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ALX-380-092 Revised 03-Jul-08
Radicicol
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SYNONYMS Monorden
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
PRODUCT LINE Natural Products / Antibiotics
PRODUCT CATEGORY Antibiotics - Antifungal
Ordering Information
Product Numbers: Format: Size: Unit Price: Quantity: Add To Cart
ALX-380-092-M001   1 mg 75.00 USD Add To Cart
ALX-380-092-M005   5 mg 295.00 USD Add To Cart
Product Specification
FORMULA: C18H17ClO6
MW: 364.8
CAS NUMBER: 12772-57-5
MERCK INDEX: 14: 6253
RTECS: RR1105000
SOURCE/HOST: Isolated from Humicola fuscoatra.
PURITY: ≥98% (HPLC)
APPEARANCE: White to light yellow powder.
SOLUBILITY: Soluble in DMSO, methanol or acetone.
SHIPPING: AMBIENT
LONG TERM STORAGE: -20°C
HANDLING: Protect from light.
HAZARD: MAY BE CARCINOGENIC. HARMFUL.

Product Description
Antifungal macrocyclic lactone antibiotic with antimalarial activity. Potent inhibitor of HSP90. Binds more strongly to HSP90 (nanomolar affinity) than to Grp94. Also binds to yeast HSP90, E. coli HtpG and TRAP-1. Non-competitive inhibitor of ATP citrate lyase. Anti-angiogenic. Specifically inhibits the interaction between HIF-1α/Arnt heterodimer and the hypoxia-responsive element (HRE), reducing VEGF expression. Protein tyrosine kinase inhibitor, e.g. p60v-src (IC50=0.27nM). Inhibitor of cyclooxygenase-2 (COX-2) expression (IC50=27nM) without affecting COX-1 expression in LPS-stimulated macrophages. Induces the differentiation of HL-60 cells into macrophages, blocking cell cycle at G1 and G2. Suppressor of NIH 3T3 cell transformation by diverse oncogenes such as mos, ras and src in part by blocking the key signal transduction intermediates such as MAP kinase and GAP-associated p62. Inhibitor of AP-1-, NF-κB- and serum response factor (SRF)-mediated transcription (e.g. expression of iNOS). Represses the transcriptional function of the estrogen receptor. Inhibits archeal growth and DNA topoisomerase VI (a Topo IIB family topoisomerase). Blocks replication of negative-strand RNA viruses.
Product Specific Literature References
Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol: H.J. Kwon, et al.; Cancer Res. 52, 6926 (1992) Abstract
Radicicol, a microbial cell differentiation modulator, inhibits in vivo angiogenesis: T. Oikawa, et al.; Eur. J. Pharmacol. 241, 221 (1993) Abstract
Radicicol, a protein tyrosine kinase inhibitor, suppresses the expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide and in experimental glomerulonephritis: P. Chanmugam, et al.; J. Biol. Chem. 270, 5418 (1995) Abstract; Full Text
Suppression of RAS and MOS transformation by radicicol: J.F. Zhao, et al.; Oncogene 11, 161 (1995) Abstract
Induction of differentiation of HL-60 cells by the anti-fungal antibiotic, radicicol: Y. Shimada, et al.; J. Antibiot. 48, 824 (1995) Abstract
Radicicol inhibits tyrosine phosphorylation of the mitotic Src substrate Sam68 and retards subsequent exit from mitosis of Src-transformed cells: I. Pillay, et al.; Cell Growth Differ. 7, 1487 (1996) Abstract
Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway: S. Soga, et al.; J. Biol. Chem. 273, 822 (1998) Abstract; Full Text
Antimalarial activity of radicicol, heptelidic acid and other fungal metabolites: Y. Tanaka, et al.; J. Antibiot. 51, 153 (1998) Abstract
Targeting of the protein chaperone, HSP90, by the transformation suppressing agent, radicicol: S.V. Sharma, et al.; Oncogene 16, 2369 (1998) Abstract
Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin: S.M. Roe, et al.; J. Med. Chem. 42, 260 (1999) Abstract
T.W. Schulte, et al.; Mol. Endocrinol. 13, 1435 (1999) Abstract; Full Text
Radicicol suppresses expression of inducible nitric-oxide synthase by blocking p38 kinase and nuclear factor-kappaB/Rel in lipopolysaccharide-stimulated macrophages: Y.J. Jeon, et al.; J. Pharmacol. Exp. Ther. 294, 548 (2000) Abstract; Full Text
Radicicol binds and inhibits mammalian ATP citrate lyase: S.W. Ki, et al.; J. Biol. Chem. 275, 39231 (2000) Abstract; Full Text
Radicicol suppresses transformation and restores tropomyosin-2 expression in both ras- and MEK-transformed cells without inhibiting the Raf/MEK/ERK signaling cascade: P.N. Kim, et al.; Cell Growth Differ. 12, 543 (2001) Abstract; Full Text
Radicicol-sensitive peptide binding to the N-terminal portion of GRP94: S. Vogen, et al.; J. Biol. Chem. 277, 40742 (2002) Abstract; Full Text
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: E. Hur, et al.; Mol. Pharmacol. 62, 975 (2002) Abstract; Full Text
Radicicol represses the transcriptional function of the estrogen receptor by suppressing the stabilization of the receptor by heat shock protein 90: M.O. Lee, et al.; Mol. Cell Endocrinol. 188, 47 (2002) Abstract
Development of radicicol analogues: S. Soga, et al.; Curr. Cancer Drug Targets 3, 359 (2003) Abstract
Heat shock protein 90 (Hsp90) chaperone complex inhibitor, radicicol, potentiated radiation-induced cell killing in a hormone-sensitive prostate cancer cell line through degradation of the androgen receptor: K. Harashima, et al.; Int. J. Radiat. Biol. 81, 63 (2005) Abstract
Inhibition of archaeal growth and DNA topoisomerase VI activities by the Hsp90 inhibitor radicicol: D. Gadelle, et al.; Nucleic Acid Res. 33, 2310 (2005) Abstract
Geldanamycin, radicicol, and chimeric inhibitors of the Hsp90 N-terminal ATP binding site: M.K. Hadden, et al.; Curr. Top. Med. Chem. 6, 1173 (2006), Review Abstract
The topoisomerase II-Hsp90 complex: a new chemotherapeutic target?: C.R. Barker, et al.; Int. J. Cancer 118, 2685 (2006) Abstract
Structural basis for topoisomerase VI inhibition by the anti-Hsp90 drug radicicol: K.D. Corbett & J.M. Berger; Nucleic Acids Res. 34, 4269 (2006) Abstract
Chemistry and biology of resorcylic acid lactones: N. Winssinger & S. Barluenga; Chem. Commun. (Camb.) 22 (2007) Abstract
Antiviral activity and RNA polymerase degradation following Hsp90 inhibition in a range of negative strand viruses: J.H. Connor, et al.; Virology 362, 109 (2007) Abstract
 
 

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