“Picolog,” a Synthetically-Available Bryostatin Analog, Inhibits Growth of MYC-Induced Lymphoma In Vivo
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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
Paul A. Wender Ph.D., email:
Dean W. Felsher, email:
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.
Brian A. DeChristopher
Alice C. Fan
Dean W. Felsher
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Paul A. Wender
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