Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Michael D. Levin is active.

Publication


Featured researches published by Michael D. Levin.


Journal of the American Chemical Society | 2013

Suppression of tumor growth by designed dimeric epidithiodiketopiperazine targeting hypoxia-inducible transcription factor complex.

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

Tumor targeting, trifunctional dendritic wedge.

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

Self-Assembly of Nanoscopic Dodecahedra from 50 Predesigned Components

Bogdan Olenyuk; Michael D. Levin; Jeffery A. Whiteford; Jeffrey E. Shield; Peter J. Stang


Journal of the American Chemical Society | 1999

Self-Assembly of Porphyrin Arrays via Coordination to Transition Metal Bisphosphine Complexes and the Unique Spectral Properties of the Product Metallacyclic Ensembles

Jim Fan; Jeffery A. Whiteford; Bogdan Olenyuk; Michael D. Levin; Peter J. Stang; Everly B. Fleischer


Chemical Reviews | 2000

Bicyclo[1.1.1]pentanes, [n]Staffanes, [1.1.1]Propellanes, and Tricyclo[2.1.0.02,5]pentanes

Michael D. Levin; and Piotr Kaszynski; Josef Michl


Journal of the American Chemical Society | 2000

Insights into the mechanism of coordination-directed self-assembly [22]

Michael D. Levin; Peter J. Stang


Journal of the American Chemical Society | 2001

Partially Bridge-Fluorinated Dimethyl Bicyclo[1.1.1]pentane-1,3-dicarboxylates: Preparation and NMR Spectra

Alexander B. Shtarev; Evgueni Pinkhassik; Michael D. Levin; and Ivan Stibor; Josef Michl


Journal of the American Chemical Society | 1997

Preparation, Structure, and Properties of Symmetrically 1,3-Difunctionalized Penta- and Hexafluorobicyclo[1.1.1]pentanes

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

Manifestations of Bridgehead-Bridgehead Interactions in the Bicyclo(1.1.1)pentane Ring System

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

Coupling between Substituents as a Function of Cage Structure: Synthesis and Valence Ionized States of Bridgehead Disubstituted Parent and Hexafluorinated Bicyclo[1.1.1]pentane Derivatives C5X6Y2

Masahiro Ehara; Hiroshi Nakatsuji; Donald E. David; Evgueni Pinkhassik; Michael D. Levin; Marcin Apostol; Josef Michl

Collaboration


Dive into the Michael D. Levin's collaboration.

Top Co-Authors

Avatar

Josef Michl

University of Colorado Boulder

View shared research outputs
Top Co-Authors

Avatar

Bogdan Olenyuk

University of Southern California

View shared research outputs
Top Co-Authors

Avatar

Evgueni Pinkhassik

University of Colorado Boulder

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Swati Kushal

University of Southern California

View shared research outputs
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge