Delving into the Latest Updates on GPX-160 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Doxorubicin analog(Gem pharmaceuticals/Boise state University)

Target

DNA x Top II

Mechanism

DNA inhibitors(DNA inhibitors), Top II inhibitors(Topoisomerase II inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Sarcoma

Inactive Indication-

Originator Organization

Gem Pharmaceuticals LLC

Active Organization

Gem Pharmaceuticals LLC

Boise State University

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

This study investigates the effects of daunorubicin, 4-demethoxy-daunorubicin, 11-deoxydaunorubicin, 5-imino-daunorubicin, doxorubicin, 4'-epidoxorubicin and the new derivative 4'-iodo-4'-deoxydoxorubicin, on superoxide anion production in heart sarcosomes and by mitochondrial NADH dehydrogenase. In cardiac sarcosomes all the anthracyclines tested enhanced NADPH-dependent superoxide formation which followed Michaelis-Menten kinetics and their Vmax were similar to that of doxorubicin except 5-iminodaunorubicin which did not affect superoxide production and 4'-iodo-4'-deoxydoxorubicin which showed significantly lower Vmax and Km. The superoxide formation by NADH dehydrogenase in the presence of anthracyclines appeared to follow saturation kinetics, depending by NADH. 4-Demethoxydaunorubicin and 4'-epidoxorubicin showed Vmax higher than that of doxorubicin although the Km values were similar. By contrast 5-iminodaunorubicin failed to increase superoxide production over control levels and 4'-Iodo-4'-deoxydoxorubicin hardly enhanced superoxide production by NADH dehydrogenase. A marked difference of superoxide formation rate was shown for the molecules tested in our in vitro system. The behaviour displayed in vitro by the imino- and iodo-derivatives well correlate to their moderate cardiotoxicity in vivo. For the other molecules tested, the poor correlation between the in vitro production of superoxides and the in vivo cardiotoxicity degree might depend on the pharmacokinetic steps which may modify the cardiac effects of these anthracyclines.

100 Deals associated with GPX-160

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