LRRK2 Inhibitor

MLi-2, a chemical probe, is an orally active and highly selective LRRK2 inhibitor with an IC₅₀ of 0.76 nM. MLi-2 has the potential for Parkinson’s disease.

IKK 16 is an orally active IKK inhibitor. IKK 16 shows IC₅₀s of 40 nM, 70 nM, 200 nM, and 50 nM for IKK2, IKK complex, IKK1, and LRRK 2, respectively. IKK 16 is also a pan-PKD inhibitor, inhibiting PKD1, PKD2, and PKD3 with IC₅₀s of 153.9, 115, and 99.7 nM, respectively. IKK 16 is also an ABCB1 inhibitor, interfering with the binding of ABCB1 to its substrates. IKK 16 protects against LPS (HY-D1056)-induced multiple organ dysfunction by reducing the acute inflammatory response induced by endotoxin exposure. IKK 16 can restore renal function and alleviate fibrosis in acute kidney injury. IKK 16 attenuates cardiac dysfunction associated with polymicrobial sepsis in mice with type 2 diabetes mellitus (T2DM) by inhibiting the NF-κB pathway.

LRRK2-IN-1 is a potent and selective LRRK2 inhibitor with IC₅₀ of 6 nM and 13 nM for LRRK2 (G2019S) and LRRK2 (WT), respectively.

Indazole, also called isoindazole, a heterocyclic aromatic organic compound. Its derivatives display a broad variety of biological activities including anti-inflammatory, antibacterial, anti-HIV, antiarrhythmic, antifungal and antitumour properties. Indazole and its derivatives can be used for research of cancer, neurological disorders, cardiovascular diseases, gastrointestinal diseases.

LRRK2-IN-22 is a LRRK2 inhibitor, with IC₅₀ values of 315.7 nM and 255.4 nM against LRRK2^WT and LRRK2^G2019S, respectively. LRRK2-IN-22 effectively inhibits LRRK2 kinase activity and downstream Rab10 phosphorylation, reduces ROS, and exhibits low cytotoxicity. LRRK2-IN-22 can be used for research on Parkinson's disease.

LRRK2/JNK3-IN-1 is a brain-penetrant multi-target inhibitor of LRRK2 (including G2019S mutant and wild-type) and JNK3, with enzymatic IC₅₀ values of 3.90 nM against LRRK2^G2019S, 3.24 nM against wild-type LRRK2, and 22.1 nM against JNK3. LRRK2/JNK3-IN-1 displays favorable selectivity in a 97-kinase profiling screen, and also shows inhibitory activity against JNK1, JNK2, and MKNK2. LRRK2/JNK3-IN-1 can be used for the research of Parkinson's disease.

PF-06447475 is a highly potent, selective and brain penetrant LRRK2 inhibitor with an IC₅₀ of 3 nM.

GNE0877 is a highly selective, orally active and brain-penetrant LRRK2 inhibitor with an IC₅₀ of 3 nM and a K_i of 0.7 nM. GNE0877 can be used for the research of neuroscience.

GSK2578215A is a potent and highly selective LRRK2 inhibitor, which exhibits IC₅₀s of around 10 nM against both wild-type LRRK2 and the G2019S mutant.

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

IKK 16 hydrochloride is an orally active IKK inhibitor. IKK 16 hydrochloride shows IC₅₀s of 40 nM, 70 nM, 200 nM, and 50 nM for IKK2, IKK complex, IKK1, and LRRK 2, respectively. IKK 16 hydrochloride is also a pan-PKD inhibitor, inhibiting PKD1, PKD2, and PKD3 with IC₅₀s of 153.9, 115, and 99.7 nM, respectively. IKK 16 hydrochloride is also an ABCB1 inhibitor, interfering with the binding of ABCB1 to its substrates. IKK 16 hydrochloride protects against LPS (HY-D1056)-induced multiple organ dysfunction by reducing the acute inflammatory response induced by endotoxin exposure. IKK 16 hydrochloride can restore renal function and alleviate fibrosis in acute kidney injury. IKK 16 hydrochloride attenuates cardiac dysfunction associated with polymicrobial sepsis in mice with type 2 diabetes mellitus (T2DM) by inhibiting the NF-κB pathway.

HG-10-102-01 is a highly potent, selective, and brain-penetrable LRRK2 inhibitor, with IC₅₀ values of 20.3 and 3.2 nM against wild-type LRRK2 and LRRK2[G2019S], respectively. HG-10-102-01 also inhibits MNK2 and MLK1, with IC₅₀ values of 0.6 and 2.1 μM. HG-10-102-01 can be used for Parkinson's disease (PD) research.

PFE-360 (PF-06685360) is a potent, selective, brain penetrated and orally active leucine-rich repeat kinase 2 (LRRK2) inhibitor with a mean IC₅₀ of 2.3 nM in vivo.

CZC-25146 is a potent and orally active LRRK2 inhibitor with IC₅₀ values of 4.76 nM and 6.87 nM for wild-type LRRK2 and G2019S LRRK2, respectively. CZC-25146 inhibits PLK4, GAK, TNK1, CAMKK2 and PIP4K2C as well. CZC-25146 prevents mutant LRRK2-induced injury of neurons in vitro. CZC-25146 exhibits relatively favorable pharmacokinetic properties in mice. CZC-25146 can increase normal α-1-antitrypsin (AAT) secretion and reduce inflammatory cytokines. CZC-25146 can be used to research Parkinson's disease and liver diseases.

GNE-9605 is a potent, orally active, selective Leucine-rich repeat kinase 2 (LRRK2) inhibitor with an IC₅₀ value of 18.7 nM. GNE-9605 inhibits LRRK2 Ser1292 autophosphorylation. GNE-9605 can be used in research of Parkinson's disease (PD) .

LRRK2 inhibitor 1 is a LRRK2 inhibitor. LRRK2 inhibitor 1 blocks STAT1 phosphorylation and the expression of interferon-stimulated genes, and inhibits intracellular innate immune responses. LRRK2 inhibitor 1 enhances oncolytic virus infection, replication and viral protein expression in tumor cells, promotes tumor cell apoptosis, and cooperates with oncolytic viruses to reduce tumor cell viability. LRRK2 inhibitor 1 enhances the oncolytic activity of multiple oncolytic viruses, and inhibits the growth of glioma xenografts when used in combination with oncolytic viruses. LRRK2 inhibitor 1 can be used in research related to various cancers such as lung cancer, colorectal cancer and liver cancer.

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.

MK-1468 is an orally active, selective, and BBB-permeable LRRK2 inhibitor. MK-1468 can be used for the research of Parkinson's disease.

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

EB-42486 is a novel, potent, and highly selective G2019S-LRRK2 inhibitor (IC₅₀: < 0.2 nM). EB-42486 can be used in the research of Parkinson's disease.