12772-57-5 Usage
Description
Radicicol, with the chemical formula (12772-57-5), is a resorcylic acid lactone antibiotic derived from various fungal species, such as Diheterospora chlamydosporia and Chaetomium chiversii. It is a solid compound that exhibits broad-spectrum antifungal and antitumor activities. Radicicol functions as an inhibitor of heat shock protein 90 (Hsp90) by binding to its ATP-binding pocket, leading to the destabilization and proteolytic degradation of HSP90 client proteins. Additionally, it inhibits the expression of mitogen-inducible cyclooxygenase-2 (COX-2) without affecting COX-1 expression in LPS-stimulated macrophages and possesses anti-angiogenic properties.
Uses
Used in Anticancer Applications:
RADICICOL is used as an antitumor agent for inhibiting the Hsp90 molecular chaperone, which plays a crucial role in the stabilization and activation of various client proteins involved in cancer progression.
Used in Cellular and Molecular Research:
RADICICOL is used as an inhibitor of heat shock protein 90 (Hsp90) to study its effects on lifespan extension and health in Caenorhabditis elegans, protein aggregation in yeast, and the sensitization of xanthone-treated cancer cells.
Used in Pharmaceutical Industry:
RADICICOL is used as a cell differentiation modulator for its anti-angiogenic activity in vivo, inhibiting the proliferation of plasminogen activator production by vascular endothelial cells. This property makes it a valuable compound for the development of novel drug delivery systems and therapeutic strategies against cancer.
Used in Fungal Infection Treatment:
RADICICOL is used as a broad-spectrum antifungal agent for its ability to inhibit protein tyrosine kinase, block cell cycle at G1 and G2 phases, and suppress the transformation of NIH 3T3 cells by diverse oncogenes such as src, ras, and mos.
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
Check Digit Verification of cas no
The CAS Registry Mumber 12772-57-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,2,7,7 and 2 respectively; the second part has 2 digits, 5 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 12772-57:
(7*1)+(6*2)+(5*7)+(4*7)+(3*2)+(2*5)+(1*7)=105
105 % 10 = 5
So 12772-57-5 is a valid CAS Registry Number.
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
12772-57-5Relevant articles and documents
Convergent stereospecific total synthesis of monocillin I and radicicol: Some simplifications and improvements
Tichkowsky, Isabelle,Lett, Robert
, p. 3997 - 4001 (2002)
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
Shinonaga, Hideki,Noguchi, Toshiya,Ikeda, Akiko,Aoki, Mari,Fujimoto, Natsuko,Kawashima, Akira
body text, p. 4622 - 4635 (2009/10/23)
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
Barluenga, Sofia,Lopez, Pilar,Moulin, Emilie,Winssinger, Nicolas
, p. 3467 - 3470 (2007/10/03)
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