2-피리딘카르복사미드,6-aMino-N-메틸-5-(2,3,5-트리클로로페닐)-

2-피리딘카르복사미드,6-aMino-N-메틸-5-(2,3,5-트리클로로페닐)- 속성

2-피리딘카르복사미드,6-aMino-N-메틸-5-(2,3,5-트리클로로페닐)- C화학적 특성, 용도, 생산

개요

PF-01247324 is a blocker of the tetrodotoxin-resistant (TTX-R) sodium channel Na_v1.8 (IC₅₀ = 0.19 μM for human Na_v1.8). It is selective for Na_v1.8 over Na_v1.1, Na_v1.2, Na_v1.5, and Na_v1.7 channels (IC₅₀s = 13, 12.8, 9, and 19 μM, respectively) as well as ether-a-go-go (ERG) potassium channels (IC₅₀ = 30 μM). PF-01247324 blocks Na_v1.8 channels in a VSP-FRET assay using HEK293 cells (IC₅₀ = 2.6 μM). In vivo, PF-01247324 (100 mg/kg) reduces phase 2 flinching in a rat model of formalin-induced persistent pain. It increases latency to lift the inflamed paw and latency to paw withdrawal in rat models of carrageenan-induced thermal hyperalgesia and mechanical hyperalgesia induced by complete Freund''s adjuvant (CFA), respectively.

Biochem/physiol Actions

In humans, PF-01247324 [6-amino-5-(2, 3, 5-trichloro-phenyl)-pyridine-2-carboxylic acid methylamide] prevents native tetrodotoxin-resistant (TTX-R) currents in dorsal root ganglion (DRG) neurons.

효소 저해제

This novel oral NaV1.8 blocker (FW = 330.59 g/mol) attenuates nociception and neuronal excitability by selectively targeting voltage-gated sodium transporter NaV1.8, with much weaker action against NaV1.1, NaV1.2, NaV1.4, NaV1.5, NaV1.6, and NaV1.7 transporters. PF-01247324 inhibited native tetrodotoxin-resistant (TTX-R) currents in human dorsal root ganglion (DRG) neurons (IC50 = 331 nM) and in recombinantly expressed hNav 1.8 (IC50 = 196 nM), with 50-fold selectivity over recombinantly expressed TTX-R hNav 1.5 channels (IC50 ～ 10 μM) and 65-100 greater selectivity over TTX-sensitive (TTX-S) channels (IC50 ～ 10-18 μM). Native TTX-R currents in small diameter rodent DRG neurons were inhibited with an IC50 of 448 nM, and the block of both human recombinant Nav1.8 and TTX-R from rat DRG neurons was both frequency and statedependent. Unlike previously published NaV1.8 blockers, PF-01247324 demonstrates frequency-dependence, and off-target frequency-dependence at other sodium channel subtypes may reduce its selectivity window. The majority of small molecule sodium channel blockers interact at the local anesthetic binding site, which due to a high level of sequence homology across voltage-gated sodium channel subtypes seems an unlikely site for interaction of selective agents such as PF-01247324. The majority of small molecule sodium channel blockers interact at the local anesthetic binding site, which due to a high level of sequence homology across voltage-gated sodium channel subtypes seems an unlikely site for interaction of selective agents such as PF-01247324

2-피리딘카르복사미드,6-aMino-N-메틸-5-(2,3,5-트리클로로페닐)- 준비 용품 및 원자재

원자재

준비 용품

2-피리딘카르복사미드,6-aMino-N-메틸-5-(2,3,5-트리클로로페닐)- 공급 업체

공급자	전화	이메일	국가	제품 수	이점
ATK CHEMICAL COMPANY LIMITED	+undefined-21-51877795	ivan@atkchemical.com	China	32715	60
InvivoChem	+1-708-310-1919 +1-13798911105	sales@invivochem.cn	United States	6393	58
TargetMol Chemicals Inc.	+1-781-999-5354	support@targetmol.com	United States	19973	58
ShenZhen Trendseen Biological Technology Co.,Ltd.	13417589054	trendseenbio@gmail.com	China	11681	58
Amadis Chemical Company Limited	571-89925085	sales@amadischem.com	China	131980	58
ChemShuttle, Inc.	0510-83588313-802 18800520310;	sales@chemshuttle.com	China	2968	62
Modachem Shanghai Co., Ltd	+86 (0)21 51320687 51371369 1744605818		China	1579	58
Sigma-Aldrich	021-61415566 800-8193336	orderCN@merckgroup.com	China	51471	80
Shanghai Lollane Biological Technology Co.,Ltd.	021-52996696，15000506266 15000506266		China	4182	55
AOKBIO Inc.	021-68712331 3286104197		China	323	55

2-피리딘카르복사미드,6-aMino-N-메틸-5-(2,3,5-트리클로로페닐)- 관련 검색: