FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2967422457> ?p ?o ?g. }

• W2967422457 endingPage "3793" @default.
• W2967422457 startingPage "3782" @default.
• W2967422457 abstract "The hit-to-lead and lead optimization processes usually involve the design, synthesis, and profiling of thousands of analogs prior to clinical candidate nomination. A hit finding campaign may begin with a virtual screen that explores millions of compounds, if not more. However, this scale of computational profiling is not frequently performed in the hit-to-lead or lead optimization phases of drug discovery. This is likely due to the lack of appropriate computational tools to generate synthetically tractable lead-like compounds in silico, and a lack of computational methods to accurately profile compounds prospectively on a large scale. Recent advances in computational power and methods provide the ability to profile much larger libraries of ligands than previously possible. Herein, we report a new computational technique, referred to as “PathFinder”, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. In this work, the integration of PathFinder-driven compound generation, cloud-based FEP simulations, and active learning are used to rapidly optimize R-groups, and generate new cores for inhibitors of cyclin-dependent kinase 2 (CDK2). Using this approach, we explored >300 000 ideas, performed >5000 FEP simulations, and identified >100 ligands with a predicted IC50 < 100 nM, including four unique cores. To our knowledge, this is the largest set of FEP calculations disclosed in the literature to date. The rapid turnaround time, and scale of chemical exploration, suggests that this is a useful approach to accelerate the discovery of novel chemical matter in drug discovery campaigns." @default.
• W2967422457 created "2019-08-22" @default.
• W2967422457 creator A5004322104 @default.
• W2967422457 creator A5017942901 @default.
• W2967422457 creator A5019888088 @default.
• W2967422457 creator A5022991788 @default.
• W2967422457 creator A5036699127 @default.
• W2967422457 creator A5069375617 @default.
• W2967422457 creator A5071698522 @default.
• W2967422457 creator A5084246316 @default.
• W2967422457 creator A5088510099 @default.
• W2967422457 date "2019-08-12" @default.
• W2967422457 modified "2023-10-10" @default.
• W2967422457 title "Reaction-Based Enumeration, Active Learning, and Free Energy Calculations To Rapidly Explore Synthetically Tractable Chemical Space and Optimize Potency of Cyclin-Dependent Kinase 2 Inhibitors" @default.
• W2967422457 cites W1881469793 @default.
• W2967422457 cites W1965269139 @default.
• W2967422457 cites W1969487950 @default.
• W2967422457 cites W1975147762 @default.
• W2967422457 cites W1977620650 @default.
• W2967422457 cites W1985588649 @default.
• W2967422457 cites W1986240377 @default.
• W2967422457 cites W1997974358 @default.
• W2967422457 cites W1998848097 @default.
• W2967422457 cites W1999241626 @default.
• W2967422457 cites W2009423060 @default.
• W2967422457 cites W2009605433 @default.
• W2967422457 cites W2017254234 @default.
• W2967422457 cites W2031390939 @default.
• W2967422457 cites W2037825667 @default.
• W2967422457 cites W2039609876 @default.
• W2967422457 cites W2041686943 @default.
• W2967422457 cites W2046024621 @default.
• W2967422457 cites W2052933929 @default.
• W2967422457 cites W2056701057 @default.
• W2967422457 cites W2059126275 @default.
• W2967422457 cites W2060531713 @default.
• W2967422457 cites W2062458432 @default.
• W2967422457 cites W2064535969 @default.
• W2967422457 cites W2077804275 @default.
• W2967422457 cites W2117996566 @default.
• W2967422457 cites W2138778824 @default.
• W2967422457 cites W2141528038 @default.
• W2967422457 cites W2143419487 @default.
• W2967422457 cites W2146272590 @default.
• W2967422457 cites W2146984355 @default.
• W2967422457 cites W2166478947 @default.
• W2967422457 cites W2166550586 @default.
• W2967422457 cites W2204695023 @default.
• W2967422457 cites W2275489486 @default.
• W2967422457 cites W2310460235 @default.
• W2967422457 cites W2323942455 @default.
• W2967422457 cites W2324964582 @default.
• W2967422457 cites W2326892341 @default.
• W2967422457 cites W2330150548 @default.
• W2967422457 cites W2332896222 @default.
• W2967422457 cites W2413339906 @default.
• W2967422457 cites W2525356667 @default.
• W2967422457 cites W2564423501 @default.
• W2967422457 cites W2578240541 @default.
• W2967422457 cites W2580919858 @default.
• W2967422457 cites W2594183968 @default.
• W2967422457 cites W2610148085 @default.
• W2967422457 cites W2730519791 @default.
• W2967422457 cites W2736137960 @default.
• W2967422457 cites W2747592475 @default.
• W2967422457 cites W2765224015 @default.
• W2967422457 cites W2789615344 @default.
• W2967422457 cites W2790808809 @default.
• W2967422457 cites W2805201944 @default.
• W2967422457 cites W2912171584 @default.
• W2967422457 cites W2963445908 @default.
• W2967422457 cites W3098269892 @default.
• W2967422457 cites W4242320552 @default.
• W2967422457 cites W4248107770 @default.
• W2967422457 doi "https://doi.org/10.1021/acs.jcim.9b00367" @default.
• W2967422457 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31404495" @default.
• W2967422457 hasPublicationYear "2019" @default.
• W2967422457 type Work @default.
• W2967422457 sameAs 2967422457 @default.
• W2967422457 citedByCount "63" @default.
• W2967422457 countsByYear W29674224572019 @default.
• W2967422457 countsByYear W29674224572020 @default.
• W2967422457 countsByYear W29674224572021 @default.
• W2967422457 countsByYear W29674224572022 @default.
• W2967422457 countsByYear W29674224572023 @default.
• W2967422457 crossrefType "journal-article" @default.
• W2967422457 hasAuthorship W2967422457A5004322104 @default.
• W2967422457 hasAuthorship W2967422457A5017942901 @default.
• W2967422457 hasAuthorship W2967422457A5019888088 @default.
• W2967422457 hasAuthorship W2967422457A5022991788 @default.
• W2967422457 hasAuthorship W2967422457A5036699127 @default.
• W2967422457 hasAuthorship W2967422457A5069375617 @default.
• W2967422457 hasAuthorship W2967422457A5071698522 @default.
• W2967422457 hasAuthorship W2967422457A5084246316 @default.
• W2967422457 hasAuthorship W2967422457A5088510099 @default.
• W2967422457 hasBestOaLocation W29674224572 @default.
• W2967422457 hasConcept C103697762 @default.
• W2967422457 hasConcept C104317684 @default.

• next