ALEXIS Biochemicals: UCN-02

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ALX-380-054

Revised 18-Jun-08

Geldanamycin
PRODUCT LINE	Natural Products / Antibiotics
PRODUCT CATEGORY	Antibiotics - Protein Kinase Inhibitors

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-380-054-C100		100 µg	28.00 USD
ALX-380-054-C500		500 µg	50.00 USD
ALX-380-054-M001		1 mg	75.00 USD
ALX-380-054-M005		5 mg	300.00 USD

Product Specification

FORMULA:	C₂₉H₄₀N₂O₉
MW:	560.6
CAS NUMBER:	30562-34-6
RTECS:	LX8920000
SOURCE/HOST:	Isolated from Streptomyces hygroscopicus.
PURITY:	≥96%
APPEARANCE:	Yellow solid.
SOLUBILITY:	Slightly soluble in methanol, chloroform or DMSO; insoluble in water.
SHIPPING:	AMBIENT
LONG TERM STORAGE:	-20°C
HANDLING:	Protect from light.

Product Description

Potent antitumor antibiotic. Inhibitor of pp60^src tyrosine kinase and of c-myc gene expression in murine lymphoblastoma cells. Inhibits the transforming activity of abl, erbB, fps, src, and yes. Binds specifically to heat shock protein 90 (HSP90) and to its endoplasmic reticulum homolog GP96 (GRP94). Capable of destabilizing several oncogene and proto-oncogene products. Potent inhibitor of the nuclear hormone receptor family. Protects against α-synuclein toxicity to dopaminergic neurons in Drosophila. Destabilizes mutant p53 protein from a number of breast, leukemic, and prostate cell lines. Inhibits basal and hypoxia-induced expression of c-Jun (IC₅₀=75nM) and abolishes hypoxia-induced increase in c-Jun N-terminal kinase (JNK) activity. Inhibits telomerase activity through inhibition of HSP90, a chaperone required for the assembly and activation of telomerase in human cells. ~10-fold more potent than herbimycin A (Prod. No. ALX-350-029)

Product Specific Literature References

Geldanamycin, a new antibiotic: C. DeBoer, et al.; J. Antibiot. 23, 442 (1970) Abstract
Phenotypic change from transformed to normal induced by benzoquinonoid ansamycins accompanies inactivation of p60src in rat kidney cells infected with Rous sarcoma virus: Y. Uehara, et al.; Mol. Cell. Biol. 6, 2198 (1986) Abstract
Inhibition of c-myc gene expression in murine lymphoblastoma cells by geldanamycin and herbimycin, antibiotics of benzoquinoid ansamycin group: H. Yamaki, et al.; J.Antibiot. 42, 604 (1989) Abstract
Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation: L. Whitesell, et al.; PNAS 91, 8324 (1994) Abstract
Geldanamycin selectively destabilizes and conformationally alters mutated p53: M.V. Blagosklonny, et al.; Oncogene 11, 933 (1995) Abstract
Inhibition of the oncogene product p185erbB-2 in vitro and in vivo by geldanamycin and dihydrogeldanamycin derivatives: R.C. Schnur, et al.; J. Med. Chem. 38, 3806 (1995) Abstract
p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2: C. Chavany, et al.; J. Biol. Chem. 271, 4974 (1996) Abstract; Full Text
Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells: L. Whitesell & P. Cook; Mol. Endocrinol. 10, 705 (1996) Abstract
Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity: L. Neckers, et al.; Invest. New Drugs 17, 361 (1999), (Review) Abstract
Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs: M.V. Blagosklonny; Leukemia 16, 455 (2002), (Review) Abstract
Pharmacological prevention of Parkinson disease in Drosophila: P.K. Auluck & N.M. Bonini; Nat. Med. 8, 1185 (2002) Abstract
Effects of geldanamycin on signaling through activator-protein 1 in hypoxic HT29 human colon adenocarcinoma cells: I.A. Vasilevskaya and P.J. O'Dwyer; Cancer Res. 59, 3935 (1999) Abstract
Inhibition of telomerase activity by geldanamycin and 17-allylamino, 17-demethoxygeldanamycin in human melanoma cells: R. Villa, et al.; Carcinogenesis 24, 851 (2003) Abstract
Chaperoning oncogenes: HSP90 as a target of geldanamycin: L. Neckers; Handb. Exp. Pharmacol. 259 (2006), (Review) Abstract
Geldanamycin interferes with the 90-kDa heat shock protein, affecting lipopolysaccharide-mediated interleukin-1 expression and apoptosis within macrophages: H.Y. Hsu, et al.; Mol. Pharmacol. 71, 344 (2007) Abstract; Full Text
Relationship among ligand conformations in solution, in the solid state, and at the Hsp90 binding site: geldanamycin and radicicol: P. Thepchatri, et al.; JACS 129, 3127 (2007) Abstract
Inhibition of heat shock protein 90 impairs epidermal growth factor-mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivo: S.A. Lang, et al.; Mol. Cancer Ther. 6, 1123 (2007) Abstract; Full Text
Geldanamycin, a heat-shock protein 90-binding agent, induces thymocyte apoptosis through destabilization of Lck in presence of 12-O-tetradecanoylphorbol 13-acetate: K. Ohta, et al.; Biomed. Res. 28, 33 (2007) Abstract; Full Text
Low dose geldanamycin inhibits hepatocyte growth factor and hypoxia-stimulated invasion of cancer cells: F. Koga, et al.; Cell Cycle 6, 1393 (2007) Abstract
The heat-shock protein 90 inhibitor, geldanamycin, induces apoptotic cell death in Epstein-Barr virus-positive NK/T-cell lymphoma by Akt down-regulation: Y.K. Jeon, et al.; J. Pathol. 213, 170 (2007) Abstract
Geldanamycin, a HSP90 inhibitor, attenuates the hypoxia-induced vascular endothelial growth factor expression in retinal pigment epithelium cells in vitro: W.C. Wu, et al.; Exp. Eye Res. 85, 721 (2007) Abstract
HSP90 antagonist, geldanamycin, inhibits proliferation, induces apoptosis and blocks migration of rhabdomyosarcoma cells in vitro and seeding into bone marrow in vivo: E. Lesko, et al.; Anticancer Drugs 18, 1173 (2007) Abstract
Geldanamycin enhances hepatocyte growth factor stimulation of eNOS phosphorylation in endothelial cells: K. Makondo, et al.; Eur. J. Pharmacol. 582, 110 (2007) Abstract
Hsp90-inhibitor geldanamycin abrogates G(2) arrest in p53-negative leukemia cell lines through the depletion of Chk1: K. Sugimoto, et al.; Oncogene 27, 3091 (2008) Abstract

Further Categories Containing This Product:

Tyrosine Kinase Inhibitors • Chaperone-mediated Autophagy [CMA] • Antitumor Antibiotics • HSP90/HtpG/Related Products • Antitumor Agents (DNA Interaction & Gene Regulation)

ALX-350-029

Revised 05-Apr-08

Herbimycin A
PRODUCT LINE	Natural Products / Antibiotics
PRODUCT CATEGORY	Antibiotics - Protein Kinase Inhibitors

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-350-029-C100		100 µg	110.00 USD
ALX-350-029-M001		1 mg	560.00 USD

Product Specification

FORMULA:	C₃₀H₄₂N₂O₉
MW:	574.7
CAS NUMBER:	70563-58-5
RTECS:	LX8930000
SOURCE/HOST:	Isolated from Streptomyces sp.
PURITY:	≥97%
APPEARANCE:	Yellow powder.
SOLUBILITY:	Soluble in DMSO.
SHIPPING:	AMBIENT
LONG TERM STORAGE:	+4°C
HANDLING:	Protect from light.
HAZARD:	NEUROTOXIN.

Product Description

Antibiotic. Cell permeable tyrosine kinase inhibitor. Inhibitor of HSP90, NF-κB activation and angiogenesis. Increases the sensitivity of certain cancer cells to chemotherapeutic agents. Blocks mitotic activity.

