467214-20-6

Basic information

• Product Name: Alvespimycin
• Synonyms: 17-DIMETHYLAMINOETHYLAMINO-17-DEMETHOXYG;17-DMAGhydrochloride;17-[2-(Dimethylamino)ethylamino]-17-desmethylgeldanamycin;17-Demethoxy-17-[[2-(dimethylamino)ethyl]amino]geldanamycin;Alvespimycin;17-DMAG (Alvespimycin);17-DMAG;Unii-001L2fe0m3
• CAS NO: 467214-20-6
• Molecular Formula: C₃₂H₄₈N₄O₈
• Molecular Weight: 616.74552
• Product Categories: Amines;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Isotope Labelled Compounds
• Mol File: 467214-20-6.mol
• Article Data: 4

Chemical Properties

• Appearance: /
• Density: 1.20
• Storage Temp.: Desiccate at -20°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: Alvespimycin(CAS DataBase Reference)
• NIST Chemistry Reference: Alvespimycin(467214-20-6)
• EPA Substance Registry System: Alvespimycin(467214-20-6)

Safety Data

• Hazardous Substances Data: 467214-20-6(Hazardous Substances Data)

Usage

Description

Alvespimycin, also known as 17-DMAG, is a water-soluble derivative of Geldanamycin, a 19-membered macrocyclic compound. It is an analogue of Gelamycin (G304500) and 17-(Allylamino)geldanamycin (A549650). Alvespimycin acts as a potent Hsp90 inhibitor with an IC50 of 24 nM, exhibiting excellent bioavailability and tissue distribution in animals. It possesses diverse anti-tumor actions and has potential in treating certain types of cancer. Additionally, it suppresses inflammation by interfering with the NF-κB signaling pathway and ameliorates high fat diet-induced renal failure in a mouse model of diabetes.

Uses

Used in Anticancer Applications:
Alvespimycin is used as an anticancer agent for its potent Hsp90 inhibitory activity, which displays more potent antitumor activity than 17-AAG. It has potential in treating certain types of cancer due to its diverse anti-tumor actions.
Used in Inflammation Suppression:
Alvespimycin is used as an anti-inflammatory agent for its ability to interfere with signaling through the NF-κB pathway, which helps in suppressing inflammation.
Used in Renal Failure Treatment:
Alvespimycin is used as a treatment for high fat diet-induced renal failure in a mouse model of diabetes, as it has been shown to ameliorate the condition.
Used in Pharmaceutical Industry:
Alvespimycin is used as a Hsp90 inhibitor for the development of novel drug delivery systems, aiming to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles have been employed as carriers for Alvespimycin delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.

Biological Activity

Water-soluble analog of 17-AAG (17-Demethoxy-17-(2-propenylamino)geldanamycin ) and geldanamycin (9,13-Dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-2-azabicyclo[16.3.1]docosa-4,6,10,18,21-pentaene-3,20,22-trione, 9-carbamate ). Binds the ATP binding site of Hsp90 and inhibits its chaperone activity. Displays more potent antitumor activity than 17-AAG (mean GI 50 values are 53 and 123 nM for 17-DMAG and 17-AAG respectively).

Upstream product

• 108-00-9 N,N-dimethylethylenediamine 
• 30562-34-6 geldanmycin 

Downstream Products

• 1427297-14-0 (R)-methyl-2-acetamido-3-((4E,6Z,8S,9S,10E,12S,13R,14S,16R)-9-(carbamoyloxy)-19-(2-(dimethylamino)ethylamino)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1⁽²¹⁾,4,6,10,18-pentaen-21-ylthio)propanoate 
• 1353249-59-8 C₄₂H₆₅N₇O₁₄S 
• 1353249-38-3 C₃₁H₄₆N₄O₈ 
• 574717-99-0 C₃₂H₄₈N₄O₉ 
• 497860-87-4 17-[2-(dimethylamino)ethylamino]-11-oxo-17-demethyoxygeldanamycin 
• 1158795-64-2 C₃₆H₅₀N₆O₉ 
• 1013925-04-6 17-demethoxy-17-(dimethylaminoethylamino)geldanamycin-18-oxime 
• 868174-42-9 (4E,6Z,10E)-(8S,9S,12S,13R,14S,16R)-19-(2-Dimethylamino-ethylamino)-9,13-dihydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-2-aza-bicyclo[16.3.1]docosa-1⁽²¹⁾,4,6,10,18-pentaene-3,20,22-trione 

Relevant articles and documents

Synthesis and biological activities of novel 17-aminogeldanamycin derivatives

A library of over sixty 17-alkylamino-17-demethoxygeldanamycin were synthesized. Their affinity for Hsp90, ability to inhibit growth of SKBr3 mammalian cells, and in selected cases, water solubility, were measured. The structure-activity relationships of binding affinity to Hsp90 and cytotoxicity in SKBr3 cells are discussed. Geldanamycin interferes with the action of heat shock protein 90 (Hsp90) by binding to the N-terminal ATP binding site and inhibiting an essential ATPase activity. In a program directed toward finding potent, water soluble inhibitors of Hsp90, we prepared a library of over sixty 17-alkylamino-17-demethoxygeldanamycin analogs, and compared their affinity for Hsp90, ability to inhibit growth of SKBr3 mammalian cells, and in selected cases, water solubility. Over 20 analogs showed cell growth inhibition potencies similar to that of 17-allylamino-17-demethoxygeldanamycin (17-AAG), the front-runner geldanamycin analog that is currently in multiple clinical trials. Many of these analogs showed water solubility properties that were desirable for formulation. One of the most potent and water-soluble analogs in the series was 17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin (17-DMAG), which was independently prepared by the NCI and will soon enter clinical trials. Importantly, the binding affinity of these analogs to the molecular target Hsp90 does not correlate well with their cytotoxicity in SKBr3 cells.

Structure-based design of 7-carbamate analogs of geldanamycin

The 7-carbamate groups of geldanamycin and its 17-(2-dimethylaminoethyl) amino-17-demethoxy derivative (17-DMAG) bind the N-terminal domain of Hsp90 by establishing a network of hydrogen bonds which involve four buried water molecules. In this study, a structure-based approach was used to investigate the effects of displacing some of these waters by modification of the 7-carbamate. A general loss of binding to human Hsp90 was observed, except for replacement of the carbamate with a hydroxamate group which gave an analog with weak activity. Modeling of Hsp90-ligand interactions suggested that the hydroxamate was not able to displace the buried water molecules, while bulkier substituents able to do so proved inactive.