183506-66-3

Basic information

• Product Name: APICIDIN
• Synonyms: APICIDIN, FUSARIUM SPECIES;Ccris 9163;Apicidin Ia;Cyclo(8-oxo-L-2-aMinodecanoyl-1-Methoxy-L-tryptophyl-L-isoleucyl- D-2-piperidinecarbonyl);Cyclo[(2S)-2-aMino-8-oxodecanoyl-1-Methoxy-L-tryptophyl-L-isoleucyl-(2R)-2-piperidinecarbonyl];OSI 2040;Apicidin Cyclo[(2S)-2-amino-8-oxodecanoyl-1-methoxy-L-tryptophyl-L-isoleucyl-(2R)-2-piperidinecarbonyl];CYCLO-L-(2-AMINO-8-OXODEACANOYL)-L-(N-METHOXY-TRYPTOPHAN)-L-ISOLEUCYL-D-PIPECOLINYL
• CAS NO: 183506-66-3
• Molecular Formula: C₃₄H₄₉N₅O₆
• Molecular Weight: 609.76
• Product Categories: antibiotic
• Mol File: 183506-66-3.mol
• Article Data: 1

Chemical Properties

• Appearance: /solid
• Density: 1.27g/cm³
• Refractive Index: 1.615
• Storage Temp.: −20°C
• Solubility: DMSO: ~1mg/mL
• PKA: 13.09±0.70(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months. Compound is prone to oxidation. Protect from exposure to air.
• CAS DataBase Reference: APICIDIN(CAS DataBase Reference)
• NIST Chemistry Reference: APICIDIN(183506-66-3)
• EPA Substance Registry System: APICIDIN(183506-66-3)

Safety Data

• Hazard Codes: T+
• Statements: 26/27/28
• Safety Statements: 22-26-36/37/39-45
• RIDADR: UN 2811 6.1/PG 2
• WGK Germany: 3
• Hazardous Substances Data: 183506-66-3(Hazardous Substances Data)

Usage

Description

Apicidin is a cyclic tetrapeptide fungal metabolite that functions as a potent, cell permeable inhibitor of histone deacetylases (HDACs). It possesses antitumor properties by inducing changes in p21WAF1/Cip1 and gelsolin gene expression, leading to cell cycle arrest in the G1 phase. Additionally, it dramatically decreases HIF-1α protein levels and transcriptional activity in human and mouse tumor cell lines. Apicidin also exhibits antiprotozoal and potential antimalarial properties, as well as anti-angiogenic and apoptosis-inducing effects.

Uses

Used in Pharmaceutical Industry:
Apicidin is used as a histone deacetylase inhibitor for its antitumor properties, inducing changes in gene expression and causing cell cycle arrest in the G1 phase. This makes it a promising candidate for the development of anticancer therapies.
Used in Antimalarial Applications:
Apicidin is used for its potential antimalarial properties, offering a new avenue for the treatment of malaria.
Used in Antiparasitic Applications:
Apicidin is used as a broad-spectrum antiparasitic and antiprotozoan agent, providing a means to combat various parasitic infections.
Used in Research:
Apicidin is used as a histone deacetylase 2 (HDAC2) inhibitor to study its effects on 5-lipoxygenase (5-LO) mRNA expression in cell lines of Mono Mac6. It is also used to investigate the effects of toll-like receptor 8 (TLR-8) stimulation and histone modification on the expression of an activator protein 1 [AP-1] family member (Fra-2) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in monocytes.
Used in Anti-angiogenic and Apoptosis-inducing Applications:
Apicidin is used for its anti-angiogenic properties, which can help inhibit the formation of new blood vessels in tumors, and its ability to induce apoptosis, leading to the programmed cell death of cancerous cells.

Biochem/physiol Actions

Apicidin is a potent inhibitor of histone deacetylase (HDAC). It particularlyinhibits histone deacetylase 1 and 3 (HDAC1 and HDAC3). Apicidin exhibits anti-protozoal activity against apicomplexan metabolite produced by parasites. It also possesses anti-proliferative activity against several cancer cell lines. Apicidin shows anti-cancer activity against human acute promyelocytic leukemia cell.

