30562-34-6 Usage
Description
Geldanamycin, a benzoquinone ansamycin antibiotic, is derived from Streptomyces hygroscopicus. It exhibits a chemical structure characterized by a benzenoid ring and is presented as a yellow to orange powder. Geldanamycin specifically binds to heat shock protein 90 (Hsp90) and its endoplasmic reticulum homologue GP96, playing a crucial role in the conformational maturation, stability, and cellular stress response of various proteins. It also acts as a potent inhibitor of the nuclear hormone receptor family and has demonstrated antiproliferative and antitumor effects.
Uses
Used in Anticancer Applications:
Geldanamycin is utilized as an antitumor agent, showing potent activity against 60 cell lines at nanomolar concentrations. It targets the Hsp90 chaperone, which is essential for the activation of several proto-oncogenic and nuclear hormone receptor families, thereby inhibiting the conformational maturation and cellular stress response of these proteins. Geldanamycin has demonstrated efficacy in mouse tumor models and has shown promise in cancer therapy.
Used in Pharmaceutical Industry:
Geldanamycin is employed as an inhibitor of proto-oncogenic protein kinases, such as erbB2, EGF receptor tyrosine kinases, and non-receptor tyrosine kinases like v-src and Raf-1. It also inhibits the nuclear hormone receptor family, including estrogen and androgen hormone receptors. Its ability to interfere with the actions of these proteins makes it a valuable compound in the development of cancer therapeutics.
Used in Research and Development:
Geldanamycin's interaction with Hsp90 and its paralog GRP94 allows it to indirectly affect numerous client proteins involved in various cellular processes, such as gene expression, cell proliferation, apoptosis, and angiogenesis. This makes it a valuable tool in research and development for understanding the roles of these proteins in cancer and other diseases.
Used in Drug Discovery:
As a potent inhibitor of Hsp90, geldanamycin serves as a starting point for the development of new drugs targeting this protein. Its chemical properties and binding specificity make it a promising candidate for the design of novel therapeutic agents with improved efficacy and reduced side effects.
Biological Activity
Selectively inhibits heat shock protein 90 (Hsp90). Binds to the ATP site of Hsp90 (K d = 1.2 μ M) and inhibits its chaperone activity. Consequently inhibits activities of oncogenic kinases (e.g. src, Raf), p53 and steroid receptors.
Biochem/physiol Actions
Primary Targetpc60c-svc tyrosine kinase
References
1) Neckers et al. (1999), Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity; Invest. New Drugs, 17 361
2) Zang et al. (2006), HSP90 protects apoptotic cleavage of vimentin in geldanamycin-induced apoptosis; Mol. Cell. Biochem., 281 111
Check Digit Verification of cas no
The CAS Registry Mumber 30562-34-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,0,5,6 and 2 respectively; the second part has 2 digits, 3 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 30562-34:
(7*3)+(6*0)+(5*5)+(4*6)+(3*2)+(2*3)+(1*4)=86
86 % 10 = 6
So 30562-34-6 is a valid CAS Registry Number.
InChI:InChI=1/C29H40N2O9/c1-15-11-19-25(34)20(14-21(32)27(19)39-7)31-28(35)16(2)9-8-10-22(37-5)26(40-29(30)36)18(4)13-17(3)24(33)23(12-15)38-6/h8-10,13-15,17,22-24,26,33H,11-12H2,1-7H3,(H2,30,36)(H,31,35)/b10-8-,16-9+,18-13+/t15-,17+,22+,23+,24-,26+/m1/s1
30562-34-6Relevant articles and documents
Synthesis of novel geldanamycin derivatives
Kitson, Russell R.A.,Moody, Christopher J.
, (2021/02/03)
The toxicity associated with the geldanamycin family of benzoquinone ansamycins when used as heat shock protein-90 inhibitor molecular therapeutics is ameliorated by substitution at the 19-position. The resulting 19-substituted derivatives have greater potential for success in oncology clinical trials and for other medicinal purposes such as the treatment of neurodegenerative conditions. Having overcome hurdles associated with the sensitivity and complexity of these molecules, through a variety of synthetic approaches, the synthesis of a series of 19-substituted geldanamycin derivatives is reported herein using optimised Stille and Suzuki coupling reactions. Further compounds were accessible via copper-mediated coupling and nucleophilic addition reactions The new compounds are of significant medicinal interest, in view of their significantly reduced toxicity previously observed for this class of substrate compared to their 19-unsubstituted counterparts that have been evaluated in the clinic.