Product Specific Literature References

Herbimycin, a new antibiotic produced by a strain of Streptomyces: S. Omura, et al.; J. Antibiot. (Tokyo) 32, 255 (1979) Abstract
A new activity of herbimycin A: inhibition of angiogenesis: T. Yamashita, et al.; J. Antibiot. (Tokyo) 42, 1015 (1989) Abstract
Stimulation by Bt2cAMP of epidermal mucous metaplasia in retinol- pretreated chick embryonic cultured skin, and its inhibition by herbimycin A, an inhibitor for protein-tyrosine kinase: A. Obinata, et al.; Exp. Cell. Res. 193, 36 (1991) Abstract
IgE-induced tyrosine phosphorylation of phospholipase C-gamma 1 in rat basophilic leukemia cells: D.J. Park, et al.; J. Biol. Chem. 266, 24237 (1991) Abstract; Full Text
Bacterial lipopolysaccharide stimulates protein tyrosine phosphorylation in macrophages: S.L. Weinstein, et al.; PNAS 88, 4148 (1991) Abstract
Inhibition of interleukin 3 and granulocyte-macrophage colony- stimulating factor stimulated increase of active ras.GTP by herbimycin A, a specific inhibitor of tyrosine kinases: T. Satoh, et al.; J. Biol. Chem. 267, 2537 (1992) Abstract; Full Text
New insight into oncoprotein-targeted antitumor effect: herbimycin A as an antagonist of protein tyrosine kinase against Ph1-positive leukemia cells: M. Okabe and M. Uehara; Leuk. Lymphoma 12, 41 (1993) Abstract
Prevention of anti-CD3 monoclonal antibody-induced thymic apoptosis by protein tyrosine kinase inhibitors: K. Migita, et al.; J. Immunol. 153, 3457 (1994) Abstract
Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation: L. Whitesell, et al.; PNAS 91, 8324 (1994) Abstract; Full Text
Inhibition of PDGF-induced phospholipase D but not phospholipase C activation by herbimycin A: B.Y. Kim; BBRC 212, 1061 (1995) Abstract
Controlling the vasculature: angiogenesis, anti-angiogenesis and vascular targeting of gene therapy: T.-P.D. Fan, et al.; TIPS 16, 57 (1995), (Review) Abstract
Herbimycin A enhances apoptotic effect of chemotherapeutic drugs on K562 cells: H. Ren, et al.; Chin. Med. J. (Engl.) 111, 678 (1998) Abstract
Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs: M.V. Blagosklonny; Leukemia 16, 455 (2002) Abstract; Full Text
Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells’ sensitivity to cytotoxic drugs: D.T. Jones, et al.; Blood 103, 1855 (2004) Abstract; Full Text
Herbimycin A abrogates nuclear factor-kappaB activation by interacting preferentially with the IkappaB kinase beta subunit: S. Ogino, et al.; Mol. Pharmacol. 65, 1344 (2004) Abstract; Full Text
Herbimycin A suppresses mitotic activity and egg production of female Schistosoma mansoni: J. Knobloch, et al.; Int. J. Parasitol. 36, 1261 (2006) Abstract

Further Categories Containing This Product:

Tyrosine Kinase Inhibitors • Phospholipase D/Related Products • Neurotoxins • Antibiotics for Angiogenesis Research • HSP90/HtpG/Related Products

ALX-380-116

Revised 07-Apr-08

Hypothemycin
PRODUCT LINE	Natural Products / Antibiotics
PRODUCT CATEGORY	Antibiotics - Antifungal

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-380-116-C250		250 µg	140.00 USD
ALX-380-116-M001		1 mg	420.00 USD

Product Specification

FORMULA:	C₁₉H₂₂O₈
MW:	378.4
CAS NUMBER:	76958-67-3
SOURCE/HOST:	Isolated from Phoma sp.
PURITY:	≥98% (HPLC)
APPEARANCE:	Off-white solid.
SOLUBILITY:	Soluble in DMSO or acetone; insoluble in methanol or water.
SHIPPING:	AMBIENT
LONG TERM STORAGE:	-20°C

Product Description

Exhibits antifungal and cytotoxic activity against some tumor cell lines partly attributed to inhibition of Ras-inducible genes. Inhibits proliferation of mouse and human T cells and modulates production of cytokines during T cell activation. Facilitates the ubiquitinylation process of cyclin D1. Has been identified as a potent and selective inhibitor of threonine/tyrosine-specific kinase, MEK, and other protein kinases that contain a conserved cysteine residue in the ATP-binding site in both in vitro and in vivo studies.

Product Specific Literature References

Metabolites of pyrenomycetes XIII: Structure of (+) hypothemycin, an antibiotic macrolide from hypomyces trichothecoides: M.S.R. Nair & S.T. Carey; Tetrahedron Lett. 21, 2011 (1980)
Metabolites of pyrenomycetes. XIV: Structure and partial stereochemistry of the antibiotic macrolides hypothemycin and dihydrohypothemycin: M.S.R. Nair, et al.; Tetrahedron 37, 2445 (1981)
Revised structure and stereochemistry of hypothemycin: T. Agatsuma et al.; Chem. Pharm. Bull. 41, 373 (1993)
Antitumor efficacy of hypothemycin, a new Ras-signaling inhibitor: H. Tanaka, et al.; Jpn. J. Cancer Res. 90, 1139 (1999) Abstract
Hypothemycin inhibits the proliferative response and modulates the production of cytokines during T cell activation: R. Camacho, et al.; Immunopharmacology 44, 255 (1999) Abstract
Suppression of oncogenic transformation by hypothemycin associated with accelerated cyclin D1 degradation through ubiquitin-proteasome pathway: H. Sonoda, et al.; Life Sci. 65, 381 (1999) Abstract
Resorcylic acid lactones: naturally occurring potent and selective inhibitors of MEK: A. Zhao, et al.; J. Antibiot. 52, 1086 (1999) Abstract
Targeted covalent inactivation of protein kinases by resorcylic acid lactone polyketides: A. Schirmer, et al.; PNAS 103, 4234 (2006) Abstract; Full Text
Chemistry and biology of resorcylic acid lactones: N. Winssinger, et al.; Chem. Commun. (Camb). 1, 22 (2007), (Review) Abstract

