LRRK2 Inhibitor

JH-II-127 is an orally active, highly potent, selective and brain-permeable LRRK2 inhibitor, with IC₅₀s of 6, 2 and 48 nM for wild-type LRRK2 and LRRK2-G2019S and mutant LRRK2-A2016T. JH-II-127 inhibits Ser935 phosphorylation in all tissues of mice, including the brain. JH-II-127 can be used in the study of parkinson's syndrome.

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

GSK2646264 (Compound 44) is a potent and selective spleen tyrosine kinase (SYK) inhibitor with a pIC₅₀ of 7.1. GSK2646264 also inhibits other kinases with pIC₅₀ values of 5.4, 5.4, 5.3, 5, 4.5, <4.6 and <4.3 against LCK, LRRK2, GSK3β, JAK2, VEGFR2, Aurora B and Aurora A, respectively. GSK2646264 is penetrable into the epidermis and dermis of the skin.

PF-06447475 is a highly potent, selective, brain penetrant LRRK2 kinase inhibitor with IC₅₀ values of 3 nM and 11 nM for WT LRRK and G2019S LRRK2, respectively. PF-06447475 can be used for parkinson's disease (PD) research.

SRI-31255 is an orally active LRRK2 inhibitor with IC₅₀ values of 520 and 427 nM for human wild-type (WT) and mutant G2019S, respectively. SRI-31255 exerts neuroprotective effects by binding to the ATP-binding pocket of LRRK2, inhibiting kinase activity. SRI-31255 can be used as a lead compound for the development of LRRK2-targeted drugs for the treatment of Parkinson's disease.

RN341 is a specific type II kinase inhibitor of LRRK2 (IC₅₀: 296 nM). RN341 inhibits LRRK2 phosphorylation and avoids S935 dephosphorylation by stabilizing the open conformation. RN341 rescues LRRK2-mediated kinesin motility block by preventing microtubule binding. RN341 effectively inhibits LRRK2 wild-type and G2019S mutant at the cellular level. RN341 provides a new direction for Parkinson's disease research.

PF-06455943 is a leucine rich repeat kinase 2 (LRRK2) inhibitor with IC₅₀ value of 3 nM. PF-06455943 also is a PET radioligand. PF-06455943 can be used for the research of ADME/neuro PK characterization and Parkinson disease (PD).

(R,R)-LRRK2-IN-7 is the isomer of LRRK2-IN-7 (HY-152107). LRRK2-IN-7 is a potent, selective, and CNS-penetrant LRRK2 kinase inhibitor with an IC50 of 0.9 nM. LRRK2-IN-7 shows >1000-fold selectivity over other kinases, ion channels, and CYP enzymes.

LRRK2-IN-2 (compoubd 22) is a potent, selective, orally active and brain-penetrant inhibitor LRRK2, with IC₅₀ of <0.6 nM. LRRK2-IN-2 can be used for the research of Parkinson's disease.

LRRK2-IN-8 is a LRRK2 inhibitor. LRRK2-IN-8 inhibits LRRK2 (wt) and LRRK2 (G2019) with IC₅₀s lower than 10 nM, and inhibits TYK2 and NUAK1 with IC₅₀s of 10-100 nM.

LRRK2-IN-3 (compoubd 24) is a potent, selective, orally active and brain-penetrant inhibitor LRRK2, with IC₅₀ of 2.6 nM in human PBMCs. LRRK2-IN-3 can be used for the research of Parkinson's disease.

LRRK2-IN-17 (Compound 6) is an orally active LRRK2 inhibitor (IC₅₀: 3.5 and 3.3 nM for WT and G2019S, respectively). LRRK2-IN-17 inhibits RET kinase (IC₅₀: 59 nM). LRRK2-IN-17 can be used in cancer and Parkinson's disease (PD) research.

LRRK2-IN-16 (compound 25) is a LRRK2 kinase inhibitor with an IC₅₀ < 5 μM. LRRK2-IN-16 can be utilized in neurodegenerative disorders and autoimmune disorders research.

LRRK2-IN-10 (compound 34) is a potent, mutation-selective, and brain penetrant G2019S-LRRK2 kinase inhibitor with IC₅₀s of 11 nM and 5.2 nM for G2019S-LRRK2 pS935 and G2019S-LRRK2 pS1292, respectively. LRRK2-IN-10 has the potential for Parkinson's disease research.

CZC-54252 hydrochloride is a potent and selective LRRK2 inhibitor with IC₅₀s of 1.28 nM and 1.85 nM for wild-type and G2019S LRRK2, respectively. G2019S LRRK2-induced human neuronal injury is attenuated by CZC-54252 hydrochloride with an EC₅₀ of ~1 nM.CZC-54252 hydrochloride has a neuroprotective activity.

Lu AF58786 is a potent and selective LRRK2 inhibitor with an IC₅₀ of 12 nM. Lu AF58786 also exhibits inhibition activity against LRRK2 G2019S and LRRK2 A2016T with IC₅₀s of 19 and 93 nM. Lu AF58786 inhibits phosphorylation of LRRK2, Rab10 and Rab12 in human peripheral blood mononuclear cells. Lu AF58786 can be used for parkinson’s disease research.

LRRK2-IN-14 (Compound 8) is an orally active LRRK2 inhibitor. LRRK2-IN-14 has an IC₅₀ of 6.3 nM for LRRK2(G2019S) cell activity.LRRK2-IN-14 has an inhibitory effect on hERG (IC₅₀=22 μM). LRRK2-IN-14 has blood-brain barrier permeability.

LRRK2/NUAK1/TYK2-IN-1 (conpound 226) shows inhibitory activity toward LRRK2 (Wt), LRRK2 (G2019), TYK2 and NUAK1, with IC₅₀ values lower than 10 nM. LRRK2/NUAK1/TYK2-IN-1 can be used for autoimmune disease research.

LRRK2-IN-6 (compound 22) is a potent, orally active, selective leucine rich repeat protein kinase 2 gene (LRRK2) inhibitor with IC₅₀ values of 4.6 and 49 μM for GS LRRK2 and WT LRRK2, respectively. LRRK2-IN-6 inhibits LRRK2 Ser1292 and Ser925 autophosphorylation. LRRK2-IN-6 can cross the blood-brain barrier.

SRI-29132 is a potent leucine-rich repeat kinase 2 (LRRK2) inhibitor. SRI-29132 is promising for research of Parkinson’s disease.