Santacruzamate A (CAY10683)
(Synonyms: HDAC抑制剂,CAY-10683) 目录号 : GC14439
Santacruzamate A (CAY10683)是一种天然氨基甲酸酯衍生物，可抑制HDAC2和HDAC6活性，IC50值分别为0.119nM和434nM。
Cas No.:1477949-42-0
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Santacruzamate A (CAY10683), a natural carbamate derivative, inhibits HDAC2 and HDAC6 with IC50 values of 0.119 and 434nM, respectively [1]. Santacruzamate A exhibits immunomodulatory and cell proliferation inhibitory activities and modulates the synaptic function in neurons by inhibiting microglial activation[2]. Santacruzamate A has been widely used in the development of a series of related derivatives aimed at inhibiting HDAC isoenzymes[3].
In vitro, Santacruzamate A treatment for 24 hours significantly inhibited the viability of NCM460 cells, with an IC50 value of 315.7nM[4]. Santacruzamate A treatment at 50µM for 6 hours inhibited the invasion and migration of NUCKS1-overexpressing colorectal cancer (CRC) cells, reduced the expression of HDAC2 protein without affecting the expression of NUCKS1 protein[5]. Treatment with 10µM Santacruzamate A for 24 hours significantly inhibited the cell viability of BV2 microglial cells, suppressed the expression of HDAC2 and increased the acetylation level of histone H3, accompanied by a decrease in the expression of IL-1β and TNF-α[6].
In vivo, Santacruzamate, administered via intraperitoneal injection (2mg/kg every other day) for 6 weeks, resulted in an increase in the expression of GLT-1, p-GluN2B and p-GluA1 in the hippocampal tissue of the mouse model of subarachnoid hemorrhage (SAH), alleviating the depressive symptoms of the SAH mice[7]. Intravenous injection of Santacruzamate A (3mg/kg) every three days for 35 days inhibited the distant metastasis of the tumor in the xenograft mouse model of SW620 cells[8].
References:
[1] Pavlik C M, Wong C Y B, Ononye S, et al. 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.
[2] Zhou H, Cai Y, Liu D, et al. Pharmacological or transcriptional inhibition of both HDAC 1 and 2 leads to cell cycle blockage and apoptosis via p21Waf1/Cip1 and p19INK4d upregulation in hepatocellular carcinoma[J]. Cell proliferation, 2018, 51(3): e12447.
[3] Randino R, Gazzerro P, Mazitschek R, et al. Synthesis and biological evaluation of Santacruzamate-A based analogues[J]. Bioorganic & Medicinal Chemistry, 2017, 25(24): 6486-6491.
[4] Wang Y, Chen H, Chen Q, et al. The protective mechanism of CAY10683 on intestinal mucosal barrier in acute liver failure through LPS/TLR4/MyD88 pathway[J]. Mediators of Inflammation, 2018, 2018(1): 7859601.
[5]Zhu L, Zhao T, Su H, et al. NUCKS1 promotes invasion and metastasis of colorectal cancer by stabilizing HDAC2 and activating AKT[J]. Oncogenesis, 2025, 14(1): 19.
[6] Jiao F Z, Wang Y, Zhang H Y, et al. Histone deacetylase 2 inhibitor CAY10683 alleviates lipopolysaccharide induced neuroinflammation through attenuating TLR4/NF-κB signaling pathway[J]. Neurochemical research, 2018, 43(6): 1161-1170.
[7] Tao K, Cai Q, Zhang X, et al. Astrocytic histone deacetylase 2 facilitates delayed depression and memory impairment after subarachnoid hemorrhage by negatively regulating glutamate transporter-1[J]. Annals of Translational Medicine, 2020, 8(11): 691.
[8] Zheng Y, Dai M, Dong Y, et al. ZEB2/TWIST1/PRMT5/NuRD multicomplex contributes to the epigenetic regulation of EMT and metastasis in colorectal carcinoma[J]. Cancers, 2022, 14(14): 3426.
