Delving into the Latest Updates on Silvestrol Analogues(compounds 74 ) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target-

Action

inhibitors

Mechanism

Protein synthesis inhibitors

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

Neoplasms

Originator Organization

Infinity Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Infinity Pharmaceuticals, Inc.

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Author: Helble, Joseph ; Ali, Janid ; West, Kip ; Bahadoor, Adilah ; Douglas, Mark ; Conley, James ; Tillotson, Bonnie ; Smith, Sherri ; Lescarbeau, André ; Fritz, Christian ; McGovern, Karen ; Belani, Jitendra ; O’Hearn, Patrick ; Nair, Somarajan J. ; Slocum, Kelly ; Wylie, Andrew ; Tremblay, Martin R. ; Liu, Tao ; Castro, Alfredo C. ; Peluso, Stéphane ; Palombella, Vito J.

Misregulation of protein translation plays a critical role in human cancer pathogenesis at many levels. Silvestrol, a cyclopenta[b]benzofuran natural product, blocks translation at the initiation step by interfering with assembly of the eIF4F translation complex. Silvestrol has a complex chemical structure whose functional group requirements have not been systematically investigated. Moreover, silvestrol has limited development potential due to poor druglike properties. Herein, we sought to develop a practical synthesis of key intermediates of silvestrol and explore structure-activity relationships around the C6 position. The ability of silvestrol and analogues to selectively inhibit the translation of proteins with high requirement on the translation-initiation machinery (i.e., complex 5'-untranslated region UTR) relative to simple 5'UTR was determined by a cellular reporter assay. Simplified analogues of silvestrol such as compounds 74 and 76 were shown to have similar cytotoxic potency and better ADME characteristics relative to those of silvestrol.

100 Deals associated with Silvestrol Analogues(compounds 74 )

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