Geldanamycin & Analogues

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Geldanamycin

17AAG

17DMAG

References

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This page was prepared by the students of applied biochemistry, OpenUniversity, BirZeith.

Geldanamycin is a benzoquinone ansamycin, a family of antibiotics originally isolated on the basis of their weak antibiotic activity that were subsequently shown to display potent antitumor activity. Geldanamycin induces the degradation of proteins that are mutated in tumor cells such as v-src, bcr-abl and p53 preferentially over their normal cellular counterparts. This effect is mediated via HSP90. Despite its potent antitumor potential, Geldanamycin presents several major drawbacks as a drug candidate that have led to the development of Geldanamycin analogues, in particular analogues containing a substitution on the 17-alkylamino radical:
• 17-AAG
• 17-DMAG

Geldanamycin

Description

Geldanamycin is a natural product produced by Streptomyces hygroscopicus in submerged fermentation. InvivoGen claim they make Geldanamycin from a mutant strain of Streptomyces hygroscopicus, inactivated for the synthesis of Nigericin. The Nigericin is an interesting compound by itself. Fermentek produces Nigericin as a molecular biology reagent. Fermentek claim they use no mutants, but native unmodified strains only, as a matter of company policy. Geldanamycin binds with high affinity into the ATP binding pocket of Hsp 90. Hsp 90 is a ubiquitous molecular chaperone critical for the folding, assembly and activity of multiple mutated and overexpressed signaling proteins that promote the growth and/or survival of tumor cells. Hsp 90 target proteins include mutated p53, Raf-1, Akt, ErbB2 and hypoxia-inducible factor 1a (HIF-1a). Binding of Geldanamycin to Hsp 90 causes the destabilization and degradation of its client proteins.

Formula: C29H40N2O9

Molecular weight: 560.64

CAS Number : 30562-34-6

Appearance: yellow powder

17-AAG

Description

17-Allylamino-17-demethoxygeldanamycin (17-AAG) is an analogue chemically derived from GA. 17-AAG is a less toxic and more stable analogue of geldanamycin (GA). Even though 17-AAG binding to Hsp90 is weaker than GA, 17-AAG displays similar antitumor effects as GA and a better toxicity profile. 17-AAG is currently in phase I clinical trial in several centers worldwide. Preliminary data obtained from these trials demonstrate that antitumor activity is achieved at concentrations below the maximum tolerated dose.

Formula: C31H43N3O8

Molecular weight: 585.69

CAS Number : 75747-14-7

Appearance: purple powder

17-DMAG

Description

17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG, NSC 707545) is the first water-soluble analogue of 17-AAG. This Hsp90 inhibitor shows promise in preclinical models. 17-DMAG has excellent bioavailability, is widely distributed to tissues, and is quantitatively metabolized much less than is 17-AAG.

Formula: C₃₂H₄₈N₄O₈, HCl

Molecular weight: 652

The USA government claimed rights on 17-DMAG; see United States Patent 6,890,917 Snader , et al. May 10, 2005. It is remarkable that none of the producers and resellers of 17DMAG declare they have license to make it.

Primary manufacturers of Geldanamycin and derivates thereof:

InvivoGen; 3950 Sorrento Valley Blvd, Suite A San Diego, California 92121,
USA Toll-free: 888 457 5873 Tel: 858 457 5873 Fax: 858 457 5843

Fermentek biotechnology; 25 Yatziv st, Atarot industrial zone, Jerusalem Israel
tel 972-2-5853953; fax 972 2 5853943

Biomol; 5120 Butler Pike; Plymouth Meeting, PA 19462

We have seen on AliBaba some chinese that claimed they COULD make Geldanamycin, but strangely enough, Geldanamycin was not listed on their catalog when we came closer.

Disclaimer:

This page was made by the students of bioinformatics, the OpenUniversity, BirZeit P.A., as a homework in the Survival in the iJungle. It has no intelectual value whatsoever.

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HABASAR

Links of the YOLL itself
We must have at least 100 pages here.

Here come some links to top-rated hrefs, such as Microsoft, wikipedia, Google and Yahoo :google, microsoft, yahoo, wikipedia

Now come links to these of fermentek product pages, that are needy : .the homepage of fermentek, FK506 or tacrolimus, products of Fermentek: staurosporine, K252A, aflatoxin, Sirolimus (Rapamycin)

And other link beggars:

Tinnitus. about some guys that had tinnitus

Nonactin at noneto. Some facts about nonactin. Why nobody needs it. Who is prof Nigel mister nonactin, and what is his role in promiliad

fer