p(FPLX:HDAC)

Entity

Name

HDAC

Namespace

FPLX

Namespace Version

20180917

Namespace URL

https://raw.githubusercontent.com/sorgerlab/famplex/e8ae9926ff95266032cb74f77973c84939bffbeb/export/famplex.belns

Tau Modifications Sections of NESTOR

Although low-level tau acetylation was observed in untreated HEK-T40 cells, treatment with the pan histone deacetylase (HDAC) inhibitor trichostatin A (TSA), but not the Sir2 class inhibitor nicotinamide, resulted in a dramatic increase in acetylated tau levels. PubMed:21427723

Modification of the cap group of biphenylacrylohydroxamic acid-based HDAC inhibitors led to the identification of a new derivative (3) characterized by an indolyl-substituted 4-phenylcinnamic skeleton. PubMed:26890116

In conclusion, ST7612AA1, prodrug of ST7464AA1, is the first of a new generation of HDAC inhibitors, very potent, orally administered, and well tolerated. It is a thiol derivative, pan-histone deacetylase inhibitor, active against a broad panel of cancer cell lines and in vivo tumor models. PubMed:27917100

Treatment with Givinostat (1.2 µM) lead to a nearly 7-fold increase in the fraction of ThS + cells (from ~ 12% to ~ 84%, Fig. S4A and B, blue lines) compared to the uninduced control, and 2.5-fold compared to the induced control. PubMed:30640040

Tab. 1A-B: Summary of the Tau aggregation modulators (inhibitors = 18 (A), stimulators = 10 (B)) which show decrease / increase in the amount of ThS + cells without affecting the expression level of TauRD∆K compared to the compound untreated control. PubMed:30640040

Although low-level tau acetylation was observed in untreated HEK-T40 cells, treatment with the pan histone deacetylase (HDAC) inhibitor trichostatin A (TSA), but not the Sir2 class inhibitor nicotinamide, resulted in a dramatic increase in acetylated tau levels. PubMed:21427723

Conversely, compounds related to HDAC inhibition (16 of 20) led to enhanced Tau aggregation, suggesting that HDAC activity is important for suppressing aggregation PubMed:30640040

Tab. 1A-B: Summary of the Tau aggregation modulators (inhibitors = 18 (A), stimulators = 10 (B)) which show decrease / increase in the amount of ThS + cells without affecting the expression level of TauRD∆K compared to the compound untreated control. PubMed:30640040