|Catalog||Product Name||CAS Number|
|17-AEP-GA, an HSP90 antagonist, is a potent inhibitor of glioblastoma cell proliferation, survival, migration and invasion. ADCs Toxin.|
|Aminohexylgeldanamycin (AHGDM), a Geldanamycin derivative, is a potent HSP90 inhibitor. Aminohexylgeldanamycin shows antiangiogenic and antitumor activities.|
|17-GMB-APA-GA is an ADC Cytotoxin. 17-GMB-APA-GA is a potent HSP90 inhibitor and used for latent T. gondii infection research.|
BOC Sciences established advanced high throughput ADCs cytotoxins production platform to meet the increasing demand for ADC researches.
Heat shock protein 90 (HSP90) is an essential molecular chaperone in the protein quality control (PQC) system, acting in client-protein folding, regulation, and protein complexes assembly. Additionally, HSP90 is essential for eukaryotic cell growth. HSP90 is a hub protein that interacts with over 10% of the proteome, representing 1%-3% of cytoplasmatic soluble proteins in mammalian cells at physiological conditions. Since HSP90 is abundantly expressed in tumor types, it stabilizes various proteins required for cancer cell survival and has been identified as a promising drug target for cancer treatment. Up to date, several HSP90 inhibitors have entered into clinical trials.
Heat shock protein 90 (HSP90) is a dimeric protein, and each protomer was composed of three domains that have characteristic features: the nucleotide-binding N-terminal domain, the client-protein interaction Middle (M) domain, and the dimerization C-terminal domain. Mechanistically, the N and M domains are connected by a flexible charged linker, which is important for protein dynamics and ATPase activity. Two residues that participate the TP hydrolysis, R380 and Q384 (yeast Hsp82 numbering) are located at the M domain. The C-terminal contains the MEEVD motif responsible for the interaction with TPR co-chaperones. Finally, all hydrophobic exposed surfaces, which are important for client-protein interaction, are present in all three domains of HSP90s. The ATPase activity of HSP90 is essential for the protein in vivo activity. Most HSP90 inhibitors that have been clinically studied were identified to bind to the ATP-binding domain in the N-terminus. Owing to the importance of HSP90 in cellular proteins regulation, it has become a promising drug target for the treatment of several diseases, including cancer and diseases associated with protein misfolding.
Fig. 1. Schematic diagram of heat shock protein 90 (Bioorganic & Medicinal Chemistry 2019, 27, 12, 115080).
Heat shock protein 90 (HSP90) is abundantly expressed by various tumor types and has been recently targeted for cancer therapy. HSP90 inhibits cancer cell proliferation by depleting client oncoproteins and shutting down multiple oncogenic pathways. Therefore, it is an attractive strategy for targeting human cancers. Several HSP90 inhibitors, including AUY922 and STA9090, show promising effects in clinical trials. Aminohexylgeldanamycin (AHGDM), a Geldanamycin derivative, is a potent HSP90 inhibitor. In general, these inhibitors act as ATP competitors and interfere with ATP-binding domain, which inhibit HSP90 and lead to ubiquitination and proteasome degradation due to aberrant conformation. Because Aminohexylgeldanamycin shows antiangiogenic and antitumor activities, it is widely applied in the development of antibody-drug conjugate (ADC).