Santacruzamate A (CAY10683)是一种天然氨基甲酸酯衍生物，可抑制HDAC2和HDAC6活性，IC50值分别为0.119nM和434nM[1]。Santacruzamate A具有免疫调节和细胞增殖抑制活性，并通过抑制小胶质细胞活化调节神经元突触功能[2]。Santacruzamate A已被广泛作为先导化合物用于开发靶向HDAC同工酶的系列衍生物[3]。
在体外，Santacruzamate A处理24小时可显著抑制NCM460细胞活力，IC50值为315.7nM[4]。50µM的Santacruzamate A处理6小时能抑制NUCKS1过表达结直肠癌（CRC）细胞的侵袭和迁移，降低HDAC2蛋白表达且不影响NUCKS1蛋白水平[5]。10µM的Santacruzamate A处理BV2小胶质细胞24小时可显著抑制细胞活力，下调HDAC2表达并提高组蛋白H3乙酰化水平，同时降低IL-1β和TNF-α表达[6]。
在体内，蛛网膜下腔出血（SAH）小鼠模型隔日腹腔注射Santacruzamate A（2mg/kg；持续6周）可增加海马组织中GLT-1、p-GluN2B和p-GluA1表达，缓解小鼠抑郁症状[7]。SW620细胞异种移植瘤小鼠模型每三天静脉注射3mg/kg剂量的Santacruzamate A（持续35天）能抑制肿瘤远处转移[8]。
| Cell experiment [1]: | |
Cell lines | BV2 microglial cells |
Preparation Method | BV2 microglial cells were cultured in DMEM medium supplemented with heat-inactivated 10% fetal bovine serum and 100U penicillin/100g streptomycin. The cells were grown in a humidified incubator at 37°C with 95% air and 5% CO2. The cells (1×104 cells per well) were seeded in 96-well microtiter plates and treated with Santacruzamate A (0.01, 0.1, 1, 10 and 100µM) for 24 hours. Then, 10µL of CCK-8 dye was added to each well and the plates were incubated at 37°C for 2 hours. The absorbance of each well was measured at 450nm wavelength. |
Reaction Conditions | 0.01, 0.1, 1, 10 and 100µM; 24h |
Applications | Santacruzamate A treatment significantly inhibited viability of BV2 microglial cells ≥10µM. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | Eighty-six adult C57BL/6 mice (body weight: 20.0-25.0g) were housed under a temperature of 25.0 ± 3.0°C and with a 12:12 light-dark cycle. Anesthesia with 2% isoflurane was administered to mice. A midline incision was made in the neck to expose the left carotid bifurcation. The external carotid artery was ligated and separated, and a 6-0 sharp-ended monofilament was inserted into the internal carotid artery. The monofilament was inserted 10-12mm to the bifurcation of the anterior cerebral artery and the middle cerebral artery, and then 3mm further inward for puncture. The line was left in place for 20 seconds to establish the intravascular perforation model of subarachnoid hemorrhage (SAH) in mice. Two weeks after the surgery, SAH mice were intraperitoneally injected with Santacruzamate A (2mg/kg) every other day for 6 weeks. The expressions of GLT-1, HDAC2, p-GluN2B and p-GluA1 in the hippocampal tissue of mice were detected. |
Dosage form | 2mg/kg every other day for 6 weeks; i.p. |
Applications | Santacruzamate A treatment led to an increase in the expression of GLT-1, p-GluN2B and p-GluA1 in the hippocampal tissue of mice, and the expression of HDAC2 decreased. |
References: | |
| Cas No. | 1477949-42-0 | SDF | |
| 别名 | HDAC抑制剂,CAY-10683 | ||
| 化学名 | ethyl N-[4-oxo-4-(2-phenylethylamino)butyl]carbamate | ||
| Canonical SMILES | CCOC(=O)NCCCC(=O)NCCC1=CC=CC=C1 | ||
| 分子式 | C15H22N2O3 | 分子量 | 278.35 |
| 溶解度 | ≥ 8.8mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.5926 mL | 17.963 mL | 35.926 mL |
| 5 mM | 718.5 μL | 3.5926 mL | 7.1852 mL |
| 10 mM | 359.3 μL | 1.7963 mL | 3.5926 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet