Novel N-Linked Isoquinoline Amides as LRRK2 Inhibitors for Treating Parkinson’s Disease

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• The luminance of a lighthouse January 24, 2022 # # # # LRRK2 inhibition represents one of several biological approaches to slowing the progression of Parkinson’s that is currently being clinically tested. Leading the charge in the development of LRRK2 inhibitors is a biotech company called Denali Therapeutics (in partnership with Biogen). Recently, the company provided news on the immediate future clinical development plans for their lead molecule…
• Denali’s Phase I results May 27, 2021 # # # # Leucine-rich repeat kinase 2 (or LRRK2) is a large, multi function protein that is associated with Parkinson’s. People with genetic variations in the region of DNA that provides the instructions for making LRRK2 protein have a higher risk of developing the condition. In many cases of Parkinson’s, LRRK2 can become hyperactive. Researchers and biotech companies have…
• The road ahead: 2022 January 20, 2022 # # # # The first post at the start of each year on the SoPD website tries to provide an overview of where things are in the search for ‘disease modifying’ therapies for Parkinson’s.  It is an exercise in managing expectations as well as discussing what research events are scheduled for the next year so that we can keep…
• The Llama-nation of LRRK2 April 8, 2022 # # # # Antibodies are tiny y-shaped markers used by the immune system to label foreign agents within the body. Once bound to something, antibodies can alert immune cells to come and remove the object. Antibodies can also inhibit the object from doing anything nasty, like infecting or damaging a cell. Between species, different types of antibodies have been…
• Something LRRKing in the immune system October 12, 2019     Canadian scientists recently reported that mice with a specific genetic variation – in the Parkinson’s-associated LRRK2 gene – differ in how they are able to deal with bacterial and viral infections. Curiously, mice with the Parkinson’s-associated LRRK2 mutation could handle a bacterial infection better than normal mice, while mice with no LRRK2 protein struggled against the infection. And…
• The Lords of LRRK December 25, 2019   Here on the SoPD we have discussed the Parkinson’s-associated protein LRRK2 many times. And we look forward to seeing the results of ongoing clinical trials of LRRK2 inhibitors. But there are significant efforts ongoing to develop therapies that can indirectly target dysfunctional LRRK2 pathways (which may help avoid any potential side effects of direct inhibition) Recently, researchers in Scotland…
• The road ahead: 2021 January 25, 2021 # # # # At the start of each year, it is a useful practise to layout what is planned over the next 12 months. The events that are scheduled for the year to come, so that we can keep an eye out for them. Obviously, where 2021 will end actually is unpredictable, but an outline of what is scheduled…
• Novel N-Linked Isoquinoline Amides as LRRK2 Inhibitors for Treating Parkinson's Disease August 5, 2022 ACS Med Chem Lett. 2022 Jun 21;13(7):1008-1009. doi: 10.1021/acsmedchemlett.2c00263. eCollection 2022 Jul 14.NO ABSTRACTPMID:35928851 | PMC:PMC9345376 | DOI:10.1021/acsmedchemlett.2c00263
• Novel N-Linked Isoquinoline Amides as LRRK2 Inhibitors for Treating Parkinson's Disease August 5, 2022 ACS Med Chem Lett. 2022 Jun 21;13(7):1008-1009. doi: 10.1021/acsmedchemlett.2c00263. eCollection 2022 Jul 14.NO ABSTRACTPMID:35928851 | PMC:PMC9345376 | DOI:10.1021/acsmedchemlett.2c00263
• Novel N-Linked Isoquinoline Amides as LRRK2 Inhibitors for Treating Parkinson's Disease August 5, 2022 ACS Med Chem Lett. 2022 Jun 21;13(7):1008-1009. doi: 10.1021/acsmedchemlett.2c00263. eCollection 2022 Jul 14.NO ABSTRACTPMID:35928851 | PMC:PMC9345376 | DOI:10.1021/acsmedchemlett.2c00263
• Novel N-Linked Isoquinoline Amides as LRRK2 Inhibitors for Treating Parkinson's Disease August 5, 2022 ACS Med Chem Lett. 2022 Jun 21;13(7):1008-1009. doi: 10.1021/acsmedchemlett.2c00263. eCollection 2022 Jul 14.NO ABSTRACTPMID:35928851 | PMC:PMC9345376 | DOI:10.1021/acsmedchemlett.2c00263
