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They are potent modulators of protein kinase C isozymes (PKC\u03b1: ki = 1.3-188 nM), and are one of the most extensively investigated marine natural products in clinical trials. Although ~21 natural bryostatins have been isolated, however only bryostatin-1 (1) has received much interest among medicinal chemists and clinicians. The structure-activity relationship of bryostatins has been well established, with the identification of key pharmacophoric features important for PKC modulation. The low natural abundance and the long synthetic route have prompted medicinal chemists to come-up with simplified analogs. Bryostatin skeleton comprises three pyran rings connected to each other to form a macrocyclic lactone. The simplest analog 27 contains only one pyran, which is also able to modulate the PKC\u03b1 activity; however, the cyclic framework appears to be essential for the desired level of potency. Another simplified analog 17 (\"picolog\") exhibited potent and in-vivo efficacy against lymphoma. Bryostatin-1 (1) has shown an acceptable intravenous pharmacokinetic profile in mice and displayed promising in-vivo efficacy in mice models of various cancers and Alzheimer's disease. Bryostatin-1 was investigated in numerous Phase I\/II oncology clinical trials; it has shown minimal effect as a single agent, however, provided encouraging results in combination with other chemotherapy agents. FDA has granted orphan drug status to bryostatin-1 in combination with paclitaxel for esophageal cancer. Bryostatin-1 has also received orphan drug status for fragile X syndrome. Bryostatin-1 was also investigated in clinical studies for Alzheimer's disease and HIV infection. In a nutshell, the natural as well as synthetic bryostatins have generated a strong hope to emerge as treatment for cancer along with many other diseases.<\/jats:p><\/jats:sec>","DOI":"10.2174\/1568026620666200325110444","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T14:35:51Z","timestamp":1585146951000},"page":"1124-1135","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Preclinical and Clinical Studies on Bryostatins, A Class of Marine-Derived Protein Kinase C Modulators: A Mini-Review"],"prefix":"10.2174","volume":"20","author":[{"given":"Rinky","family":"Raghuvanshi","sequence":"first","affiliation":[{"name":"Medicinal Chemistry Division, CSIR- Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6081-5787","authenticated-orcid":true,"given":"Sandip B.","family":"Bharate","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Division, CSIR- Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"6761","DOI":"10.1021\/cr300410v","volume":"113","author":"Bharate S.B.","year":"2013","unstructured":"Bharate S.B.; Sawant S.D.; Singh P.P.; Vishwakarma R.A.; Kinase inhibitors of marine origin. 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