ALEXIS Biochemicals: Polyclonal Antibody to HSP86

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ALX-350-029

Revised 07-Oct-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.

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. Neurotoxic.

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

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-380-091

Revised 21-Aug-08

17-AAG
SYNONYMS	17-(Allylamino)-17-desmethoxygeldanamycin
PRODUCT LINE	Natural Products / Antibiotics
PRODUCT CATEGORY	Antitumor Antibiotics

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-380-091-C100		100 µg	65.00 USD
ALX-380-091-M001		1 mg	162.00 USD

Product Specification

FORMULA:	C₃₁H₄₃N₃O₈
MW:	585.7
CAS NUMBER:	75747-14-7
SOURCE/HOST:	Semisynthetic derivative from geldanamycin.
PURITY:	≥97%
APPEARANCE:	Red to dark red powder.
SOLUBILITY:	Soluble in DMSO (10mg/ml) or methanol (10mg/ml).
SHIPPING:	AMBIENT
LONG TERM STORAGE:	-20°C
HANDLING:	Protect from light.

Product Description

Potent, less toxic derivative of geldanamycin (Prod. No. ALX-380-054). Inhibits the essential ATPase activity of HSP90. Inhibitor of telomerase activity. Inducer of apoptosis with antitumor activity.

Product Specific Literature References

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
The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin: T.W. Schulte & L.M. Neckers; Cancer Chemother. Pharmacol. 42, 273 (1998) Abstract
Gene expression profiling of human colon cancer cells following inhibition of signal transduction by 17-allylamino-17-demethoxygeldanamycin, an inhibitor of the hsp90 molecular chaperone: P.A. Clarke, et al.; Oncogene 19, 4125 (2000) Abstract
Geldanamycin and its analogue 17-allylamino-17-demethoxygeldanamycin lowers Bcr-Abl levels and induces apoptosis and differentiation of Bcr-Abl-positive human leukemic blasts: R. Nimmanapalli, et al.; Cancer Res. 61, 1799 (2001) Abstract; Full Text
Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells: P.N. Munster, et al.; Cancer Res. 61, 2945 (2001) Abstract; Full Text
Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin: J. Yang, et al.; Cancer Res. 61, 4010 (2001) Abstract; Full Text
Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: in vitro and in vivo analysis: D.M. Nguyen, et al.; Ann. Thorac. Surg. 72, 371 (2001) Abstract
ErbB2 degradation mediated by the co-chaperone protein CHIP: P. Zhou, et al.; J. Biol. Chem. 278, 13829 (2003) 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
Geldanamycin and its 17-allylamino-17-demethoxy analogue antagonize the action of Cisplatin in human colon adenocarcinoma cells: differential caspase activation as a basis for interaction: I.A. Vasilevskaya, et al.; Cancer Res. 63, 3241 (2003) Abstract
A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors: A. Kamal, et al.; Nature 425, 407 (2003) Abstract
Chaperoning oncogenes: HSP90 as a target of geldanamycin: L. Neckers; Handb. Exp. Pharmacol. 259 (2006) Abstract
Drugging the cancer chaperone HSP90: Combinatorial therapeutic exploitation of oncogene addiction and tumor stress: P. Workman, et al.; Ann. N.Y. Acad. Sci. 1113, 202 (2007) Abstract
Synergism between etoposide and 17-AAG in leukemia cells: critical roles for Hsp90, FLT3, topoisomerase II, Chk1, and Rad51: Q. Yao, et al.; Clin. Cancer Res. 13, 1591 (2007) Abstract; Full Text
Phase I and pharmacodynamic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with refractory advanced cancers: R.K. Ramanathan, et al.; Clin. Cancer Res. 13, 1769 (2007) Abstract
HSP90 inhibitor 17AAG causes apoptosis in ATRA-resistant acute promyelocytic leukemia cells: P.N. Meyer, et al.; Leuk. Res. 32, 143 (2008) Abstract
Intratumor injection of the Hsp90 inhibitor 17AAG decreases tumor growth and induces apoptosis in a prostate cancer xenograft model: C.R. Williams, et al.; J. Urol. 178, 1528 (2007) Abstract
Rituximab and 17-allylamino-17-demethoxygeldanamycin induce synergistic apoptosis in B-cell chronic lymphocytic leukaemia: A.J. Johnson, et al.; Br. J. Haematol. 139, 837 (2007) Abstract
An in vitro and in vivo study of the combination of the heat shock protein inhibitor 17-allylamino-17-demethoxygeldanamycin and carboplatin in human ovarian cancer models: U. Banerji, et al.; Cancer Chemother. Pharmacol. 62, 769 (2008) Abstract

Further Categories Containing This Product:

Antibiotics - Apoptosis Inducers & Inhibitors • Tyrosine Kinase Inhibitors • Antibiotics - Other Signal Transduction Pathway Modulators • Antitumor Agents (Enzyme Inhibitors) • HSP90 / HtpG / Related Products

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, 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

Further Categories Containing This Product:

Tyrosine Kinase Inhibitors • Cell Cycle Blockers & Inhibitors / Related Products • Estrogen & Estrogen Receptors / Related Products • Antibiotics - Nitric Oxide Pathway Modulators • Antitumor Agents (Hormone-related) • NF-kB Pathway Inhibitors • Malaria / Related Products • Antibiotics - Antimalarial • Antibiotics - Protein Kinase Inhibitors • Antibiotics - NF-kB Inhibitors • Antibiotics for Angiogenesis Research • Antibiotics for Cell Cycle Research • HSP90 / HtpG / Related Products • Antibiotics - Topoisomerase Inhibitors • RNA Polymerases / Related Products

ALX-380-093

Revised 16-Jun-08

Novobiocin . sodium salt
SYNONYMS	Albamycin Streptonivicin N-[7-[[3-O-Aminocarbonyl-6-deoxy-5-C-methyl-4-O-β-L-lyxo-hexapyranosyl]oxy]-4-hydroxy-8-methyl-2-oxo-2H-1-benzopyran-3-yl]-4-hydroxy-3-(3-methyl-2-butenyl)benzamide
PRODUCT LINE	Natural Products / Antibiotics
PRODUCT CATEGORY	Antibiotics - Other Signal Transduction Pathway Modulators

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-380-093-G001		1 g	30.00 USD

Product Specification

FORMULA:	C₃₁H₃₅N₂O₁₁ . Na
MW:	611.6 . 23.0
CAS NUMBER:	1476-53-5
MERCK INDEX:	14: 6722
RTECS:	RD5425000
PURITY:	≥95%
APPEARANCE:	White to pale yellow solid.
SOLUBILITY:	Soluble in water (100mg/ml).
SHIPPING:	AMBIENT
LONG TERM STORAGE:	+4°C
HANDLING:	Protect from light.
HAZARD:	HARMFUL. IRRITANT.

Product Description

Antibiotic. Inhibitor of HSP90. Interacts with the C-terminal ATP-binding domain of HSP90 in contrast to the benzoquinone ansamycins 17-AAG (Prod. No. ALX-380-091), geldanamycin (Prod. No. ALX-380-054), herbimycin A (Prod. No. ALX-350-029), and the chemically unrelated radicicol (Prod. No. ALX-380-092), which bind to the N-terminal ATP-binding site of HSP90. Inhibitor of DNA gyrase. Useful for the production of positively supercoiled plasma DNA, targeting the nucleotide-binding site of gyrase B. Inhibits retrovirus RNA-dependent DNA polymerase. Potent inhibitor of ADP ribosylation. Inhibits LPS-induced production of pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6 and IL-10. Inhibits protein synthesis and alters the phosphorylation state of several cytosolic proteins. Reverses etoposide resistance in non-P-glycoprotein expressing multidrug resistant (MDR) tumor cell lines. Inducer of CD38 on cells of the myelomonocytic lineage. Forms ion channels in lipid bilayers.

