12772-57-5

Basic information

• Product Name: RADICICOL
• Synonyms: (1AR,2Z,4E,14R,15AR)-8-CHLORO-1A,14,15,15A-TETRAHYDRO-9,11-DIHYDROXY-14-METHYL-6H-OXIRENO[E][2]BENZOXACYCLOTETRADECIN-6,12(7H)-DIONE;[1AS-(1AR*,2Z,4E,14*,15AR*)]-8-CHLORO-1A,14,15,15A-TETRAHYDRO-9,11-DIHYDROXY-14-METHYL-6H-OXIRENO[E][2]BENZOXACYCLOTETRADECIN-6,12(7H)-DIONE;5-CHLORO-6-(7,8-EPOXY-10-HYDROXY-2-OXO-3,5-UNDECADIENYL)-BETA-RESORCYLIC ACID MU-LACTONE;FO-4910;KF58332;KF9-A;MONORDEN;MONORODENE
• CAS NO: 12772-57-5
• Molecular Formula: C₁₈H₁₇ClO₆
• Molecular Weight: 364.78
• Product Categories: Heat Shock Protein 90;antibiotic
• Mol File: 12772-57-5.mol
• Article Data: 7

Chemical Properties

• Melting Point: 193.5°
• Boiling Point: 656.2 °C at 760 mmHg
• Flash Point: 350.7 °C
• Appearance: yellow/solid
• Density: 1.364 g/cm³
• Vapor Pressure: 7.97E-18mmHg at 25°C
• Refractive Index: 1.583
• Storage Temp.: −20°C
• Solubility: ethanol: 10 mg/mL
• PKA: 6.29±0.40(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: RADICICOL(CAS DataBase Reference)
• NIST Chemistry Reference: RADICICOL(12772-57-5)
• EPA Substance Registry System: RADICICOL(12772-57-5)

Safety Data

• Hazard Codes: Xn,T
• Statements: 22-36/37/38-46-45
• Safety Statements: 26-45-53
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 1
• RTECS: RR1105000
• Hazardous Substances Data: 12772-57-5(Hazardous Substances Data)

Usage

Description

Radicicol (12772-57-5) inhibits heat shock protein 90 (HSP90) activity by binding to the ATP-binding pocket.1?In cells HSP90 client proteins such as Raf kinase2, HIF-1α3?and estrogen receptor4?are destabilized and proteolytically degraded. Radicicol inhibits expression of COX-2 without affecting COX-1 expression in LPS-stimulated macrophages (IC50=27 nM).5?Inhibits angiogenesis.6

Chemical Properties

Solid

Uses

Different sources of media describe the Uses of 12772-57-5 differently. You can refer to the following data:
1. Radicicol is a resorcylic acid lactone, produced by several fungal species, that exhibits broad spectrum antifungal and antitumour activity. Radicicol has been the subject of extensive investigation and inhibits protein tyrosine kinase, induces the differentiation of HL-60 cells into macrophages, blocks cell cycle at G1 and G2, suppresses NIH 3T3 cell transformation by diverse oncogenes such as src, ras and mos, and also suppresses the expression of mitogen-inducible cyclooxygenase-2. As a cell differentiation modulator, radicicol has anti-angiogenic activity in vivo, inhibiting the proliferation of plasminogen activator production by vascular endothelial cells.
2. Radicicol is an antitumor antibiotic, which inhibits the Hsp90 molecular chaperone.
3. Radicicol from Diheterospora chlamydosporia has been used as an inhibitor of heat shock protein 90 (Hsp90):to study its effects on lifespan extension and health in Caenorhabditis elegansto study its effects on protein aggregation in yeast to study its effects on xanthone sensitized cancer cells

Definition

ChEBI: An antifungal macrolactone antibiotic, obtained from Diheterospora chlamydosporia and Chaetomium chiversii that inhibits protein tyrosine kinase and heat shock protein 90 (Hsp90).

Biological Activity

Antifungal antibiotic. Inhibits heat shock protein 90 (Hsp90) activity by binding to the ATP-binding pocket, subsequently suppressing cell transformation induced by src, ras and mos. Represses estrogen receptor transcriptional activity and inhibits angiogenesis.

Biochem/physiol Actions

Radicicol is an antifungal macrolactone antibiotic that is found in Diheterospora chlamydosporia, Chaetomium chiversii, and Monosporium bonorden. It functions as an inhibitor of tyrosine kinase and heat shock protein 90 (Hsp90). Radicicol is involved in the suppression of transformation of various proto-oncogenes such as Ras, Mos, and Src. It also suppresses the activity of mitogen-induced cyclooxygenase-2 (COX-2) and phosphoinositide-dependent kinase 1 (PDK1). Radicicol is involved in arresting the cell cycle at the G1-S phase. It exhibits ant-cancer and anti-angiogenic activity in vivo.

