75 results about "LRRK2" patented technology

Provided are methods for synthesizing compounds having activity against Leucine- rich repeat kinase 2 (LRRK2), as well as intermediates generated during said methods.

This text describes bifunctional compounds that can be used as modulators of non-receptor leucine-rich repeat kinase 2 (LRRK2). In particular, the bifunctional compounds of the present disclosure contain a moiety that binds to the cereblon E3 ubiquitin ligase at one end and a moiety that binds to LRRK2 at the other end, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of the target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities related to degradation / inhibition of the target protein. Treat or prevent diseases or disorders caused by abnormal regulation of the target protein with the compounds and compositions of the present disclosure.

The present invention relates to imidazo[4,5-c]quinoline compounds of Formula (I), and pharmaceutically acceptable salts thereof. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula (I) and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, or inflammatory bowel disease such as Crohn's disease.

The present disclosure relates to bifunctional compounds that cause the degradation of LRRK2; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with LRRK2, including Parkinson's Disease.

This text describes bifunctional compounds that can be used as regulators of leucine-rich repeat kinase 2 (LRRK2). In particular, the heterobifunctional compounds of the present disclosure contain a moiety that binds to the cereblon E3 ubiquitin ligase at one end and a moiety that binds to LRRK2 at the other end, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of the target protein. The heterobifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities related to the degradation / inhibition of the target protein. Treat or prevent diseases or disorders caused by abnormal regulation of the target protein with the compounds and compositions of the present disclosure.

The present disclosure describes methods and compositions involving using LRRK2 mutations as biomarkers for the prediction of immune checkpoint response in cancer and methods and compositions for treating cancers having certain LRRK2 mutations in a subject.

Aspects of the disclosure related to methods of administering LRRK2 inhibitors with peripheral blocker compounds for use in reducing peripheral side effects.

To provide compounds, methods, and pharmaceutical compositions for reducing the amount or activity of leucine-rich repeat kinase (LRRK2) RNA in a cell or animal.SOLUTION: There is provided an oligomeric compound comprising a modified oligonucleotide consisting of 12 to 50 linked nucleosides. Therein: a nucleobase sequence of the modified oligonucleotide is at least 90% complementary to an equal length portion of a LRRK2 nucleic acid; and the modified oligonucleotide comprises at least one modification selected from a modified sugar, a sugar surrogate, and a modified internucleoside linkage.SELECTED DRAWING: None

The present invention is directed to substituted certain N-(heteroaryl)quinazolin-2-amine derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein J, R3, and R4, are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of diseases, such as Parkinson's disease, in which LRRK-2 kinase is involved.

The present disclosure relates to compounds and methods for inhibiting Leucine-Rich Repeat Kinase 2 (LRRK2), the methods comprising administering to the subject a compound of Formula (I). In some embodiments, the disclosure provides compounds and methods for treating cancer.

The present invention provides new inhibitors of LRRK2 / PP1 interaction able to pass through the Blain Blood Barrier and to target the brain. The present invention relates to these inhibitors for use as medicament and more particularly to methods and pharmaceutical compositions for the treatment of neurodegenerative disorders, more particularly α-synucleinopathies.

The present invention is directed to substituted certain N-heteroaryl indazole derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of diseases, such as Parkinson's disease, in which LRRK-2 kinase is involved.

The present application provides a compound shown in formula I, its racemate, stereoisomer, tautomer, isotopically labeled, solvate, polymorph, pharmaceutically acceptable salt or prodrug thereof. Such compounds have good LRRK2 inhibitory effect, and can be used for treating or preventing LRRK2 related diseases and disorders, and preparing drugs for such diseases and disorders.

Bifunctional compounds, which find utility as modulators of non-receptor Leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Method of detecting phosphorylation at Threonine 166 of a Rubicon protein to identify a subject having a disease associated with Leucine-rich repeat kinase 2 (LRRK2) such as Parkinson's disease and compounds and methods for treating the same.

