Gary Olson - Academia.edu (original) (raw)
Papers by Gary Olson
Woods et al., JACS, 68,2483 (1946). Konowal et al., Rocz. Chem, 42, 2045 (1966). Jurczak et al., ... more Woods et al., JACS, 68,2483 (1946). Konowal et al., Rocz. Chem, 42, 2045 (1966). Jurczak et al., Rocz. Chem., 44, 1587 (1970). Chmielewski et al., Rocz. Chem., 46, 627 (1972). Zwierzchowska-Nowakowska et al., Rocz. Chem, 48, 1929 (1974). Makin, Russ. Chem. Rev., 38, 237 (1969). Shavrygina et al., J. Org. Chem., USSR, 2, 1349 (1966). Pommer, Angew. Chem, 72,811 (1960). Primary Examiner-Nicky Chan Attorney, Agent, or Firm-Jon S. Saxe; Bernard S. Leon; George W. Johnston
Journal of Clinical Oncology
e23161Background: We previously screened for small molecules that could stimulate anti-tumor immu... more e23161Background: We previously screened for small molecules that could stimulate anti-tumor immunity within tumor cells through p53-independent TRAIL upregulation. TRAIL initiates apoptosis select...
Cell cycle (Georgetown, Tex.), Jan 10, 2017
Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a ... more Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene activation. ONC201 is under investigation in multiple clinical trials to treat patients with cancer. Given the unique imipridone core chemical structure of ONC201, we synthesized a series of analogues to identify additional compounds with distinct therapeutic properties. Several imipridones with a broad range of in vitro potencies were identified in an exploration of chemical derivatives. Based on in vitro potency in human cancer cell lines and lack of toxicity to normal human fibroblasts, imipridones ONC206 and ONC212 were prioritized for further study. Both analogues inhibited colony formation, and induced apoptosis and downstream signaling that involves the integrated stress response and Akt/ERK, similar to ONC201. Compared to ONC201, ONC206 demonstrated improved inhibition of cell migration while ONC212 exhibited rapid kinetics of ac...
Oncotarget, 2016
ONC201 is the founding member of a novel class of anti-cancer compounds called imipridones that i... more ONC201 is the founding member of a novel class of anti-cancer compounds called imipridones that is currently in Phase II clinical trials in multiple advanced cancers. Since the discovery of ONC201 as a p53-independent inducer of TRAIL gene transcription, preclinical studies have determined that ONC201 has anti-proliferative and pro-apoptotic effects against a broad range of tumor cells but not normal cells. The mechanism of action of ONC201 involves engagement of PERK-independent activation of the integrated stress response, leading to tumor upregulation of DR5 and dual Akt/ERK inactivation, and consequent Foxo3a activation leading to upregulation of the death ligand TRAIL. ONC201 is orally active with infrequent dosing in animals models, causes sustained pharmacodynamic effects, and is not genotoxic. The first-in-human clinical trial of ONC201 in advanced aggressive refractory solid tumors confirmed that ONC201 is exceptionally well-tolerated and established the recommended phase I...
Woods et al., JACS, 68,2483 (1946). Konowal et al., Rocz. Chem, 42, 2045 (1966). Jurczak et al., ... more Woods et al., JACS, 68,2483 (1946). Konowal et al., Rocz. Chem, 42, 2045 (1966). Jurczak et al., Rocz. Chem., 44, 1587 (1970). Chmielewski et al., Rocz. Chem., 46, 627 (1972). Zwierzchowska-Nowakowska et al., Rocz. Chem, 48, 1929 (1974). Makin, Russ. Chem. Rev., 38, 237 (1969). Shavrygina et al., J. Org. Chem., USSR, 2, 1349 (1966). Pommer, Angew. Chem, 72,811 (1960). Primary Examiner-Nicky Chan Attorney, Agent, or Firm-Jon S. Saxe; Bernard S. Leon; George W. Johnston
Journal of Clinical Oncology
e23161Background: We previously screened for small molecules that could stimulate anti-tumor immu... more e23161Background: We previously screened for small molecules that could stimulate anti-tumor immunity within tumor cells through p53-independent TRAIL upregulation. TRAIL initiates apoptosis select...
Cell cycle (Georgetown, Tex.), Jan 10, 2017
Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a ... more Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene activation. ONC201 is under investigation in multiple clinical trials to treat patients with cancer. Given the unique imipridone core chemical structure of ONC201, we synthesized a series of analogues to identify additional compounds with distinct therapeutic properties. Several imipridones with a broad range of in vitro potencies were identified in an exploration of chemical derivatives. Based on in vitro potency in human cancer cell lines and lack of toxicity to normal human fibroblasts, imipridones ONC206 and ONC212 were prioritized for further study. Both analogues inhibited colony formation, and induced apoptosis and downstream signaling that involves the integrated stress response and Akt/ERK, similar to ONC201. Compared to ONC201, ONC206 demonstrated improved inhibition of cell migration while ONC212 exhibited rapid kinetics of ac...
Oncotarget, 2016
ONC201 is the founding member of a novel class of anti-cancer compounds called imipridones that i... more ONC201 is the founding member of a novel class of anti-cancer compounds called imipridones that is currently in Phase II clinical trials in multiple advanced cancers. Since the discovery of ONC201 as a p53-independent inducer of TRAIL gene transcription, preclinical studies have determined that ONC201 has anti-proliferative and pro-apoptotic effects against a broad range of tumor cells but not normal cells. The mechanism of action of ONC201 involves engagement of PERK-independent activation of the integrated stress response, leading to tumor upregulation of DR5 and dual Akt/ERK inactivation, and consequent Foxo3a activation leading to upregulation of the death ligand TRAIL. ONC201 is orally active with infrequent dosing in animals models, causes sustained pharmacodynamic effects, and is not genotoxic. The first-in-human clinical trial of ONC201 in advanced aggressive refractory solid tumors confirmed that ONC201 is exceptionally well-tolerated and established the recommended phase I...