37927-01-8Relevant articles and documents
PREPARATION AND BIOLOGICAL ACTIVITY OF ANDROSTANE 17&β-CARBOXYLIC ACIDS
Gerasimova, M. L.,Gusarova, T. I.,Nikitin, V. B.,Engalycheva, G. N.,Kaminka, M. E.,Kuleshova, E. F.
, p. 896 - 899 (1989)
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Design, Synthesis, and Biological Evaluation of Dexamethasone-Salvianolic Acid B Conjugates and Nanodrug Delivery against Cisplatin-Induced Hearing Loss
Ye, Ruiqin,Sun, Lifang,Peng, Jinghui,Wu, Aixin,Chen, Xiaozhu,Wen, Lu,Bai, Chuan,Chen, Gang
, p. 3115 - 3130 (2021)
Cisplatin (CDDP) is an extensively used chemotherapeutic agent but has a high incidence of severe ototoxicity. Although a few molecules have entered clinical trials, none have been approved to prevent or treat CDDP-induced hearing loss by the Food and Drug Administration. In this study, an amphiphilic drug-drug conjugate was synthesized by covalently linking dexamethasone (DEX) and salvianolic acid B (SAL) through an ester or amide bond. The conjugates could self-assemble into nanoparticles (NPs) with ultrahigh drug loading capacity and favorable stability. Compared with DEX, SAL, or their physical mixture at the same concentrations, both conjugates and NPs showed enhanced otoprotection in vitro and in vivo. More importantly, the conjugates and NPs almost completely restored hearing in a guinea pig model with good biocompatibility. Immunohistochemical analyses suggested that conjugates and NPs activated the glucocorticoid receptor, which may work as one of the major mechanisms for their protective effects.
Cationic lipid-conjugated dexamethasone as a selective antitumor agent
Sau, Samaresh,Banerjee, Rajkumar
, p. 433 - 447 (2014)
Dexamethasone (Dex) is one of the highly potent synthetic glucocorticoids. It exhibits prominent anti-inflammatory but moderate anti-proliferative activities. It is widely used along side chemotherapy to alleviate toxic side effects. Additionally, Dex is also a potent inducer of gluconeogenesis. However, its overuse critically desensitizes cells against chemotherapy. Herein, we report on the development of a new class of cationic lipid-Dex conjugates in which the C-8 carbon chain analogue (DX8) exhibited glucocorticoid receptor (GR)-mediated, caspase-3-assisted, cancer cell-selective anti-proliferative activity. Melanoma tumors in DX8-treated mice exhibited significantly reduced tumor aggressiveness with respect to tumors in Dex-treated mice. Tumor lysates prepared from DX8-treated group showed elevated levels of p53. DX8-treated cancer cells showed clear degradation of kinase JAK3/STAT3 protein levels. Additionally, DX8-treatment decreased the level of VEGFR2 in tumor-endothelial cells implying DX8's anti-proliferative roles in both tumor cells and tumor neovascular cells. Collectively, our results demonstrate potent anti-angiogenic, and selective JAK3/STAT3 down-regulating anticancer characteristics of DX8, a new dexamethasone-based antitumor molecule.
GLUCOCORTICOID RECEPTOR AGONIST AND IMMUNOCONJUGATES THEREOF
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Paragraph 0094-0095, (2021/08/20)
Provided herein are glucocorticoid receptor agonist immunoconjugates, glucocorticoid receptor agonists, pharmaceutical compositiosn including the same, and methods of using the same.
METHODS TO INDUCE TARGETED PROTEIN DEGRADATION THROUGH BIFUNCTIONAL MOLECULES
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Page/Page column 293, (2017/02/28)
The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to nucleic acids, polypeptides, cells, and methods for highly regulated, targeted degradation of proteins through the use of the bifunctional compounds.
