Histone deacetylases (HDACs) are a class of enzymes that remove acetyl groups from specific lysine residues on core histones, thereby regulating gene transcription via histone and chromatin structure modifications[2]. Santacruzamate A (CAY10683) is a picomolar level selective inhibitor of HDAC2, a Class I HDAC, with relatively little inhibition of HDAC4 or HDAC6, both Class II HDACs[3]. Pretreatment with Santacruzamate A resulted in a significant reduction in Aβ protein fragment 25–35 (Aβ25–35) -induced toxicity, with 2 µM STA showing the strongest protective effects in PC12, STA also rescues cognitive deficits in APPswe/PS1dE9 mice by enhancing ER stress tolerance[4]. Compared with the normal group, expression levels of inflammatory cytokine IL-1β and TNF-α were significantly increased in LPS activated BV2 microglial cells (P<0.05),CAY10683 could inhibit expression levels of inflammatory cytokine TNF-α and IL-1β in LPS activated BV2 microglial cells and LPS induced mice neuroinflammation[5]. CAY10683 improves histological and functional changes in ALF model. Compared with control group, LPS/D-GalN induced massive apoptosis of rat intestinal tissues and NCM460 cells (P<0.05), and the apoptosis rate was significantly reduced after CAY10683 treatment (P<0.05). The expression of Bax was increased significantly in the model groups (P<0.05), and reduced with the treatment of CAY10683 (P<0.05). Compared with the model group, CAY10683 inhibits mitochondrial apoptosis in intestinal tissues and NCM460 cells (P<0.05)[6].
To investigate the inhibitory effect of SCA on LPS-induced inflammatory response, the results showed that SCA significantly reduced the release of IL-1β, IL-6, and TNF-α.
ACS Pharmacol Transl Sci. 2024 Feb 16;7(4):1002-1012.
PC12 cells
10 µM
24 hours
To investigate the effect of SCA on the function of excitatory synaptic receptors in neuronal cells, the results showed that SCA significantly reduced the protein expression of GluN2A, GluN2B, GluA1, and GluA2.
ACS Pharmacol Transl Sci. 2024 Feb 16;7(4):1002-1012.
K562-R cells
0, 0.1, 0.25, 0.5 µM
48 hours
The combined treatment of CAY10683 and IM significantly increased the apoptotic rate of K562-R cells, showing a synergistic effect.
RSC Adv. 2020 Jan 3;10(2):828-844.
LAMA84-R cells
0, 0.1, 0.25, 0.5 µM
48 hours
The combined treatment of CAY10683 and IM significantly increased the apoptotic rate of LAMA84-R cells, showing a synergistic effect.
RSC Adv. 2020 Jan 3;10(2):828-844.
MDA-MB-231
25 µM
5 days
Santacruzamate A inhibited the nuclear translocation of PD-L1, thereby reducing the production of NCS-induced pro-inflammatory cytokines.
EMBO Rep. 2025 Feb;26(3):635-655.
HuT-78 cutaneous T-cell lymphoma cells
1.4 µM
72 hours
To test the cytotoxicity of Santacruzamate A on HuT-78 cells, the results showed a GI50 value of 1.4 µM.
Symploca sp. J Nat Prod.
Human dermal fibroblast cells (hDF)
>100 µM
72 hours
To test the cytotoxicity of Santacruzamate A on human dermal fibroblast cells, the results showed a GI50 value greater than 100 µM.
Symploca sp. J Nat Prod.
MCF-7
23.7 µM
72 hours
Inhibited cell proliferation
Bioorg Med Chem. 2016 Nov 1;24(21):5183-5196.
MCF-7
13.8 µM
72 hours
Inhibited cell proliferation
Bioorg Med Chem. 2016 Nov 1;24(21):5183-5196.
HCT116
17.2 µM
72 hours
Inhibited cell proliferation
Bioorg Med Chem. 2016 Nov 1;24(21):5183-5196.
HCT-116 colon cancer cells
29.4 µM
96 hours
To test the cytotoxicity of Santacruzamate A on HCT-116 cells, the results showed a GI50 value of 29.4 µM.
Symploca sp. J Nat Prod.
Santacruzamate A 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
Complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain model
Intragastric administration
2, 10, 50 mg/kg
Once daily for 3 days
To investigate the effect of SCA on CFA-induced chronic inflammatory pain and related anxiety and depressive-like behaviors, the results showed that SCA significantly alleviated pain, anxiety, and depressive-like behaviors, and inhibited microglial activation in the ACC region.
ACS Pharmacol Transl Sci. 2024 Feb 16;7(4):1002-1012.
BALB/c-Nude mice
Colorectal cancer xenograft model
Intraperitoneal injection
5 mg/kg
Daily for 12 days
SCA combined with 5-FU or regorafenib significantly inhibited tumor growth and activated NLRP3-mediated pyroptosis.
Clin Transl Med. 2024 Jun;14(6):e1692.
NOD/SCID mice
K562-R xenograft model
Intraperitoneal injection
50 mg/kg
Once daily for 21 days
The combined treatment of CAY10683 and IM significantly suppressed the proliferation of K562-R cells in vivo, showing a synergistic effect.
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