Further Categories Containing This Product:

MAPK Pathway Inhibitors • Antibiotics - Protein Kinase Inhibitors • CDKs & Cyclins Other Products • Tyrosine Kinase Inhibitors • Antitumor Agents (DNA Interaction & Gene Regulation) • Antitumor Antibiotics • Ras Signalling Pathway Other Products • Antibiotics - Proteasome/Ubiquitin Modulators • Ubiquitination Other Products

ALX-380-267

Revised 11-Feb-08

LL-Z1640-2
PRODUCT LINE	Natural Products / Antibiotics
PRODUCT CATEGORY	Antibiotics - Protein Kinase Inhibitors

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-380-267-M001		1 mg	50.00 USD
ALX-380-267-M005		5 mg	200.00 USD

Product Specification

FORMULA:	C₁₉H₂₂O₇
MW:	362.4
CAS NUMBER:	66018-38-0
SOURCE/HOST:	Isolated from Deuteromycetes sp.
PURITY:	≥95% (HPLC)
APPEARANCE:	White to off-white solid.
SOLUBILITY:	Soluble in methanol, chloroform or ethil acetate.
SHIPPING:	AMBIENT
LONG TERM STORAGE:	-20°C

Product Description

Inhibitor of the JNK/p38 pathways. Inhibits anisomycin-induced but not TNF-induced JNK/p38 activation. Potent protein kinase inhibitor.

Product Specific Literature References

A radicicol-related macrocyclic nonaketide compound, antibiotic LL-Z1640-2, inhibits the JNK/p38 pathways in signal-specific manner: K. Takehana, et al.; BBRC 257, 19 (1999) Abstract
Inhibition of HgCl2-induced mitogen-activated protein kinase activation by LL-Z1640-2 in CCRF-CEM cells: M. Matsuoka, et al.; Eur. J. Pharmacol. 409, 155 (2000) Abstract
Cadmium induces phosphorylation of p53 at serine 15 in MCF-7 cells: M. Matsuoka & H. Igisu; BBRC 282, 1120 (2001) Abstract
Effects of pentachlorophenol and tetrachlorohydroquinone on mitogen-activated protein kinase pathways in Jurkat T cells: B. Wispriyono, et al.; Environ. Health Perspect. 110, 139 (2002) Abstract; Full Text
Pharmacological inhibitors of MAPK pathways: J.M. English & M.H. Cobb; TIPS 23, 40 (2002), (Review) Abstract
Suppression of cadmium-induced JNK/p38 activation and HSP70 family gene expression by LL-Z1640-2 in NIH3T3 cells: N. Sugisawa, et al.; Toxicol. Appl. Pharmacol. 196, 206 (2004) Abstract
JNK (c-Jun NH2 terminal kinase) and p38 during ischemia reperfusion injury in the small intestine: T. Murayama, et al.; Transplantation 81, 1325 (2006) Abstract
Involvement of the extracellular signal-regulated protein kinase pathway in phosphorylation of p53 protein and exerting cytotoxicity in human neuroblastoma cells (SH-SY5Y) exposed to acrylamide: T. Okuno, et al.; Arch. Toxicol. 80, 146 (2006) Abstract
Protein kinases as small molecule inhibitor targets in inflammation: M. Gaestel, et al.; Curr. Med. Chem. 14, 2214 (2007), (Review) Abstract
Chemistry and biology of resorcylic acid lactones: N. Winssinger & S. Barluenga; Chem. Commun. 1, 22 (2007), (Review) Abstract; Full Text

Further Categories Containing This Product:

JNK [SAPK1]/Related Products

ALX-380-210

Revised 08-Apr-08

7-Oxostaurosporine
SYNONYMS	Antibiotic BMY 41950 Antibiotic RK 1409 LCM76-L
PRODUCT LINE	Natural Products / Antibiotics
PRODUCT CATEGORY	Antibiotics - Protein Kinase Inhibitors

