“Picolog,” a Synthetically-Available Bryostatin Analog, Inhibits Growth of MYC-Induced LymphomaIn Vivo
Year: 2012
Type: article
Abstract: Brian A. DeChristopher 1,* , Alice C. Fan 2,* , Dean W. Felsher 2 , Paul A. Wender 1 1 Departments of Chemistry and Chemical and Systems Biology, Stanford University, Stanford, CA 94305-5080 2 Division of Oncology, Stanford University School of Medicine, Stanford, CA 94305 * Denotes equal contribution Received: January 22, 2012; Accepted: February 2, 2012; Published: February 2, 2012; Keywords: bryostatin, picolog, lymphoma, PKC Correspondence: Paul A. Wender Ph.D., email: // Dean W. Felsher, email: // // Abstract Bryostatin 1 is a naturally occurring complex macrolide with potent anti-neoplastic activity. However, its extremely low natural occurrence has impeded clinical advancement. We developed a strategy directed at the design of simplified and synthetically more accessible bryostatin analogs. Our lead analog, “picolog”, can be step-economically produced. Picolog, compared to bryostatin, exhibited superior growth inhibition of MYC-induced lymphoma in vitro . A key mechanism of picolog’s (and bryostatin’s) activity is activation of PKC. A novel nano-immunoassay (NIA) revealed that picolog treatment increased phospho-MEK2 in the PKC pathway. Moreover, the inhibition of PKC abrogated picolog’s activity. Finally, picolog was highly potent at 100 micrograms/kg and well tolerated at doses ranging from 100 micrograms/kg to 1 milligram/kg in vivo for the treatment of our aggressive model of MYC-induced lymphoma. We provide the first in vivo validation that the bryostatin analog, picolog, is a potential therapeutic agent for the treatment of cancer and other diseases.
Source: Oncotarget
Institutions: Stanford University, Stanford Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G1121106320, In Vivo Cellular and Molecular Imaging Center@Stanford, Molecular and Cellular Basis of Oncogene Addiction, Nanoscale analysis of proteomic response to novel targeted therapies for lymphoma, Synthetic Studies Related to Cancer Research/Treatment, Computational Modeling of Cancer Biology, G4821107225, Clinical and Laboratory Studies of Malignant Lymphomas, G563173265, G5969126648, MYC's Role in the Initiation and Maintenance of Cancer, G8238088159, G9000323393, Synthetic Studies Related to Cancer Research/Treatment
OpenAlex ID: W1541535305