Product Specific Literature References

Novobiocin-a specific inhibitor of semiconservative DNA replication in permeabilized Escherichia coli cells: W.L. Staudenbauer; J. Mol. Biol. 96, 201 (1975) Abstract
Novobiocin and coumermycin inhibit DNA supercoiling catalyzed by DNA gyrase: M. Gellert, et al.; PNAS 73, 4474 (1976) Abstract; Full Text
Energy coupling in DNA gyrase and the mechanism of action of novobiocin: A. Sugino, et al.; PNAS 75, 4838 (1978) Abstract; Full Text
Effect of novobiocin and other DNA gyrase inhibitors on virus replication and DNA synthesis in herpes simplex virus type 1-infected BHK cells: B. Francke and J. Margolin; J. Gen. Virol. 52, 401 (1981) Abstract; Full Text
Inhibition of retrovirus RNA-dependent DNA polymerase by novobiocin and nalidixic acid: Y. Sumiyoshi, et al.; J. Gen. Virol. 64, 2329 (1983) Abstract
Positively supercoiled plasmid DNA is produced by treatment of Escherichia coli with DNA gyrase inhibitors: D. Lockshon and D.R. Morris; Nucleic Acids Res. 11, 2999 (1983) Abstract
Structure-activity relationships in DNA gyrase inhibitors: S. Radl; Pharmacol. Ther. 48, 1 (1990), (Review) Abstract
Reversal of etoposide resistance in non-P-glycoprotein expressing multidrug resistant tumor cell lines by novobiocin: G. Rappa, et al.; Cancer Res. 53, 58487 (1993) Abstract
The properties of ion channels formed by the coumarin antibiotic, novobiocin, in lipid bilayers: A.M. Feigin, et al.; Biochim. Biophys. Acta 1234, 43 (1995) Abstract
Mechanism of inhibition of vaccinia DNA topoisomerase by novobiocin and coumermycin: J. Sekiguchi, et al.; J. Biol. Chem. 271, 2313 (1996) Abstract; Full Text
Immunomodulating properties of the antibiotic novobiocin in human monocytes: A. Luhrmann, et al.; Antimicrob. Agents Chemother. 42, 1911 (1998) Abstract; Full Text
Novobiocin and related coumarins and depletion of heat shock protein 90-dependent signaling proteins: M.G. Marcu, et al.; J. Natl. Cancer Inst. 92, 242 (2000) Abstract
The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone: M.G. Marcu, et al.; J. Biol. Chem. 275, 37181 (2000) Abstract; Full Text
Novobiocin is a novel inducer of CD38 on cells of the myelomonocytic lineage: A. Thiele, et al.; Biochim. Biophys. Acta 1542, 32 (2002) Abstract
Evidence that the novobiocin-sensitive ATP-binding site of the heat shock protein 90 (hsp90) is necessary for its autophosphorylation: T. Langer, et al.; Cell Biol. Int. 26, 653 (2002) Abstract
Alteration of Escherichia coli topoisomerase IV to novobiocin resistance: C.D. Hardy and N.R. Cozzarelli; Antimicrob. Agents Chemother. 47, 941 (2003) Abstract; Full Text
Active-site residues of Escherichia coli DNA gyrase required in coupling ATP hydrolysis to DNA supercoiling and amino acid substitutions leading to novobiocin resistance: C.H. Gross, et al.; Antimicrob. Agents Chemother. 47, 1037 (2003) Abstract; Full Text
A coumermycin/novobiocin-regulated gene expression system: H.F. Zhao, et al.; Hum. Gene Ther. 14, 1619 (2003) Abstract
Destabilization of the non-pathogenic, cellular prion-protein by a small molecular drug: H.J. Ochel and G. Gademann; Antivir. Ther. 9, 441 (2004) Abstract
Novobiocin induces a distinct conformation of Hsp90 and alters Hsp90-cochaperone-client interactions: B.G. Yun, et al.; Biochemistry 43, 8217 (2004) Abstract
Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90: J.A. Burlison, et al.; JACS 128, 15529 (2006) Abstract

Further Categories Containing This Product:

