22 results about "LRRK2" patented technology

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.

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.

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 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 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

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.

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

The present invention refers to an oligonucleotide comprising 10 to 25 nucleotides, at least one nucleotide having a modification, wherein the oligonucleotide hybridizes with a transcript or an mRNA of leucine-rich repeat kinase 2 (LRRK2) of SEQ ID NO. 1 and / or with pre-mRNA of LRRK2 of SEQ ID NO. 2 and / or a fragment thereof. The invention further refers to a pharmaceutical composition comprising such oligonucleotide, and the use of the oligonucleotide and pharmaceutical composition, respectively, for use in method of preventing and / or treating a human disease.

The present invention is directed to certain 2-aminoquinzaoline derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R3, R4, X1, and X2 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 such diseases in which LRRK-2 kinase is involved.

Compounds having activity as inhibitors of LRRK2 kinase are provided. The compounds have Structure (I):or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R1a, R1b, R2, and L are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of LRRK2 kinase are also provided.

Disclosed herein are compounds that inhibit leucine-rich repeat kinase 2 (LRRK2), pharmaceutical compositions comprising the compounds, and methods of using the compounds, e.g., in a method of treating a disorder that derives in full or in part from LRRK2 kinase activity, such as neurodegenerative diseases, immune-mediated diseases, and forms of cancer.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a leucine-rich repeat kinase 2 (LRRK2) gene, as well as methods of inhibiting expression of a LRRK2 gene and methods of treating subjects having a LRRK2-associated disease or disorder, e.g., Parkinson's disease, using such dsRNAi agents and compositions.

Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-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 hetero-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.

The present disclosure provides optionally modified small interfering ribonucleic acid (siRNA) compounds, pharmaceutical compositions, and methods of use thereof. The optionally modified siRNA compounds may be tailored to improve delivery to the central nervous system, to reduce off-target effects, and / or to reduce expression of mRNA transcribed from a gene of interest (e.g., LRRK2, VEGFA, or ANGPT2), i.e., to translate to a protein. In some embodiments, the sense strand of the siRNA comprises a synthetic nucleotide and / or a lipid conjugated to one or both ends of the sense strand, or within any position of the sense strand.

This application discloses a compound that has inhibitory activity against LRRK2. This application also discloses a pharmaceutical composition comprising the compound and a method of treating diseases and conditions using the compound, said diseases and conditions including neurodegenerative diseases and conditions such as Parkinson's disease and brain cancers (e.g., glioma and glioblastoma).

The present invention relates to a macrocyclic pyrimidine derivative, a method for preparing the same, and a pharmaceutical composition for the prevention or treatment of a neurodegenerative disease, containing the same as an active ingredient. The macrocyclic pyrimidine derivative according to the present invention has excellent LRRK2 inhibitory activity and efficiently penetrates the blood-brain barrier (BBB), and thus can be effectively used as a pharmaceutical composition for the prevention or treatment of a neurodegenerative disease.

The invention relates to an aminopyrimidine derivative as well as a preparation method and application thereof. The aminopyrimidine derivative can be used for inhibiting LRRK2 kinase or treating Parkinson's disease (PD).