The present invention relates to a pharmaceutical composition for inhibiting the activity of leucine-rich repeat kinase 2 (LRRK2) or for anti-neuroinflammation, and more specifically, to a pharmaceutical composition comprising a Padina arborescens extract as an active ingredient for inhibiting the activity of leucine-rich repeat kinase 2 (LRRK2) or for anti-neuroinflammation. According to the present invention, the risk of developing diseases and neuroinflammation due to the activity of the LRRK2 kinase is reduced, and the LRRK2 kinase can be utilized in medicines, foods, quasi-drugs, etc. for preventing, alleviating, and treating diseases and neuroinflammation due to the activity of the LRRK2 kinase.

The present invention relates to a novel compound as shown in formula (I) and a pharmaceutically acceptable salt thereof, said compound being capable of inhibiting leucine-rich repeat kinase 2 (LRRK2), and a pharmaceutically acceptable salt thereof, said compound being capable of inhibiting leucine-rich repeat kinase 2 (LRRK2); the invention also relates to pharmaceutical compositions thereof, processes for their preparation and therapeutic uses.

The present disclosure relates generally to LRRK2 inhibitors, or a pharmaceutically acceptable salt, isotopically enriched analog, tautomer, stereoisomer, mixture of stereoisomers, prodrug, or pharmaceutical composition thereof, and methods of making and using thereof.

The invention relates to the technical field of dyskinesia, in particular to application and a system of a gene marker combination in preparation of a Parkinson's disease dyskinesia risk assessment product, and the gene marker combination comprises COMT rs4680, MAOB rs1799836, GBA, DRD2 rs2283265, DRD3 rs6280, LRRK2 G2385R, BDNF rs6265, HOMER1 rs4704559 and SLC6A3 rs28363170. Wherein the product is used for calculating the dyskinesia risk value by detecting the genotype of the gene marker. According to the method, nine genetic markers and multi-modal clinical data are integrated, the risk probability is dynamically calculated based on the Bayesian algorithm, an individual intervention scheme is output, and early-stage accurate prevention and control are achieved.

The invention provides methods of treating patients with Parkinson's disease (PD) associated with wild-type LRRK2. The invention recognizes that analysis of biomarkers in such patients allows identification of those patients who will respond to LRRK2 inhibitors. Thus, the invention provides methods of identifying PD patients who will respond to LRRK2 inhibitors and methods of treating such patients.

The present invention relates to an indazole derivative and a preparation method therefor and a use thereof. The indazole derivative can be used for LRRK2 kinase inhibition or for treating Parkinson's disease (PD).

The present disclosure relates generally to LRRK2 inhibitors, or a pharmaceutically acceptable salt, deuterated analog, prodrug, tautomer, stereoisomer, or mixture of stereoisomers thereof, and methods of making and using thereof. 20 24 20 46 21 03 J ul 2 02 4 1 0 0 5 3 7 4 6 8 9 A B S T R A C T 2 0 2 4 2 0 4 6 2 1 0 3 J u l 2 0 2 4

Compounds having the formula I, II, or III: are provided. Compounds of the present disclosure are useful for the treatment of neurodegenerative diseases, such as Parkinson's Disease.

The present disclosure describes synthetic polypeptides for the inhibition or modulation of the activity of leucine-rich repeat kinase 2 (LRRK2) along with methods of using the same in the treatment of medical conditions, for example neurological diseases or disorders.

The invention relates to a novel compound as shown in a formula (I) and a pharmaceutically acceptable salt of the novel compound. The compound can be used for inhibiting leucine-rich repeat kinase 2 (LRRK2), and can be used for inhibiting leucine-rich repeat kinase 2 (LRRK2), leucine-rich repeat kinase 2 (LRRK2) and leucine-rich repeat kinase 2 (LRRK2). The invention also relates to pharmaceutical compositions thereof, processes for their preparation and therapeutic uses.