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GNE7915

Names

[ CAS No. ]:
1351761-44-8

[ Name ]:
GNE7915

[Synonym ]:
gne 7915
(4-{[4-(Ethylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino}-2-fluoro-5-methoxyphenyl)(4-morpholinyl)methanone
Methanone, [4-[[4-(ethylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino]-2-fluoro-5-methoxyphenyl]-4-morpholinyl-

Biological Activity

[Description]:

GNE-7915 is a potent, selective and brain-penetrant inhibitor of LRRK2 with an IC50 of 9 nM.

[Related Catalog]:

Signaling Pathways >> Autophagy >> LRRK2
Research Areas >> Neurological Disease

[Target]

IC50: 9 nM[1] (LRRK2)


[In Vitro]

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[2].

[References]

[1]. Kavanagh ME, et al. The development of CNS-active LRRK2 inhibitors using property-directed optimisation. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3690-6.

[2]. Estrada AA, et al. Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. J Med Chem. 2012 Nov 26;55(22):9416-33.


[Related Small Molecules]

LRRK2-IN-1 | IKK-16 | MLi-2 | PF-06447475 | GSK2578215A | GNE-9605 | CZC-54252 | GNE-0877 | HG-10-102-01 | JH-II-127 | CZC 25146

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
629.9±65.0 °C at 760 mmHg

[ Molecular Formula ]:
C19H21F4N5O3

[ Molecular Weight ]:
443.395

[ Flash Point ]:
334.7±34.3 °C

[ Exact Mass ]:
443.158051

[ PSA ]:
88.61000

[ LogP ]:
1.81

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.578

[ Storage condition ]:
2-8℃


Related Compounds