Modulating ADME Properties by Fluorination: MK2 Inhibitors with Improved Oral Exposure Article Swipe
Juraj Velcicky
,
Achim Schlapbach
,
Richard Heng
,
Láśzló Révész
,
Daniel Pflieger
,
Ernst Blum
,
Stuart Hawtin
,
Christine Huppertz
,
Roland Feifel
,
René Hersperger
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1021/acsmedchemlett.8b00098
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1021/acsmedchemlett.8b00098
MAP-activated protein kinase 2 (MK2) plays an important role in the regulation of innate immune response as well as in cell survival upon DNA damage. Despite its potential for the treatment of inflammation and cancer, to date no MK2 low molecular weight inhibitors have reached the clinic, mainly due to inadequate absorption, distribution, metabolism, and excretion (ADME) properties. We describe here an approach based on specifically placed fluorine within a recently described pyrrole-based MK2 inhibitor scaffold for manipulation of its physicochemical and ADME properties. While preserving target potency, the novel fluoro-derivatives showed greatly improved permeability as well as enhanced solubility and reduced in vivo clearance leading to significantly increased oral exposure.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1021/acsmedchemlett.8b00098
- OA Status
- green
- Cited By
- 19
- References
- 31
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2790645417
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W2790645417Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1021/acsmedchemlett.8b00098Digital Object Identifier
- Title
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Modulating ADME Properties by Fluorination: MK2 Inhibitors with Improved Oral ExposureWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2018Year of publication
- Publication date
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2018-03-20Full publication date if available
- Authors
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Juraj Velcicky, Achim Schlapbach, Richard Heng, Láśzló Révész, Daniel Pflieger, Ernst Blum, Stuart Hawtin, Christine Huppertz, Roland Feifel, René HerspergerList of authors in order
- Landing page
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https://doi.org/10.1021/acsmedchemlett.8b00098Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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greenOpen access status per OpenAlex
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https://doi.org/10.7270/q2vx0k5zDirect OA link when available
- Concepts
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ADME, Chemistry, In vivo, Pharmacology, Bioavailability, Kinase, In vitro, Biochemistry, Medicine, Biology, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
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19Total citation count in OpenAlex
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2024: 4, 2023: 2, 2022: 2, 2021: 5, 2020: 4Per-year citation counts (last 5 years)
- References (count)
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31Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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