HG-10-102-01
Names
[ CAS No. ]:
1351758-81-0
[ Name ]:
HG-10-102-01
[Synonym ]:
[4-[[5-Chloro-4-(methylamino)-2-pyrimidinyl]amino]-3-methoxyphenyl]-4-morpholinylmethanone
(4-{[5-Chloro-4-(methylamino)-2-pyrimidinyl]amino}-3-methoxyphenyl)(4-morpholinyl)methanone
HG-10-102-01
Methanone, [4-[[5-chloro-4-(methylamino)-2-pyrimidinyl]amino]-3-methoxyphenyl]-4-morpholinyl-
Biological Activity
[Description]:
HG-10-102-01 is a potent and selective inhibitor of wild-type LRRK2(IC50=23.3 nM) and the G2019S mutant(IC50=3.2 nM)IC50 Value: 23.3 nM (WT LRRK2); 3.2 nM (LRRK2 G2019S) [1]Target: LRRK2HG-10-102-01 maintains the ability to potently inhibit the biochemical activity of wild-type and G2019S mutant LRRK2. HG-10-102-01 exhibited biochemical IC50s of 20.3 and 3.2 nM against wild-type LRRK2 and LRRK2[G2019S], respectively. At a concentration of 10 μM, HG-10-102-01 only inhibited the kinase activities of MLK1 and MNK2 to greater than 80% of the DMSO control. Dose-response analysis revealed inhibition of MLK1 with an IC50 2.1 μM and MNK2 with an IC50 0.6 μM. KinomeScan analysis against a near comprehensive panel of 451 kinases at a concentration of 1 μM resulted in no interactions detected with kinases other than G2019S LRRK2 with the exception of one mutant form of c-Kit (L576P) demonstrating the outstanding selectivity of this inhibitor.HG-10-102-01 significantly inhibited phosphorylation of wildtype LRRK2 and LRRK2[G2019S] mutant at Ser910 and Ser935 at 0.3-1.0 μM in cell culture, which is approximately the same potency as LRRK2-IN-1 (1). HG-10-102-01 is relatively insensitive to the A2016T mutation which suggests that this mutant will not be useful to validate whether the pharmacological effects of the compound are LRRK2-dependent.HG-10-102-01 can inhibit phosphorylation of Ser910 and Ser935 of LRRK2 in brain and peripheral tissues following intraperitoneal doses of 50 mg/kg. Further optimization of this chemo-type especially in regards to in vivo half-life will be reported in due course [1].
[Related Catalog]:
[References]
[Related Small Molecules]
Chemical & Physical Properties
[ Density]:
1.4±0.1 g/cm3
[ Boiling Point ]:
641.1±65.0 °C at 760 mmHg
[ Molecular Formula ]:
C17H20ClN5O3
[ Molecular Weight ]:
377.825
[ Flash Point ]:
341.5±34.3 °C
[ Exact Mass ]:
377.125458
[ PSA ]:
88.61000
[ LogP ]:
0.46
[ Vapour Pressure ]:
0.0±1.9 mmHg at 25°C
[ Index of Refraction ]:
1.652
[ Storage condition ]:
2-8℃