Matches in SemOpenAlex for { <https://semopenalex.org/work/W2078826114> ?p ?o ?g. }
Showing items 1 to 53 of
53
with 100 items per page.
- W2078826114 abstract "Neuroinflammation as a component of CNS disease is a complex process that involves a diversity of changes in products produced by glia. One change is the increased production of proinflammatory cytokines in response to diverse stressors. Clinical observations and preclinical animal studies identify increased cytokine production as a potential contributor to disease progression, requiring that it be tested as a potential drug discovery target for CNS disorders such as Alzheimer's disease (AD). Because restoration of homeostasis is the goal, candidate therapies must be selective in their action (i.e., NOT pan-suppressors of glia function). Current FDA-approved drugs that modulate cytokine function are macromolecules, which have disadvantages for chronic CNS disorders. Therefore, there is a critical unmet need for small molecule, orally active, brain-penetrant compounds that can reduce excessive proinflammatory cytokine production by glia back towards basal levels with resultant improvement in neurologic outcomes. To address this need, we are using a de novo synthetic chemistry platform integrated with hierarchal biology screening to develop candidate compounds that attenuate excessive proinflammatory cytokine production and modify disease progression in animal models. We refer to the approach as use of “smart chemistry” integrated with “smart biology”. An inactive core scaffold was subjected to focused chemical diversification based on chemoinformatics and pharmacoinformatics to generative novel compounds that were prioritized based on screening their promise for metabolic stability, oral bioavailability, brain uptake, and lack of toxicity. Qualified compounds were subjected to efficacy testing in animal models. Novel candidate compounds emerged within an accelerated timeline and limited budget. The unbiased, function-driven approach yielded one group of analogs referred to as the Minozac family, whereas the single molecular target approach that was focused on a protein kinase candidate yielded the Minokine family of compounds. Both Minozac and Minokine are efficacious in an AD-relevant animal model. The integrative approach, being increasingly adopted in academia and industry, allows for rapid and efficient discovery of novel small molecules that are candidates for therapeutic development campaigns focused on modification of disease progression." @default.
- W2078826114 created "2016-06-24" @default.
- W2078826114 creator A5024523607 @default.
- W2078826114 date "2008-07-01" @default.
- W2078826114 modified "2023-10-16" @default.
- W2078826114 title "S4-02-06: Integrative approach targeting neuroinflammation" @default.
- W2078826114 doi "https://doi.org/10.1016/j.jalz.2008.05.484" @default.
- W2078826114 hasPublicationYear "2008" @default.
- W2078826114 type Work @default.
- W2078826114 sameAs 2078826114 @default.
- W2078826114 citedByCount "0" @default.
- W2078826114 crossrefType "journal-article" @default.
- W2078826114 hasAuthorship W2078826114A5024523607 @default.
- W2078826114 hasBestOaLocation W20788261141 @default.
- W2078826114 hasConcept C164027704 @default.
- W2078826114 hasConcept C169760540 @default.
- W2078826114 hasConcept C203014093 @default.
- W2078826114 hasConcept C2776914184 @default.
- W2078826114 hasConcept C60644358 @default.
- W2078826114 hasConcept C71924100 @default.
- W2078826114 hasConcept C74187038 @default.
- W2078826114 hasConcept C86803240 @default.
- W2078826114 hasConcept C87753298 @default.
- W2078826114 hasConcept C98274493 @default.
- W2078826114 hasConceptScore W2078826114C164027704 @default.
- W2078826114 hasConceptScore W2078826114C169760540 @default.
- W2078826114 hasConceptScore W2078826114C203014093 @default.
- W2078826114 hasConceptScore W2078826114C2776914184 @default.
- W2078826114 hasConceptScore W2078826114C60644358 @default.
- W2078826114 hasConceptScore W2078826114C71924100 @default.
- W2078826114 hasConceptScore W2078826114C74187038 @default.
- W2078826114 hasConceptScore W2078826114C86803240 @default.
- W2078826114 hasConceptScore W2078826114C87753298 @default.
- W2078826114 hasConceptScore W2078826114C98274493 @default.
- W2078826114 hasIssue "4S_Part_5" @default.
- W2078826114 hasLocation W20788261141 @default.
- W2078826114 hasOpenAccess W2078826114 @default.
- W2078826114 hasPrimaryLocation W20788261141 @default.
- W2078826114 hasRelatedWork W1979761312 @default.
- W2078826114 hasRelatedWork W1989357518 @default.
- W2078826114 hasRelatedWork W2053418060 @default.
- W2078826114 hasRelatedWork W2748566357 @default.
- W2078826114 hasRelatedWork W2772533035 @default.
- W2078826114 hasRelatedWork W3036788916 @default.
- W2078826114 hasRelatedWork W3186266400 @default.
- W2078826114 hasRelatedWork W4225146093 @default.
- W2078826114 hasRelatedWork W4226282915 @default.
- W2078826114 hasRelatedWork W4386476278 @default.
- W2078826114 hasVolume "4" @default.
- W2078826114 isParatext "false" @default.
- W2078826114 isRetracted "false" @default.
- W2078826114 magId "2078826114" @default.
- W2078826114 workType "article" @default.