GNE-7915 tosylate

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GNE-7915 tosylate (GNE7915 tosylate) 是一种高效、选择性、脑可渗透的 LRRK2 抑制剂，IC50 为 1.9 nM。

GNE-7915 tosylate (GNE7915 tosylate) is a highly potent, selective, and brain-penetrable LRRK2 inhibitor with IC50 of 1.9 nM; shows 1/187 kinases with 50% inhibition at 0.1 uM; possesses an ideal balance of LRRK2 cellular potency, broad kinase selectivity, metabolic stability, and brain penetration across multiple species.Parkinson's Disease Preclinical.

Maintaining the methoxy/fluoro arrangement at C-2′/C-5′ and varying aminoalkyl R1 substitution resultes in single-digit nanomolar LRRK2 cellular activities for GNE-7915 and compound 19. Expanded Invitrogen kinase profiling (187 kinases) at 0.1 μM for both GNE-7915 (100-fold over LRRK2 Ki) and 19 (250-fold over LRRK2 Ki) resultes in only TTK showing greater than 50% inhibition. Selectivity profiling using the DiscoverX KinomeScan55 competitive binding assay panel, which includes 392 unique kinases, is also performed for GNE-7915 at 0.1 μM. Binding of >50% probe displacement is detected for 10 kinases and of >65% for only LRRK2, TTK, and ALK, further supporting the excellent LRRK2 selectivity for GNE-7915. Cerep receptor profiling, including expanded brain panels, suggestes that GNE-7915 and 19 only inhibite 5-HT2B with >70% inhibition at 10 μM. GNE-7915 and 19 are confirmed to be moderately potent 5-HT2B antagonists in vitro functional assays.

——

GNE7915 tosylate | GNE 7915 tosylate

Autophagy

LRRK2

LRRK2

Neurological Disease

Parkinson Disease

2070015-00-6

615.597

C26H29F4N5O6S

>98% (HPLC)

10 mM in DMSO

CCNC1=NC(=NC=C1C(F)(F)F)NC2=C(C=C(C(=C2)F)C(=O)N3CCOCC3)OC.CC1=CC=C(C=C1)S(=O)(=O)O

Methanone, [4-[[4-(ethylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino]-2-fluoro-5-methoxyphenyl]-4-morpholinyl-, 4-methylbenzenesulfonate (1:1)

(-20℃)

With Ice Pack

≥ 2 years