Recent development of selective inhibitors targeting the HDAC6 as anti-cancer drugs: Structure, function and design.

HDAC6, a member of the histone deacetylase family, mainly is a cytosolic protein and regulates cell growth by acting on non-histone substrates, such as α -tubulin, cortactin, heat shock protein HSP90, programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), that are closely related to the proliferation, invasion, immune escape and angiogenesis of cancer tissues. The approved drugs targeting the HDACs are all pan-inhibitors and have many side effects due to their lack of selectivity. Therefore, development of selective inhibitors of HDAC6 has attracted much attention in the field of cancer therapy.

Design, synthesis, and biological evaluation of novel N-Benzyl piperidine derivatives as potent HDAC/AChE inhibitors for Alzheimer's disease.

The multitarget-directed ligands approach represents a potential strategy to provide effective treatments for Alzheimer's disease (AD) given its multifactorial pathology. Herein, a series of N-benzyl piperidine derivatives were designed, synthesized, and biologically characterized for dual inhibitions of histone deacetylase (HDAC) and acetylcholinesterase (AChE). Among the compounds tested, d5 and d10 exhibited dual enzyme inhibitions (d5: HDAC = 0.

Recent advances of small molecule JNK3 inhibitors for Alzheimer's disease.

C-Jun N-terminal kinase (JNK) is a member of mitogen-activated protein kinases (MAPKs) family, with three isoforms, JNK1, JNK2 and JNK3. Alzheimer's disease (AD) is a neurological disorder and the most common type of dementia. Two well-established AD pathologies are the deposition of Aβ amyloid plaques and neurofibrillary tangles caused by Tau hyperphosphorylation.