References

1) Schulte?et al. (1999),?Interaction of radicicol with members of the heat shock protein 90 family of molecular chaperones; Mol. Endocrinol.,?13?1435 2) Soga?et al. (1998),?Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway; J. Biol. Chem.,?273?822 3) Hur?et al. (2002)?Reduction of hypoxia-induced transcription through the repression of hypoxia-inducible factor-1alpha/aryl hydrocarbon receptor nuclear translocator DNA binding by the 90-kDa heat-shock protein inhibitor radicicol; Mol. Pharmacol.,?62?975 4) Lee?et al.?(2002)?Radicicol represses the transcriptional function of the estrogen receptor by suppressing the stabilization of the receptor by heat shock protein 90; Mol. Cell. Endocrinol.,?188?47 5) Chanmugam et al. (1995)?Radicicol, a protein tyrosine kinase inhibitor, suppresses the expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide and in experimental glomerulonephritis; J. Biol. Chem.,?270?5418 6) Oikawa?et al. (1993)?Radicicol, a microbial cell differentiation modulator, inhibits in vivo angiogenesis; Eur. J. Pharmacol.,?241?221

InChI:InChI=1/C18H17ClO6/c1-9-6-15-14(25-15)5-3-2-4-10(20)7-11-16(18(23)24-9)12(21)8-13(22)17(11)19/h2-5,8-9,14-15,21-22H,6-7H2,1H3/b4-2+,5-3+/t9-,14-,15+/m1/s1

Upstream product

• 378749-99-6 ethyl (E,5S)-5-{[tert-butyl(diphenyl)silyl]oxy}-2-hexenoate 
• 378750-00-6 (2E,5S)-5-[(tert-butyldiphenylsilyl)oxy]hex-2-en-1-ol 
• 378749-97-4 2-(tert-Butyl-dimethyl-silanyloxy)-4-(tert-butyl-diphenyl-silanyloxy)-6-[((1E,3E)-2-penta-1,3-dienyl)-[1,3]dithian-2-ylmethyl]-benzoic acid (R)-1-methyl-2-((2R,3R)-3-vinyl-oxiranyl)-ethyl ester 
• 378749-98-5 C₄₃H₅₆O₅S₂Si₂ 
• 378749-96-3 4-(tert-Butyl-diphenyl-silanyloxy)-2-hydroxy-6-[((1E,3E)-2-penta-1,3-dienyl)-[1,3]dithian-2-ylmethyl]-benzoic acid (R)-1-methyl-2-((2R,3R)-3-vinyl-oxiranyl)-ethyl ester 
• 459144-99-1 6,8-Bis-(tert-butyl-dimethyl-silanyloxy)-3-[(E)-4-[(2S,3R)-3-((S)-2-hydroxy-propyl)-oxiranyl]-4-(4-methoxy-benzyloxy)-but-2-enyl]-isochromen-1-one 
• 459145-00-7 6-(tert-Butyl-dimethyl-silanyloxy)-8-hydroxy-3-[(E)-4-[(2S,3R)-3-((S)-2-hydroxy-propyl)-oxiranyl]-4-(4-methoxy-benzyloxy)-but-2-enyl]-isochromen-1-one 
• 140480-12-2 (9Z,11E)-(4R,6R,8R)-17,19-Bis-(tert-butyl-dimethyl-silanyloxy)-4-methyl-3,7-dioxa-tricyclo[13.4.0.0^6,8]nonadeca-1⁽¹⁵⁾,9,11,16,18-pentaene-2,13-dione 
• 140480-06-4 6,8-Bis-(tert-butyl-dimethyl-silanyloxy)-3-chloromethyl-isochromen-1-one 
• 867367-84-8 2,4-Bis-methoxymethoxy-6-(2-oxo-3-phenylsulfanyl-hex-5-enyl)-benzoic acid (R)-1-methyl-2-((2R,3R)-3-vinyl-oxiranyl)-ethyl ester 
• 754201-24-6 (Z)-(4R,6R,8R)-17,19-Bis-methoxymethoxy-4-methyl-12-phenylsulfanyl-3,7-dioxa-tricyclo[13.4.0.0^6,8]nonadeca-1⁽¹⁹⁾,9,15,17-tetraene-2,13-dione 
• 867367-98-4 2,4-Bis-methoxymethoxy-6-(2-oxo-3-phenylsulfanyl-hex-5-enyl)-benzoic acid (R)-1-methyl-2-((2R,3S)-3-vinyl-oxiranyl)-ethyl ester 
• 754201-23-5 (11Z,13E)-(7R,9R,10S)-1,10-Dichloro-9-hydroxy-2,4-bis-methoxymethoxy-7-methyl-7,8,9,10-tetrahydro-16H-6-oxa-benzocyclotetradecene-5,15-dione 
• 867367-85-9 2,4-Bis-methoxymethoxy-6-((E)-2-oxo-hexa-3,5-dienyl)-benzoic acid (R)-1-methyl-2-((2R,3R)-3-vinyl-oxiranyl)-ethyl ester 

