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Cambridge, MA, United States

Terrett N.K.,Ensemble Therapeutics Corporation
Drug Discovery Today: Technologies | Year: 2010

Macrocycles are found widely in nature where they fulfill numerous specific functions. However they have been generally underexploited as drug molecules, as they are larger than more conventional 'Rule of 5' compliant molecules and their synthesis and screening has been considered a challenge. Consequently most pharmaceutical companies have very few macrocycles in their screening files, and yet these compounds can have potent and selective pharmacological activity, and exhibit drug-like properties such as cell membrane permeability and oral bioavailability. To permit the further investigation of macrocyclic drugs, several groups have developed diverse methods for the rapid synthesis and screening of macrocyclic libraries. © 2010 Elsevier Ltd.


Patent
Ensemble Therapeutics Corporation | Date: 2013-02-01

The invention relates generally to macrocyclic compounds of formula I and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of IL-17 and/or are useful in the treatment of medical conditions, such as inflammatory diseases and other IL-17-associated disorders.


Patent
Ensemble Therapeutics Corporation and Bristol Myers Squibb | Date: 2013-11-07

There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.


Zhang Y.,Bristol Myers Squibb | Seigal B.A.,Ensemble Therapeutics Corporation | Terrett N.K.,Ensemble Therapeutics Corporation | Talbott R.L.,Bristol Myers Squibb | And 16 more authors.
ACS Medicinal Chemistry Letters | Year: 2015

A series of dimeric macrocyclic compounds were prepared and evaluated as antagonists for inhibitor of apoptosis proteins. The most potent analogue 11, which binds to XIAP and c-IAP proteins with high affinity and induces caspase-3 activation and ultimately cell apoptosis, inhibits growth of human melanoma and colorectal cell lines at low nanomolar concentrations. Furthermore, compound 11 demonstrated significant antitumor activity in the A875 human melanoma xenograft model at doses as low as 2 mg/kg on a q3d schedule. © 2015 American Chemical Society.


Connors W.H.,Ensemble Therapeutics Corporation | Hale S.P.,Ensemble Therapeutics Corporation | Terrett N.K.,Ensemble Therapeutics Corporation
Current Opinion in Chemical Biology | Year: 2015

Conformationally constrained macrocyclic molecules can present functionally diverse chemical groups distributed over a relatively large molecular surface. This class of molecule is well suited to bind to the extended interface surfaces typical of protein-protein interactions that make up key therapeutically relevant pathways. Large numbers of macrocycles can be generated using DNA-encoded technologies to yield chemically diverse libraries where individual macrocycles are identifiable by a unique covalently attached DNA sequence. Recent developments in this field have revealed library-generated macrocycles possessing potent affinity against tough targets such as XIAP, IL17 and IDE. This review highlights recent progression toward developing drug-like macrocycles and as illustration, advances against these targets. © 2015 Elsevier Ltd.

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