Description
Santacruzamate A (1477949-42-0) is a highly potent and selective inhibitor of HDAC2 isolated from the Panamanian marine cyanobacteriumcf. Symploca(IC50=0.119 and 434 nM for HDAC2 and HDAC6 respectively).1Induces apoptosis and cancer cell death only in combination with other HDAC1 inhibitors.2Potential therapeutic agent for breast cancer.3Attenuates Aβ fragment (Aβ25-35)-induced toxicity in PC12 cells by enhancing ER stress tolerance.4Ameliorates Alzheimer’s disease-like pathology in mouse models.4
Uses
Santacruzamate A is a natural product isolated from Panamanian marine cyanobacterium Symploca sp; a histone deacetylases (HDACs) inhibitor; an attractive targeted therapy against breast cancer in women.
Definition
ChEBI: Santacruzamate A is an organooxygen compound and an organonitrogen compound. It is functionally related to a gamma-amino acid.
IC 50
HDAC2: 119 pM (IC
50); HDAC6: 434 nM (IC
50)
Background
Santacruzamate A is a cytotoxin isolated from the Panamanian marine cyanobacterium cf. Symploca sp., and is a highly selective inhibitor of histone deacetylases, specifically HDAC2 and HDAC6. This small molecule has been shown to induce apoptosis via transcriptional inhibition of HDAC2, resulting in an increase of p21 Waf1/Cip1 and p19INK4d expression when combined with an HDAC1 inhibitor. Santacruzamate A has also demonstrated the ability to attenuate amyloid-β protein fragment-induced toxicity through enhancing endoplasmic reticulum stress tolerance in mice. Additionally, HDAC2 has been recognized as a host immune response to the influenza A virus and several other viruses, making HDAC inhibitors important compounds to study in relation to viral diseases.
References
[1] CHRISTOPHER M. PAVLIK. Santacruzamate A, a Potent and Selective Histone Deacetylase Inhibitor from the Panamanian Marine Cyanobacterium cf. Symploca sp.[J]. Journal of Natural Products , 2013, 76 11: 2026-2033. DOI:
10.1021/np400198r[2] HENGYU ZHOU. Pharmacological or transcriptional inhibition of both HDAC1 and 2 leads to cell cycle blockage and apoptosis via p21Waf1/Cip1 and p19INK4d upregulation in hepatocellular carcinoma[J]. Cell Proliferation, 2018, 51 3. DOI:
10.1111/cpr.12447[3] C. DAMASKOS. Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer.[J]. Anticancer research, 2017, 37 1: 35-46. DOI:
10.21873/anticanres.11286[4] LEI CHEN. Santacruzamate A Ameliorates AD-Like Pathology by Enhancing ER Stress Tolerance Through Regulating the Functions of KDELR and Mia40-ALR in vivo and in vitro.[J]. ACS Applied Energy Materials, 2019: 61. DOI:
10.3389/fncel.2019.00061
