JH-II-127

• CAT Number: I002220
• CAS Number: 1700693-08-8
• Molecular Formula: C₁₉H₂₁ClN₆O₃
• Molecular Weight: 416.87
• Purity: ≥95%
• Target: LRRK2
• Solubility: DMSO: ≥ 30 mg/mL
• Storage: -20°C
• IC50: 2.2 n(LRRK2-G2019S), 6.6 nM(LRRK2-wild-type), 47.7 nM (LRRK2-A2016T)
• IUPAC Name: [4-[[5-chloro-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxyphenyl]-morpholin-4-ylmethanone
• InChI: InChI=1S/C19H21ClN6O3/c1-21-16-15-12(20)10-22-17(15)25-19(24-16)23-13-4-3-11(9-14(13)28-2)18(27)26-5-7-29-8-6-26/h3-4,9-10H,5-8H2,1-2H3,(H3,21,22,23,24,25)
• InChIKey: HUEKBQXFNHWTQQ-UHFFFAOYSA-N
• SMILES: CNC1=NC(=NC2=C1C(=CN2)Cl)NC3=C(C=C(C=C3)C(=O)N4CCOCC4)OC

JH-II-127（Cat No.:I002220） is a compound that acts as a highly potent, selective, and brain-penetrant inhibitor of leucine-rich repeat kinase 2 (LRRK2). It exhibits IC50 values of 6.6 nM, 2.2 nM, and 47.7 nM for LRRK2-wild-type, LRRK2-G2019S, and LRRK2-A2016T, respectively. LRRK2 is a protein kinase implicated in neurodegenerative diseases such as Parkinson’s disease. The inhibitory activity of JH-II-127 against LRRK2 suggests its potential for therapeutic development in targeting LRRK2-related disorders.

Reference

1:ACS Med Chem Lett. 2015 Apr 7;6(5):584-9. doi: 10.1021/acsmedchemlett.5b00064. eCollection 2015 May 14. Discovery of a Pyrrolopyrimidine (JH-II-127), a Highly Potent, Selective, and Brain Penetrant LRRK2 Inhibitor.Hatcher JM,Zhang J,Choi HG,Ito G,Alessi DR,Gray NS, PMID: 26005538 PMCID: PMC4434483 DOI: 10.1021/acsmedchemlett.5b00064 Abstract: Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are present in a subset of Parkinson/’s disease (PD) patients and may represent an attractive therapeutic target. Here we report a 2-anilino-4-methylamino-5-chloropyrrolopyrimidine, JH-II-127 (18), as a potent and selective inhibitor of both wild-type and G2019S mutant LRRK2. Compound 18 substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at a concentration of 0.1-0.3 μM in a variety of cell types and is capable of inhibiting Ser935 phosphorylation in mouse brain following oral delivery of doses as low as 30 mg/kg.