1477949-42-0

Basic information

• Product Name: CAY10683 (SantacruzaMate A)
• Synonyms: CAY10683 (SantacruzaMate A);N-[4-oxo-4-[(2-phenylethyl)amino]butyl]-carbamic acid ethyl ester;Santacruzamate A (CAY10683);SantacruzaMate A;CAY10683;CAY1083;Carbamic acid, N-[4-oxo-4-[(2-phenylethyl)amino]butyl]-, ethyl ester
• CAS NO: 1477949-42-0
• Molecular Formula: C15H22N2O3
• Molecular Weight: 278.34678
• EINECS: -0
• Product Categories: Inhibitors
• Mol File: 1477949-42-0.mol

Chemical Properties

• Boiling Point: 508.1±43.0 °C(Predicted)
• Appearance: /
• Density: 1.087±0.06 g/cm3(Predicted)
• Storage Temp.: -20°
• Solubility: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 20 mg/ml).
• PKA: 12.68±0.46(Predicted)
• Stability: Stable for 2 years from date of purchse as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 2 months.
• CAS DataBase Reference: CAY10683 (SantacruzaMate A)(CAS DataBase Reference)
• NIST Chemistry Reference: CAY10683 (SantacruzaMate A)(1477949-42-0)
• EPA Substance Registry System: CAY10683 (SantacruzaMate A)(1477949-42-0)

Safety Data

• Hazardous Substances Data: 1477949-42-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
CAY10683 (SantacruzaMate A) is used as a targeted therapy agent for breast cancer in women due to its selective inhibition of HDAC2, which plays a role in the development and progression of the disease.
Used in Anticancer Applications:
CAY10683 (SantacruzaMate A) is used as an anticancer agent for breast cancer treatment, as it induces apoptosis and cancer cell death when combined with other HDAC1 inhibitors.
Used in Neurodegenerative Disease Research:
CAY10683 (SantacruzaMate A) is used as a potential therapeutic agent for Alzheimer's disease, as it has been shown to attenuate Aβ fragment-induced toxicity in PC12 cells and ameliorate Alzheimer's disease-like pathology in mouse models.
Used in Drug Delivery Systems:
While not explicitly mentioned in the provided materials, given the potential therapeutic applications of CAY10683 (SantacruzaMate A), it could be used in the development of novel drug delivery systems to enhance its bioavailability, delivery, and therapeutic outcomes in various medical applications.

References

1) Pavlik?et al.?(2013),?Santacruzamate A, a potent and selective histone deacetylase inhibitor from the Panamanian marine cyanobacterium cf. Symploca sp.; J. Nat. Prod.,?76?2026 2) Zhou?et al.?(2018),?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; Cell Prolif.,?51(3)?e12447 3) Damaskos?et al.?(2017),?Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer;?Anticancer Res.,?37?35 4) Chen?et al.?(2019),?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;?Front. Cell. Neurosci.,?13?61

Upstream product

• 4143-09-3 4-[(ethoxycarbonyl)amino]butanoic acid 
• 64-04-0 phenethylamine 

Relevant articles and documents

Synthesis and biological evaluation of Santacruzamate-A based analogues

Several derivatives of Santacruzamate-A, a natural product that is structurally related to SAHA, were synthesized to explore the potential of carbamates and oxalylamides as novel biasing element for targeting the catalytic site of zinc-dependent histone deacetylases (HDACs). An additional class of Santacruzamate-A derivatives was synthesized to investigate the influence of the cap group and the linker element on HDAC inhibitory activity. All compounds were evaluated in dose response for their in vitro cytotoxic activity in MTT assay in HCT116 cells. HDAC inhibitory activity was evaluated in vitro by western blot analysis for histone hyperacetylation assay and biochemically for representative human HDACs isoforms. Two novel compounds were identified to exhibit potent time dependent anti proliferative activity. However, unlike hydroxamic acid analogues, the tested Santacruzamate-A derivatives showed no noticeable HDAC inhibitory activity. The ethylcarbamate moiety as unusual zinc-binding group displayed no ability to coordinate the zinc ion and thus, presumably, was not able to reproduce known inhibitor-substrate zinc-binding group interactions with the HDAC catalytic site. This study confirmed that the accommodation of the zinc-binding group is deeply critical of the positioning of the linker and the projection of the cap group toward the different surface pockets of the enzyme.

Synthesis and biological evaluation of santacruzamate A and analogs as potential anticancer agents

Santacruzamate A, a recently discovered natural product from a Panamanian marine cyanobacterium Symploca sp., features a similar structure to the clinically used histone deacetylase (HDAC) inhibitor vorinostat (SAHA). We have synthesized the natural product and a small set of analogues for SAR studies. To our surprise, the synthetic natural product santacruzamate A (1a) and the analogues did not show an obvious inhibition even at 2 μM in HDAC enzyme assays while the IC50 value was 0.12 nM in the original report. However, a novel compound, 5, containing a terminal thiourea motif was found to inhibit the growth of malignant cells at submicromolar concentrations. Moreover, 5 was not cytotoxic to normal human colonic epithelial cells CCD841, suggesting that its cytotoxicity was specific to cancer cells. Further investigation indicated that the compound induced apoptosis, affected cell cycle progression and increased ROS production. We believe its mechanism of action is unrelated to HDAC inhibition and the original activity reported for santacruzamate needs to be reevaluated.

SANTACRUZAMATE A COMPOSITIONS AND ANALOGS AND METHODS OF USE

The compositions and methods described herein relate generally to Santacruzamate A compositions and analogs, which, among other features, are useful as histone deacetylase (HDAC) inhibitors.

Santacruzamate A, a potent and selective histone deacetylase inhibitor from the panamanian marine cyanobacterium cf. symploca sp.

A dark brown tuft-forming cyanobacterium, morphologically resembling the genus Symploca, was collected during an expedition to the Coiba National Park, a UNESCO World Heritage Site on the Pacific coast of Panama. Phylogenetic analysis of its 16S rRNA gene sequence indicated that it is 4.5% divergent from the type strain for Symploca and thus is likely a new genus. Fractionation of the crude extract led to the isolation of a new cytotoxin, designated santacruzamate A (1), which has several structural features in common with suberoylanilide hydroxamic acid [(2), SAHA, trade name Vorinostat], a clinically approved histone deacetylase (HDAC) inhibitor used to treat refractory cutaneous T-cell lymphoma. Recognition of the structural similarly of 1 and SAHA led to the characterization of santacruzamate A as a picomolar level selective inhibitor of HDAC2, a Class I HDAC, with relatively little inhibition of HDAC4 or HDAC6, both Class II HDACs. As a result, chemical syntheses of santacruzamate A as well as a structurally intriguing hybrid molecule, which blends aspects of both agents (1 and 2), were achieved and evaluated for their HDAC activity and specificity.