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1d was driven by bioisosteric replacement of the fragments bound to subpockets A-C, scaffold-hopping, de novo design, and medicinal chemistry and was facilitated by SZMAP/GamePlan 37 , vBrood 38 , and MOE software 39

C., Fahling, M., Schiebel, H., Thiele, B

Depletion of CBP is directly linked with cellular toxicity caused by mutant huntingtin

Key mechanisms: Directly inhibits NF-B the central transcription factor governing the body's inflammatory cascade Suppresses MAP kinase signalling pathways Reduces pro-inflammatory cytokines including TNF-, IL-1, and IL-6 Acts via PepT1 transporters in intestinal epithelial and immune cells, targeting gut-resident inflammation at the tissue level The evidence: A landmark study published in Gastroenterology demonstrated that nanomolar concentrations of KPV inhibit NF-B and MAP kinase inflammatory pathways and reduce pro-inflammatory cytokine secretion and that oral administration of KPV reduces the incidence of chemically induced colitis in mice as measured by both histology and cytokine expression