KD5170, HDAC inhibitor

Supplementary info

This supplementary information is collated from multiple sources and compiled automatically.

Activity summary

HDACs (Histone Deacetylases) refer to a family of enzymes that includes HDAC1 HDAC2 HDAC3 HDAC4 HDAC5 HDAC6 HDAC7 HDAC9 HDAC10 and HDAC11. These proteins function mechanically by removing acetyl groups from lysine residues on histone proteins resulting in chromatin condensation and transcriptional repression. They exist in different mass forms typically around 50-70 kDa depending on the isoform. Expression of HDACs is found in various tissues throughout the body making them widespread in cellular processes.

Biological function summary

Histone deacetylases work to regulate gene expression by modulating chromatin structure. HDACs often function as part of larger multiprotein complexes such as the NuRD (Nucleosome Remodeling and Deacetylase) and the SIN3 complexes that coordinate chromatin modifications. Through their role in chromatin remodeling they influence critical biological processes like cell cycle progression and differentiation. HDAC inhibitors including compounds like 4-phenylbutyrate are investigated for their ability to reverse the effects of HDAC activity therefore impacting gene expression.

Pathways

Acetylation and deacetylation play important roles in regulating gene expression in pathways like the Notch and Hedgehog signaling pathways. HDACs interact with various proteins like the REST (RE1-Silencing Transcription Factor) to modulate neuronal gene expression. They often work in opposition to HATs (Histone Acetyltransferases) which add acetyl groups reflecting a balance critical for cellular function and development.

Associated diseases and disorders

HDACs are linked to cancer and neurodegenerative conditions like Alzheimer's disease. HDAC overexpression or dysfunction can lead to altered gene expression patterns that are characteristic of cancer pathways. In cancer HDACs interact with oncogenic transcription factors like c-Myc to drive cancer progression. Similarly in neurodegenerative diseases aberrant HDAC activity has been connected to dysfunctional neuronal gene regulation with connections to proteins involved in neurodegenerative disorders. HDAC inhibitors such as phenylbutyrate show promise in research as therapeutic agents to target these conditions by altering protein and gene functions.