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 (183506-66-3) is a fungal toxin that is a potent, cell permeable inhibitor of histone deacetylases (HDAC’s).1?It also displays antitumor properties by inducing changes in p21WAF1/Cip1 and gelsolin gene expression causing cell cycle arrest in the G1?phase.2?Apicidin dramatically decreases HIF-1α protein levels and transcriptional activity in human and mouse tumor cell lines.3

Chemical Properties

Solid

Uses

Different sources of media describe the Uses of 183506-66-3 differently. You can refer to the following data:
1. Apicidin is a potent (nM) cell permeable inhibitor of histone deacetylase. Also, Apicidin exhibits antiprotozoal and potential antimalarial properties. Apicidin has antiproliferative activity on HeLa cells accompanied by cell arrest at the G1 phase. Apicidin induces selective changes in the expression of p21 and gelsolin.
2. Apicidin is a cyclic peptide antibiotic with broad spectrum antiparasitic and antiprotozoan activity. Apicidin, a histone deacetylase inhibitor, is anti-angiogenic and induces apoptosis.
3. Apicidin has been 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 has also been used to study 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.

General Description

Apicidin is a cyclic tetrapeptide fungal metabolite.

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

• 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 
• 111-29-5 1 ,5-pentanediol 
• 13139-16-7 N-(tert-butyloxycarbonyl)-L-isoleucine 
• 83067-20-3 5-(tert-butyldimethyl-silyloxy)pentan-1-ol 
• 87184-80-3 5-tert-butyldimethylsilyloxypentanal 
• 35677-83-9 (+)-2R-Piperidine-2-carboxylic acid methyl ester 
• 330814-49-8 2-amino-3-(1-methoxy-1H-indol-3-yl)-propionic acid methyl ester 
• 330814-50-1 (5-bromo-1-ethyl-pentyloxy)-tert-butyl-diphenyl-silane 
• 147960-24-5 methyl (((9H-fluoren-9-yl)methoxy)carbonyl)-L-tryptophanate 
• 330814-51-2 2-tert-butoxycarbonylamino-8-(tert-butyl-diphenyl-silanyloxy)-decanoic acid 
• 330814-52-3 2-[2-tert-butoxycarbonylamino-8-(tert-butyl-diphenyl-silanyloxy)-decanoylamino]-3-(1-methoxy-1H-indol-3-yl)-propionic acid 
• 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 

Downstream Products

• 183506-67-4 Apicidin A 
• 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 

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)].