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-380-210-M001		1 mg	330.00 USD

Product Specification

FORMULA:	C₂₈H₂₄N₄O₄
MW:	480.5
CAS NUMBER:	141196-69-2
SOURCE/HOST:	Isolated from Streptomyces sp. MST-AS5345.
PURITY:	≥98% (HPLC)
APPEARANCE:	Yellow solid.
SOLUBILITY:	Soluble in DMSO, dimethyl formamide, methanol or 100% ethanol; slightly soluble in water.
SHIPPING:	AMBIENT
LONG TERM STORAGE:	-20°C

Product Description

Antibiotic. Potent inhibitor of protein kinase C (PKC). Inhibits the cell cycle at the G2 stage.

Product Specific Literature References

A new inhibitor of protein kinase C, RK-1409 (7-oxostaurosporine). I. Taxonomy and biological activity: H. Osada, et al.; J. Antibiot. 45, 189 (1992) Abstract
A new inhibitor of protein kinase C, RK-1409 (7-oxostaurosporine). II. Fermentation, isolation, physico-chemical properties and structure: H. Koshino, et al.; J. Antibiot. 45, 195 (1992) Abstract

Further Categories Containing This Product:

PKC Inhibitors • Cell Cycle Blockers & Inhibitors/Related Products • Staurosporine/Related Products • Antibiotics for Cell Cycle Research • Alkaloids

ALX-380-040

Revised 21-Feb-08

Polymyxin B . sulfate
PRODUCT LINE	Natural Products / Antibiotics
PRODUCT CATEGORY	Antibiotics - Protein Kinase Inhibitors

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-380-040-G001		1 g	58.00 USD
ALX-380-040-G005		5 g	205.00 USD

Product Specification

CAS NUMBER:	1405-20-5
MERCK INDEX:	14: 7573
RTECS:	TR1150000
SOURCE/HOST:	Isolated from Bacillus polymyxa.
APPEARANCE:	White to off-white powder.
PURITY DETAIL:	Mixture of Polymyxin B1, B2, B3 and B1-I.
SOLUBILITY:	Soluble in water.
ACTIVITY:	≥6000U/mg.
SHIPPING:	AMBIENT
LONG TERM STORAGE:	+4°C
HAZARD:	HARMFUL.
Polymyxin B₁

Product Description

Antibiotic. Inhibitor of protein kinase C (PKC). Breaks the bacterial membrane by incorporating into the phospholipid of the outer membrane and activating phospholipase.

Product Specific Literature References

Stimulus-dependent inhibition of platelet aggregation by the protein kinase C inhibitors polymyxin B, H-7 and staurosporine: C. Schächtele, et al.; BBRC 151, 542 (1988) Abstract
Membrane interactions of amphiphilic polypeptides mastoparan, melittin, polymyxin B & cardiotoxin. Differential inhibition of PKC, CaMKII & synaptosomal membrane Na,K-ATPase & Na+ pump & differentiation of HL60 cells.: R.L. Raynor, et al.; J. Biol. Chem. 266, 2753 (1991) Abstract; Full Text
Inhibitors such as staurosporine, H-7 or polymyxin B cannot be used in skeletal muscle to prove the role of protein kinase C on insulin action: A. Guma, et al.; Biosci. Rep. 12, 413 (1992) Abstract
Volume-regulatory Cl- channel currents in cultured human epithelial cells: M. Kubo & Y. Okada; J. Physiol. 456, 351 (1992) Abstract
Gap junctional conductance tunes phase difference of cholecystokinin evoked calcium oscillations in pairs of pancreatic acinar cells: A. Ngezahayo & H.A. Kolb; Pfluegers Arch. 422, 413 (1993) Abstract
Direct effects of polymyxin B on human dendritic cells maturation. The role of IkappaB-alpha/NF-kappaB and ERK1/2 pathways and adhesion: B. Valentinis, et al.; J. Biol. Chem. 280, 14264 (2005) Abstract
Modulation of P2X7 receptor functions by polymyxin B: crucial role of the hydrophobic tail of the antibiotic molecule: D. Ferrari, et al.; Br. J. Pharmacol. 150, 445 (2007) Abstract
Polymyxin antibiotics for gram-negative infections: T. M. Arnold, et al.; Am. J. Health Syst. Pharm. 64, 819 (2007), Review Abstract

Further Categories Containing This Product:

PKC Inhibitors

ALX-380-092

Revised 03-Jul-08

Radicicol
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
ALX-380-092-M005		5 mg	295.00 USD

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. p60^v-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, 231