Michael D. Levin
University of Utah
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Publication
Featured researches published by Michael D. Levin.
Journal of the American Chemical Society | 2013
Ramin Dubey; Michael D. Levin; Lajos Szabo; Csaba Laszlo; Swati Kushal; Jason B. Singh; Philip Oh; Jan E. Schnitzer; Bogdan Olenyuk
Hypoxia is a hallmark of solid tumors, is associated with local invasion, metastatic spread, resistance to chemo- and radiotherapy, and is an independent, negative prognostic factor for a diverse range of malignant neoplasms. The cellular response to hypoxia is primarily mediated by a family of transcription factors, among which hypoxia-inducible factor 1 (HIF1) plays a major role. Under normoxia, the oxygen-sensitive α subunit of HIF1 is rapidly and constitutively degraded but is stabilized and accumulates under hypoxia. Upon nuclear translocation, HIF1 controls the expression of over 100 genes involved in angiogenesis, altered energy metabolism, antiapoptotic, and pro-proliferative mechanisms that promote tumor growth. A designed transcriptional antagonist, dimeric epidithiodiketopiperazine (ETP 2), selectively disrupts the interaction of HIF1α with p300/CBP coactivators and downregulates the expression of hypoxia-inducible genes. ETP 2 was synthesized via a novel homo-oxidative coupling of the aliphatic primary carbons of the dithioacetal precursor. It effectively inhibits HIF1-induced activation of VEGFA, LOX, Glut1, and c-Met genes in a panel of cell lines representing breast and lung cancers. We observed an outstanding antitumor efficacy of both (±)-ETP 2 and meso-ETP 2 in a fully established breast carcinoma model by intravital microscopy. Treatment with either form of ETP 2 (1 mg/kg) resulted in a rapid regression of tumor growth that lasted for up to 14 days. These results suggest that inhibition of HIF1 transcriptional activity by designed dimeric ETPs could offer an innovative approach to cancer therapy with the potential to overcome hypoxia-induced tumor growth and resistance.
Bioconjugate Chemistry | 2015
Ramin Dubey; Swati Kushal; Alexis Mollard; Lesya Vojtovich; Philip Oh; Michael D. Levin; Jan E. Schnitzer; Ilya Zharov; Bogdan Olenyuk
We report in vitro and in vivo evaluation of a newly designed trifunctional theranostic agent for targeting solid tumors. This agent combines a dendritic wedge with high boron content for boron neutron capture therapy or boron MRI, a monomethine cyanine dye for visible-light fluorescent imaging, and an integrin ligand for efficient tumor targeting. We report photophysical properties of the new agent, its cellular uptake and in vitro targeting properties. Using live animal imaging and intravital microscopy (IVM) techniques, we observed a rapid accumulation of the agent and its retention for a prolonged period of time (up to 7 days) in fully established animal models of human melanoma and murine mammary adenocarcinoma. This macromolecular theranostic agent can be used for targeted delivery of high boron load into solid tumors for future applications in boron neutron capture therapy.
Journal of the American Chemical Society | 1999
Bogdan Olenyuk; Michael D. Levin; Jeffery A. Whiteford; Jeffrey E. Shield; Peter J. Stang
Journal of the American Chemical Society | 1999
Jim Fan; Jeffery A. Whiteford; Bogdan Olenyuk; Michael D. Levin; Peter J. Stang; Everly B. Fleischer
Chemical Reviews | 2000
Michael D. Levin; and Piotr Kaszynski; Josef Michl
Journal of the American Chemical Society | 2000
Michael D. Levin; Peter J. Stang
Journal of the American Chemical Society | 2001
Alexander B. Shtarev; Evgueni Pinkhassik; Michael D. Levin; and Ivan Stibor; Josef Michl
Journal of the American Chemical Society | 1997
Michael D. Levin; Steven J. Hamrock; Piotr Kaszynski; Alexander B. Shtarev; Galina A. Levina; Bruce C. Noll; Martin E. Ashley; R. A. Newmark; George G. I. Moore; Josef Michl
Journal of Organic Chemistry | 1999
William Adcock; Andrei V. Blokhin; Gordon M. Elsey; Nicholas H. Head; Alexander R. Krstic; Michael D. Levin; Josef Michl; Jamie Munton; Evgueni Pinkhassik; Marc Robert; Jean-Michel Savéant; and Alexander Shtarev; Ivan Stibor
Chemistry-an Asian Journal | 2007
Masahiro Ehara; Hiroshi Nakatsuji; Donald E. David; Evgueni Pinkhassik; Michael D. Levin; Marcin Apostol; Josef Michl