Suberoylanilide hydroxamic acid SAHA

One of the first HDAC inhibitors to be identified and characterized was sodium butyrate, where it was found to alter the histone acetylation state (Riggs et al, 1977), and further determined to inhibit HDAC activity both in vitro and in vivo (Candido et al, 1978). Almost a decade later trichostatin A (TSA), a fungistatic antibiotic, was found to induce murine erythroleukemia cell differentiation (Yoshida et al, 1987). To date, a wide range of molecules have been described that inhibit the activity of Class I and Class II HDAC enzymes, and with a few exceptions, can be divided into structural classes including (1) small-molecule hydroxamates, such as TSA, suberoylanilide hydroxamic acid (SAHA), scriptaid and oxamflatin (2) short-chain fatty-acids, such as sodium butyrate, sodium phenylbutyrate and valproic acid (VPA) (3) cyclic tetrapeptides, such as apicidin, trapoxin and the depsipeptide FK-228 and (4) benzamides, such as MS-275 and Cl-994 (for reviews see Remiszewski et al, 2002 Miller et al, 2003). Some of these molecules are represented in Fig. 4. 

Suberoylanilide hydroxamic acid (SAHA) Class I/II Richon et al., 1998... 

HDAC inhibitors have received tremendous attention with the recent FDA approval of Vorinostat (Zolinza) or suberoylanilide hydroxamic acid (SAHA) for the treatment of cutaneous T-cell lymphoma (CTCL). Multiple compounds have thus entered into clinical trials for a wide variety of diseases. Many of these compounds were inspired in some part from HDAC natural product inhibitors. In addition, one natural product Romidepsin has also gained FDA approval for treating cutaneous T-cell lymphoma. 

Hydroxyamic acids Suberoylanilide hydroxamic acid (SAHA) Apoptosis, differentiation, and cell cycle arrest... 

Histone deacetylase (HDAC) inhibitors ameliorate a wide range of neurologic and psychiatric disorders in experimental models. Suberoylanilide hydroxamic acid (SAHA) was the first HDAC inhibitor approved by the FDA for the sole use of cancer therapy. SAHA also showed neurotrophic and neuroprotective effects in... 

Chen SH, Wu HM, Ossola B, Schendzielorz N, Wilson BC, Chu CH et al (2011) Suberoylanilide Hydroxamic Acid (SAHA), a histone deacetylase inhibitor, protects dopaminergic neurons from neurotoxin-induced damage. Br J Pharmacol 165 494-505... 

Trichostatin A (35) is structurally related to suberoylanilide hydroxamic acid (SAHA), a molecule that has reached the market as a therapy for the treatment of cutaneous T-cell lymphoma (CTCL), marketed as vorinostat. ° Hybrid derivatives have been synthesized combining features of trichostatin A and fungal-derived cyclic tetrapeptides such as trapoxin and apicidin, which show subnanomolar activities/ ... 

Zhou X, Yang XY, Popescu NC. Synergistic antineoplastic effect of DLCl tumor suppressor protein and histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), on prostate and hver cancer cells perspectives for therapeutics. Int J Oncol. 2019 36 999-1005. 

Almenara I, Rosato R, Grant S (2002) Synergistic induction of mitochondrial damage and apoptosis in human leukemia cells by flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Leukemia 16 1331-1343... 

Ruefli AA, Ausserlechner MJ, Bernhard D et al. (2001) The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species. Proc Natl Acad Sci U S A 98 10833-10838... 

HDACs represent a rational monotherapy or combination therapy for cancer treatment. Several HDAC inhibitors (HDACi s) are currently under clinical trials either as monotherapy or combination therapy agents against cancer [43]. The hydroxamate-containing HDACi s trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA, 13) exhibit the highest potency with excellent efficacy. 

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