• Novel N-Linked Isoquinoline Amides as LRRK2 Inhibitors for Treating Parkinson's Disease August 5, 2022 ACS Med Chem Lett. 2022 Jun 21;13(7):1008-1009. doi: 10.1021/acsmedchemlett.2c00263. eCollection 2022 Jul 14.NO ABSTRACTPMID:35928851 | PMC:PMC9345376 | DOI:10.1021/acsmedchemlett.2c00263
• The Tau of LRRK2 December 3, 2019   Dense spherical clusters of a protein – called Lewy bodies – are one of the classical hallmarks of the Parkinsonian brain. They are a common pathological feature, but curiously they are not present in all cases of Parkinson’s. For example, some individuals with certain forms of Parkinson’s associated with specific genetic mutations do not exhibit any Lewy bodies. Variations…
• Unmasking LRRK2 and GBA May 22, 2021 # # # # Connecting genetics and biology is complicated. Researchers around the world have struggled to determine what each functional region of DNA is doing individually, let alone in combination with other regions. And sometimes when the output of combinations is examined, the results can be unexpected. Recently, researchers looked at the consequences of having a particular combination of…
• ROPAD + LIPAD = NOT BAD 🙂 December 10, 2019       Approximately 10-20% of Parkinson’s cases are associated with a genetic risk factor which raises the chances of developing the condition. Tremendous efforts are being made to not only better understand the underlying biology of these associations, but also to identify individuals who may be affected and invite them to take part in innovative new clinical trials. The…
• The road ahead: 2020 January 5, 2020 Here at the SoPD, we are primarily interested in disease modification for Parkinson’s. While there is a great deal of interesting research exploring the causes of the condition, novel symptomatic therapies, and other aspects of Parkinson’s, my focus is generally on the science seeking to slow, stop or reverse the condition. At the start of each year, it is a…
• Monthly Research Review – September 2021 September 30, 2021 # # # # At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during September 2021. The post is divided into 10 parts based on the type of research: Top 4 pieces of Parkinson’s news Articles of general interest Basic biology…
• Monthly Research Review – November 2020 November 30, 2020   At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during November 2020. The post is divided into seven parts based on the type of research: Basic biology Disease mechanism Clinical research New clinical trials Clinical trial news Conferences/lectures Other news…
• Monthly Research Review – June 2021 June 30, 2021 # # # # At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during June 2021. The post is divided into 10 parts based on the type of research: Top 4 pieces of Parkinson’s news Articles of general interest Basic biology…
• Monthly Research Review – December 2021 December 31, 2021 # # # # At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during December 2021. The post is divided into 10 parts based on the type of research: Top 5 pieces of Parkinson’s news Articles of general interest Basic biology…
• Five Takeaways from Our LRRK2 Summit May 1, 2019 Last week scientists gathered at The Michael J. Fox Foundation (MJFF) office in New York to discuss progress toward slowing or stopping Parkinson's progression. Representatives from nine companies and 14 academic institutions attended our annual LRRK2 Summit to share advances and challenges that will inform future strategy around a leading Parkinson's drug target: LRRK2. Mutations in the gene that makes…
• Five Takeaways from Our LRRK2 Summit May 1, 2019 Last week scientists gathered at The Michael J. Fox Foundation (MJFF) office in New York to discuss progress toward slowing or stopping Parkinson's progression. Representatives from nine companies and 14 academic institutions attended our annual LRRK2 Summit to share advances and challenges that will inform future strategy around a leading Parkinson's drug target: LRRK2. Mutations in the gene that makes…