Downstream Products

• 1178898-05-9 C₂₄H₂₃ClO₆S 
• 1178898-04-8 C₂₄H₂₃ClO₆S 
• 1178898-10-6 radicicol 10-(E)-O-benzyloxime 
• 1178898-09-3 radicicol 10-(Z)-O-benzyloxime 

Related news

Synthesis and structure–activity relationships of RADICICOL (cas 12772-57-5) derivatives and WNT-5A expression inhibitory activity09/04/2019

WNT-5A, a secretory glycoprotein, is related to the proliferation of dermal papilla cells. To develop a hair-growth stimulant, we have been searching for inhibitors of WNT-5A expression. We identified radicicol (1) as an active compound, and synthesized several radicicol derivatives. Among them,...detailed

Thermodynamics of RADICICOL (cas 12772-57-5) binding to human Hsp90 alpha and beta isoforms09/02/2019

Radicicol is a natural antibiotic that specifically inhibits chaperone Hsp90 activity and binds to its active site with nanomolar affinity. Radicicol has been widely used as a lead compound to generate synthetic analogs with reduced toxicity and increased stability that could be employed clinica...detailed

Radanamycin, a macrocyclic chimera of RADICICOL (cas 12772-57-5) and geldanamycin09/01/2019

Radicicol and geldanamycin are potent inhibitors of the Hsp90 protein folding machinery, which is an emerging target for the development of cancer chemotherapeutics. However, radicicol is inactive in vivo and geldanamycin suffers from its redox-active behavior that produces toxicity unrelated to...detailed

RADICICOL (cas 12772-57-5) improves regeneration of skeletal muscle previously damaged by crotoxin in mice08/31/2019

This work investigates the influence of heat shock proteins (HSPs) on necrosis and subsequent skeletal muscle regeneration induced by crotoxin (CTX), the major component of Crotalus durissus terrificus venom. Mice were treated with radicicol, a HSP inductor, followed by an intramuscular injectio...detailed

RADICICOL (cas 12772-57-5) induces intracellular accumulation of glycan-deficient clusterin variant08/29/2019

Proteostasis regulation using naturally occurring small molecules has been considered as a promising strategy for manipulating cancer sensitivity and therapy. Here, we identify a small molecule Hsp90 inhibitor radicicol that induces intracellular accumulation of cytotoxic clusterin variant. In t...detailed

RADICICOL (cas 12772-57-5) rescues yeast cell death triggered by expression of human α-synuclein and its A53T mutant, but not by human βA4 peptide and proapoptotic protein bax08/28/2019

Aggregation/misfolding of α-synuclein and βA4 proteins cause neuronal cell death (NCD) associated with Parkinson’s and Alzheimer’s disease. It has been suggested that a heat shock protein-90 (Hsp90) inhibitor can prevent NCD by activating the heat shock transcription factor-1 which, in turn,...detailed

Research ArticleTranscriptome analyses of the ginseng root rot pathogens Cylindrocarpon destructans and Fusarium solani to identify RADICICOL (cas 12772-57-5) resistance mechanisms08/27/2019

BackgroundThe ascomycete fungi Cylindrocarpon destructans (Cd) and Fusarium solani (Fs) cause ginseng root rot and significantly reduce the quality and yield of ginseng. Cd produces the secondary metabolite radicicol, which targets the molecular chaperone Hsp90. Fs is resistant to radicicol, whe...detailed

Relevant articles and documents

Convergent stereospecific total synthesis of monocillin I and radicicol: Some simplifications and improvements

A much improved and reliable access to the macrolide 9, key-intermediate in our synthesis of monocillin I and radicicol is reported, via a modification of our first synthesis. The formation of the conjugated E,Z-dienone trans-epoxide is now achieved in a much higher yield, in a stereospecific reaction, by elimination of the methanesulfonate ester of the 6′-OH of the intermediate macrolide. It is also shown that the configuration of the 6′-OH has no significant incidence on all the steps leading to 9, and that consequently the two diastereoisomers 12, epimeric at 6′, can be used for the synthesis of radicicol.

Synthesis and structure-activity relationships of radicicol derivatives and WNT-5A expression inhibitory activity

WNT-5A, a secretory glycoprotein, is related to the proliferation of dermal papilla cells. To develop a hair-growth stimulant, we have been searching for inhibitors of WNT-5A expression. We identified radicicol (1) as an active compound, and synthesized s

Modular asymmetric synthesis of pochonin C

Back to its origins: Pochonin C was synthesized in 11 steps from the four fragments shown in the scheme. This asymmetric synthesis and the conversion of pochonin C into radicicol defines the configuration at the center bearing the chlorine atom as S. lpc