Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 5 of 5

Full-Text Articles in Medicine and Health Sciences

Mithramycin And Analogs For Overcoming Cisplatin Resistance In Ovarian Cancer, David Schweer, J. Robert Mccorkle, Jurgen Rohr, Oleg V. Tsodikov, Frederick R. Ueland, Jill M. Kolesar Jan 2021

Mithramycin And Analogs For Overcoming Cisplatin Resistance In Ovarian Cancer, David Schweer, J. Robert Mccorkle, Jurgen Rohr, Oleg V. Tsodikov, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, …


Structures Of Mithramycin Analogues Bound To Dna And Implications For Targeting Transcription Factor Fli1, Caixia Hou, Stevi Weidenbach, Kristin E. Cano, Zhonghua Wang, Prithiba Mitra, Dmitri N. Ivanov, Jürgen Rohr, Oleg V. Tsodikov Oct 2016

Structures Of Mithramycin Analogues Bound To Dna And Implications For Targeting Transcription Factor Fli1, Caixia Hou, Stevi Weidenbach, Kristin E. Cano, Zhonghua Wang, Prithiba Mitra, Dmitri N. Ivanov, Jürgen Rohr, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Publications

Transcription factors have been considered undruggable, but this paradigm has been recently challenged. DNA binding natural product mithramycin (MTM) is a potent antagonist of oncogenic transcription factor EWS–FLI1. Structural details of MTM recognition of DNA, including the FLI1 binding sequence GGA(A/T), are needed to understand how MTM interferes with EWS–FLI1. We report a crystal structure of an MTM analogue MTM SA–Trp bound to a DNA oligomer containing a site GGCC, and two structures of a novel analogue MTM SA–Phe in complex with DNA. MTM SA–Phe is bound to sites AGGG and GGGT on one DNA, and to AGGG and GGGA(T) …


Semi-Synthetic Mithramycin Derivatives With Anti-Cancer Activity, Jürgen Rohr, Daniel Scott, Markos Leggas, Jhong-Min Chen, Oleg V. Tsodikov Sep 2016

Semi-Synthetic Mithramycin Derivatives With Anti-Cancer Activity, Jürgen Rohr, Daniel Scott, Markos Leggas, Jhong-Min Chen, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Patents

Mithramycin derivatives and their pharmaceutically acceptable salts are disclosed. The mithramycin derivatives can be used in the treatment of Ewing sarcoma or other cancer or neuro-disease associated with an aberrant erythroblast transformation- specific transcription factor.


Glycosylate Derivatives Of Mithramycin, Method Of Preparation And Uses Thereof, Jürgen Rohr, Irfan Baig, Jose Antonio Salas Fernandez, Alfredo Fernandez Brana, Maria Perez Solares Apr 2013

Glycosylate Derivatives Of Mithramycin, Method Of Preparation And Uses Thereof, Jürgen Rohr, Irfan Baig, Jose Antonio Salas Fernandez, Alfredo Fernandez Brana, Maria Perez Solares

Pharmaceutical Sciences Faculty Patents

The present invention provides compounds characterized by the formula (I), where each of the substituent radicals is described in the specification. The invention also describes the use of said compounds in the treatment of various diseases, including: cancer or tumoral processes in general, Paget's disease, hypercalcaemia, hypercalciuria and neurological diseases (inter alia, Parkinson's, Alzheimer's, Huntington's).


Derivatives Of Mithramycin And Methods Of Making And Uses Thereof, Jürgen Rohr, Lily L. Remsing, Mohammad Ner-E-Alam, Jose A. Salas, Carmen Mendez, Alfredo F. Brana, Ana M. Gonzalez Sep 2008

Derivatives Of Mithramycin And Methods Of Making And Uses Thereof, Jürgen Rohr, Lily L. Remsing, Mohammad Ner-E-Alam, Jose A. Salas, Carmen Mendez, Alfredo F. Brana, Ana M. Gonzalez

Pharmaceutical Sciences Faculty Patents

The invention, in one aspect, generally relates to mithramycin derivatives from mutated Streptomyces argillaceus and their production. The invention also relates using the derivatives for the treatment of various diseases. Finally, the invention relates to a mutated Streptomyces argillaceus useful in the production of the mithramycin derivatives.