VORINOSTAT
new epigenetic drug
- Created by: ava.scott
- Created on: 12-04-18 10:57
View mindmap
- VORINOSTAT
- WHAT?
- A histone deacetylase (HDAC) inhibitor
- molecular weight
- 264
- Treats cutaneous T cell lymphoma
- CTCL
- ref
- Bubna 2015
- HOW DOES IT DO IT?
- Transcriptional activity
- causes acetylation of Bcl-6, a TF
- inhibits the represseing effect of Bcl-6
- this would presumably work on expressing tumor suppressor genes
- inhibits the represseing effect of Bcl-6
- acetylation of lysine residues
- such as alpha tubulin
- such as heat-shock protein 90
- decreases pro-growth activity and pro-survival clients
- such as Brc-abl
- such as c-raf
- such as AKT in human leukemia
- causes acetylation of Bcl-6, a TF
- Non-transcriptional
- cell cycle arrest
- upregulates cyclin-independent kinase inhibtor p 21
- antagonises cyclin-CDK complexes
- causes G1 cycle arrest
- antagonises cyclin-CDK complexes
- upregulates cyclin-independent kinase inhibtor p 21
- apoptosis
- changes balance of pro and anti-apoptosis enzymes
- enhances external signals for cell death
- down regulates cell survival proteins such as
- BCL-1 and BCL-2
- THESE REGULATE MITOCHONDRIAL ACTIVITY
- BCL-1 and BCL-2
- vorinostat stabilises p53 which is important in CTCL lines
- inhibits angiogenesis
- induces hypoxia-inducible factor (HIF) and blocks angiogenesis.
- cell cycle arrest
- Inhibits class I and II HDAC enzymes
- causes acetylated proteins to accumulate, such as histones
- we dont know:
- how it is selective for tumor cells
- the presence of thioredoxin in normla cells may buffer the drugs effect
- Untitled
- how it is selective for tumor cells
- Transcriptional activity
- WHAT?
Comments
No comments have yet been made