Apicidin
Apicidin, a natural fugal metabolite, is a selective inhibitor of HDAC.
Histone deacetylases (HDAC) are enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. It has been revealed that histone acetyltransferase and histone deacetylase play important roles to either transcriptionally activate or repress gene expression through the reversible acetylation of lysine residues on a histone.
Apicidin has the potent and broad activity against apicomplexan parasites [1]. It has also been shown to have potent anti-angiogenesis activity and decrease HIF-1a levels in both human and mouse cancer cell lines [2].
The component has also been used extensively in vivo study to understand the role of HDAC in different physical processes. Apicidin exhibits anti-proliferative activity against different cancer cells lines in mice [3]. In a human colon HCT-116 carcinoma xenograft model, apicidin suppresses the tumor growth [4]. And it also exhibits the antitumor activity in a Ishikawa cell tumor xenograft model [5].
References:
1.Darkin-Rattray SJ, Gurnett AM, Myers RW, Dulski PM, Crumley TM, Allocco JJ, et al. Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase. Proc Natl Acad Sci U S A 1996,93:13143-13147.
2.Kim SH, Jeong JW, Park JA, Lee JW, Seo JH, Jung BK, et al. Regulation of the HIF-1alpha stability by histone deacetylases. Oncol Rep 2007,17:647-651.
3.Han JW, Ahn SH, Park SH, Wang SY, Bae GU, Seo DW, et al. Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin. Cancer Res 2000,60:6068-6074.
4.Jones P, Altamura S, De Francesco R, Paz OG, Kinzel O, Mesiti G, et al. A novel series of potent and selective ketone histone deacetylase inhibitors with antitumor activity in vivo. J Med Chem 2008,51:2350-2353.
5.Ahn MY, Chung HY, Choi WS, Lee BM, Yoon S, Kim HS. Anti-tumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4. Int J Oncol 2010,36:125-131.
- 1. Cheung CHY, Hsu CL, et al. "Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy." Cell Death Dis. 2019 Oct 17;10(11):786. PMID:31624245
- 2. Ballante F, Reddy DR, et al. "Structural insights of SmKDAC8 inhibitors: Targeting Schistosoma epigenetics through a combined structure-based 3D QSAR, in vitro and synthesis strategy." Bioorg Med Chem. 2017 Apr 1;25(7):2105-2132. PMID:28259528
- 3. Bagnall NH, Hines BM, et al. "Insecticidal activities of histone deacetylase inhibitors against a dipteran parasite of sheep, Lucilia cuprina." Int J Parasitol Drugs Drug Resist. 2017 Apr;7(1):51-60. PMID:28110187
| Physical Appearance | A crystalline solid |
| Storage | Store at -20°C |
| M.Wt | 623.78 |
| Cas No. | 183506-66-3 |
| Formula | C34H49N5O6 |
| Solubility | Limited solubility, soluble in DMSO or ethanol |
| Chemical Name | (3S,6S,9S,12R)-3-[(2S)-butan-2-yl]-6-[(1-methoxyindol-3-yl)methyl]-9-(6-oxooctyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone |
| SDF | Download SDF |
| Canonical SMILES | CCC(C)C1C(=O)N2CCCCC2C(=O)NC(C(=O)NC(C(=O)N1)CC3=CN(C4=CC=CC=C43)OC)CCCCCC(=O)CC |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
HeLa cells |
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Preparation method |
The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
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Reaction Conditions |
1 μg/mL; 24 hrs |
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Applications |
Apicidin exhibited long-lasting anti-proliferative activity against HeLa cells, up to 48 hrs after withdrawal. |
| Animal experiment [2]: | |
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Animal models |
Ishikawa endometrial cancer xenografted mouse model |
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Dosage form |
5 mg/kg; i.p.; q.d., for 21 days |
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Applications |
Significant inhibition of tumor growth was observed starting from day 15 after the Apicidin treatment. Apicidin (5 mg/kg) significantly inhibited tumor growth up to 53%. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Han JW, Ahn SH, Park SH, Wang SY, Bae GU, Seo DW, et al. Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin. Cancer Res 2000,60:6068-6074. [2]. Ahn MY, Chung HY, Choi WS, Lee BM, Yoon S, Kim HS. Anti-tumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4. Int J Oncol 2010,36:125-131. |
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| Description | Apicidin is an inhibitor of histone deacetylase (HDAC) with IC50 value 15.8 nM and 665.1 nM for HDAC3 and HDAC6, respectively. | |||||
| Targets | HDAC3 | HDAC6 | ||||
| IC50 | 15.8 nM | 665.1 nM | ||||
Quality Control & MSDS
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Chemical structure
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Related Biological Data