Anti-inflammatory Agents Other Products • HSP90 / HtpG / Related Products • Antibiotics - Topoisomerase Inhibitors • Protein Synthesis Other Products

ALX-380-110

Revised 03-Apr-08

17-DMAG
SYNONYMS	17-[2-(Dimethylamino)ethyl]amino-17-desmethoxygeldanamycin NSC 707545
PRODUCT LINE	Natural Products / Antibiotics
PRODUCT CATEGORY	Antibiotics for Angiogenesis Research

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-380-110-C100		100 µg	50.00 USD
ALX-380-110-M001		1 mg	150.00 USD

Product Specification

FORMULA:	C₃₂H₄₈N₄O₈
MW:	616.8
CAS NUMBER:	150270-08-9
SOURCE/HOST:	Semisynthetic from geldanamycin (Prod. No. ALX-380-054).
PURITY:	≥99%
APPEARANCE:	Purple to black powder.
SOLUBILITY:	Soluble in water, 100% ethanol (10mg/ml) or DMSO (>25mg/ml).
SHIPPING:	AMBIENT
LONG TERM STORAGE:	-20°C
HANDLING:	Protect from light.

Product Description

Less toxic, more potent synthetic derivative of geldanamycin. Inhibitor of angiogenesis. Inhibitor of heat shock protein 90 (HSP90). Inducer of apoptosis with higher antitumor activity than 17-AAG (Prod. No. ALX-380-091).

Product Specific Literature References

Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 rats: M.J. Egorin, et al.; Cancer Chemother. Pharmacol. 49, 7 (2002) Abstract
Biliary excretion of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) and metabolites by Fischer 344 rats: S.M. Musser, et al.; Cancer Chemother. Pharmacol. 52, 139 (2003) Abstract
Crystal structure and molecular modeling of 17-DMAG in complex with human Hsp90: J.M. Jez, et al.; Chem. Biol. 10, 361 (2003) Abstract
Synthesis and biological activities of novel 17-aminogeldanamycin derivatives: Z.Q. Tian, et al.; Bioorg. Med. Chem. 12, 5317 (2004) Abstract
Antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: an orally bioavailable heat shock protein 90 modulator: G. Kaur, et al.; Clin. Cancer Res. 10, 4813 (2004) Abstract
Enhanced tumor cell radiosensitivity and abrogation of G2 and S phase arrest by the Hsp90 inhibitor 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin: E.E. Bull, et al.; Clin. Cancer Res. 10, 8077 (2004) Abstract
ErbB3 expression predicts tumor cell radiosensitization induced by Hsp90 inhibition: H. Dote, et al.; Cancer Res. 65, 6967 (2005) Abstract
In vivo antitumor efficacy of 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride), a water-soluble geldanamycin derivative: M. Hollingshead, et al.; Cancer Chemother. Pharmacol. 56, 115 (2005) Abstract
Comparison of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17DMAG) and 17-allylamino-17-demethoxygeldanamycin (17AAG) in vitro: effects on Hsp90 and client proteins in melanoma models: V. Smith, et al.; Cancer Chemother. Pharmacol. 56, 126 (2005) Abstract
Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs: potential clinical relevance: E.R. Glaze, et al.; Cancer Chemother. Pharmacol. 56, 637 (2005) Abstract
17-Allyamino-17-demethoxygeldanamycin and 17-NN-dimethyl ethylene diamine-geldanamycin have cytotoxic activity against multiple gynecologic cancer cell types: D.R. Gossett, et al.; Gynecol. Oncol. 96, 381 (2005) Abstract
Structure-based design of 7-carbamate analogs of geldanamycin: G. Rastelli, et al.; Biooorg. Med. Chem. Lett. 15, 5016 (2005) Abstract
Generation of a novel anti-geldanamycin antibody: E. Barzilay, et al.; BBRC 330, 561 (2005) Abstract
Determination of the heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin in plasma by liquid chromatography-electrospray mass spectrometry: K. Hwang, et al.; J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 830, 35 (2006) Abstract