Enzyme inhibitor

This fungal metabolite and potential oral chemotherapeutic agent (FW = 623.79 g/mol; CAS 183506-66-3), also known as [cyclo(N-O-methyl-L- tryptophanyl-L-isoleucinyl-D-pipecolinyl-L-2-amino-8-oxodecanoyl)], is an antiprotozoal agent. It is cell permeable and is a strong inhibitor of histone deacetylase (IC50 = 0.7 nM). Apicidin also inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin. Apicidin’s low bioavailability of apicidin is mainly due to the P-gycoprotein-mediated efflux.

References

1) Darkin-Rattray,?et al. (1996)?Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase; Proc. Nat. Acad. Sci. USA,?93?13143 2) Han?et al. (2000)?Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin; Cancer Res.,?60?6068 3) Kim?et al. (2007)?Regulation of the HIF-1alpha stability by histone deacetylases; Oncol. Rep.?17?647

InChI:InChI=1/C34H49N5O6/c1-5-22(3)30-34(44)38-19-13-12-18-29(38)33(43)35-26(16-9-7-8-14-24(40)6-2)31(41)36-27(32(42)37-30)20-23-21-39(45-4)28-17-11-10-15-25(23)28/h10-11,15,17,21-22,26-27,29-30H,5-9,12-14,16,18-20H2,1-4H3,(H,35,43)(H,36,41)(H,37,42)/t22-,26-,27-,29+,30-/m0/s1

Upstream product

• 330814-50-1 (5-bromo-1-ethyl-pentyloxy)-tert-butyl-diphenyl-silane 
• 330814-54-5 1-{2-[2-[2-tert-butoxycarbonylamino-8-(tert-butyl-diphenyl-silanyloxy)-decanoylamino]-3-(1-methoxy-1H-indol-3-yl)-propionylamino]-3-methyl-pentanoyl}-piperidine-2-carboxylic acid methyl ester 
• 330814-52-3 2-[2-tert-butoxycarbonylamino-8-(tert-butyl-diphenyl-silanyloxy)-decanoylamino]-3-(1-methoxy-1H-indol-3-yl)-propionic acid 
• 330814-51-2 2-tert-butoxycarbonylamino-8-(tert-butyl-diphenyl-silanyloxy)-decanoic acid 
• 147960-24-5 methyl (((9H-fluoren-9-yl)methoxy)carbonyl)-L-tryptophanate 
• 330814-49-8 2-amino-3-(1-methoxy-1H-indol-3-yl)-propionic acid methyl ester 
• 35677-83-9 (+)-2R-Piperidine-2-carboxylic acid methyl ester 
• 87184-80-3 5-tert-butyldimethylsilyloxypentanal 
• 83067-20-3 5-(tert-butyldimethyl-silyloxy)pentan-1-ol 
• 13139-16-7 N-(tert-butyloxycarbonyl)-L-isoleucine 
• 111-29-5 1 ,5-pentanediol 
• 314058-15-6 (6S,9S,12S,14aR)-6-((S)-sec-Butyl)-12-(6-hydroxy-octyl)-9-(1-methoxy-1H-indol-3-ylmethyl)-decahydro-4a,7,10,13-tetraaza-benzocyclododecene-5,8,11,14-tetraone 

Downstream Products

• 375858-14-3 (2S)-2-amino-8-oxodecanoic acid 
• 73-32-5 L-isoleucine 
• 1723-00-8 (R)-(+)-pipecolic acid 
• 73-22-3 L-Tryptophan 
• 183506-67-4 Apicidin A 

Relevant articles and documents

Synthesis of apicidin

Tetrapeptide containing L-2-amino-8-protected hydroxydecanoic acid, L-N-O-methyltryptophan, L-isoleucine and D-pipecolinic acid was cyclized with pentafluorophenyl diphenylphosphinate. The cyclic tetrapeptide was deprotected and oxidized to apicidin [cyclo-(N-O-methyl-L-Trp-L-Ile-D-Pip-L-2-amino-8-oxo-decanoyl)].