AI Article Synopsis
- * This new inhibitor shows significant improvements in inhibition levels compared to an earlier compound, with up to 2.8-fold better performance across various PI3K isoforms.
- * In mouse models, the inhibitor demonstrated better tumor-killing abilities and oral bioavailability, making it a promising option for treating melanoma.
Article Abstract
The structure-based design of a new single entity, MEK/PI3K bifunctional inhibitor (, ), which displays improved MEK1 and PI3K isoform inhibition, is described. demonstrated a 2.2-fold improvement in MEK1 inhibition and a 2.8-, 2.7-, 23-, and 2.5-fold improved inhibition toward the PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ isoforms, respectively, as compared to a previous lead compound (; ) in enzymatic inhibition assays. demonstrated superior tumoricidal efficacy over in an A375 melanoma spheroid tumor model. was comparatively more effective than in promoting tumor control when administrated orally in a tumor therapy study conducted in an A375 melanoma mouse model confirming its bioavailability and efficacy toward combined MEK1/PI3K inhibition.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554897 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.7b00111 | DOI Listing |
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