhibition of asc-1 would increase synaptic D-serine and possibly glycine, eliminating the need for high-dose systemic D-serine or glycine treatment. In this manuscript, we characterize Compound 1 (BMS-466442), the first known small molecule inhibitor of asc-1. Compound 1 selectively inhibited asc-1 mediated D-serine uptake with nanomolar potency in multiple cellular systems. Moreover, Compound 1 inhibited asc-1 but was not a competitive substrate for this transporter. Compound 1 is the first reported selective inhibitor of the asc-1 transporter and may provide a new path for the development of asc-1 inhibitors for the treatment of schizophrenia.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Glicina, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
Glicina, suitable for electrophoresis, ≥99%
Sigma-Aldrich
Glicina, BioUltra, for molecular biology, ≥99.0% (NT)
Sigma-Aldrich
L-Histidina, suitable for cell culture, meets EP, USP testing specifications, from non-animal source
Sigma-Aldrich
L-Serine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
L-Serine, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
Glicina, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, ≥98.5%
SAFC
Glicina
Sigma-Aldrich
Glycine hydrochloride, ≥99% (HPLC)
Sigma-Aldrich
L-Histidina, BioUltra, ≥99.5% (NT)
SAFC
L-Histidina
USP
Glicina, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Glicina, BioXtra, ≥99% (titration)
Sigma-Aldrich
L-Serine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
L-Histidina, ReagentPlus®, ≥99% (TLC)
Sigma-Aldrich
Glicina, 99%, FCC
Sigma-Aldrich
Glicina, SAJ special grade, ≥99.0%
Sigma-Aldrich
Glicina, ACS reagent, ≥98.5%
L-Histidina, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Glicina, meets analytical specification of Ph. Eur., BP, USP, 99-101% (based on anhydrous substance)
Supelco
Glicina, Pharmaceutical Secondary Standard; Certified Reference Material
Serine, European Pharmacopoeia (EP) Reference Standard
Supelco
L-Histidina, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
L-Serine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
BMS-466442, ≥98% (HPLC)
Glicina, European Pharmacopoeia (EP) Reference Standard
Supelco
L-Histidina, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
Glicina, tested according to Ph. Eur.
Supelco
L-Serine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland