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So far Circle Pharma has created 33 blog entries.

Circle Pharma Announces Receipt of Seed Funding and Initiation of Two Collaborations

2017-09-25T10:02:04+00:00 September 22nd, 2014|Press Releases|

Circle Pharma, Inc., a newly created, early-stage biotechnology company, today announced that it has received seed funding from Pfizer Inc. and QB3’s seed-stage venture fund, Mission Bay Capital, LLC, and has initiated two collaborations with Pfizer to develop cell permeable macrocyclic peptide therapeutics.

“We are very pleased to have launched Circle with the backing of Pfizer and Mission Bay Capital, and to have initiated two exciting collaborative projects with Pfizer,” said David J. Earp […]

Macrocyclic Drugs and Clinical Candidates: What Can Medicinal Chemists Learn from Their Properties?

2017-09-19T10:49:26+00:00 August 28th, 2013|on Macrocycles, Publications|

by Fabrizio Giordanetto and Jan Kihlberg

Macrocycles are ideal in efforts to tackle “difficult” targets, but our understanding of what makes them cell permeable and orally bioavailable is limited. Analysis of approximately 100 macrocyclic drugs and clinical candidates revealed that macrocycles are predominantly used for infectious disease and in oncology and that most belong to the macrolide or cyclic peptide class. A significant number (N = 34) of these macrocycles are administered […]

Form and function in cyclic peptide natural products: a pharmacokinetic perspective

2017-09-25T12:55:08+00:00 May 21st, 2013|by our Team Members, Publications|

by Bockus AT, McEwen CM, Lokey RS

The structural complexity of many natural products sets them apart from common synthetic drugs, allowing them to access a biological target space that lies beyond the enzyme active sites and receptors targeted by conventional small molecule drugs. Naturally occurring cyclic peptides, in particular, exhibit a wide variety of unusual and potent biological activities. Many of these compounds penetrate cells by passive diffusion and some, like the clinic […]

Macrocycles and Constrained Peptides

2017-09-19T10:50:05+00:00 April 11th, 2013|on Macrocycles, Publications|

Macrocycles and constrained peptides, generally defined as cyclic small molecules or peptides of 500–2,000 Da, have undergone a rebirth over the last five years in drug discovery, due mainly to the introduction of new approaches for their synthesis and screening. This scientific progress has fueled a burst of business activity, with at least 12 biotech companies in the space, of which almost half were founded in the last 5 years.

This special collection from SciBX: Science-Business eXchange p […]

Predicting Efflux Ratios and Blood-Brain Barrier Penetration from Chemical Structure: Combining Passive Permeability with Active Efflux by P-Glycoprotein

2017-09-19T12:09:48+00:00 December 2nd, 2012|by our Team Members, Publications|

by Elena Dolghih and Matthew P. Jacobson

In order to reach their pharmacologic targets, successful central nervous system (CNS) drug candidates have to cross a complex protective barrier separating brain from the blood. Being able to predict a priori which molecules can successfully penetrate this barrier could be of significant value in CNS drug discovery. Herein we report a new computational approach that combines two mechanism-based models, for passive permeation and for active ef […]

Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance

2017-09-25T12:59:45+00:00 October 3rd, 2012|by our Team Members, Publications|

by Rand AC, Leung SS, Eng H, Rotter CJ, Sharma R, Kalgutkar AS, Zhang Y, Varma MV, Farley KA, Khunte B, Limberakis C, Price DA, Liras S, Mathiowetz AM, Jacobson MP, Lokey RS

A series of cyclic peptides were designed and prepared to investigate the physicochemical properties that affect oral bioavailabilty of this chemotype in rats. In particular, the ionization state of the peptide was examined by the incorporation of naturally occurring amino acid residues that are charged in differ […]

Macrocycles in New Drug Discovery

2017-09-19T10:50:41+00:00 August 2nd, 2012|on Macrocycles, Publications|

by Jamie Mallinson and Ian Collins

The use of drug-like macrocycles is emerging as an exciting area of medicinal chemistry, with several recent examples highlighting the favorable changes in biological and physicochemical properties that macrocyclization can afford. Natural product macrocycles and their synthetic derivatives have long been clinically useful and attention is now being focused on the wider use of macrocyclic scaffolds in medicinal chemistry in the search for new drugs […]

Testing physical models of passive membrane permeation

2017-09-25T12:29:15+00:00 June 25th, 2012|by our Team Members, Publications|

by Leung SS, Mijalkovic J, Borrelli K, Jacobson MP

The biophysical basis of passive membrane permeability is well-understood, but most methods for predicting membrane permeability in the context of drug design are based on statistical relationships that indirectly capture the key physical aspects. Here, we investigate molecular mechanics-based models of passive membrane permeability and evaluate their performance against different types of experimental data, including parallel artifi […]

Predicting and improving the membrane permeability of peptidic small molecules

2017-09-25T12:30:26+00:00 April 12th, 2012|by our Team Members, Publications|

by Rafi SB, Hearn BR, Vedantham P, Jacobson MP, Renslo AR

We evaluate experimentally and computationally the membrane permeability of matched sets of peptidic small molecules bearing natural or bioisosteric unnatural amino acids. We find that the intentional introduction of hydrogen bond acceptor-donor pairs in such molecules can improve membrane permeability while retaining or improving other favorable drug-like properties. We employ an all-atom force field based method to calculate […]

On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds

2017-09-25T12:31:12+00:00 September 25th, 2011|by our Team Members, Publications|

by White TR, Renzelman CM, Rand AC, Rezai T, McEwen CM, Gelev VM, Turner RA, Linington RG, Leung SS, Kalgutkar AS, Bauman JN, Zhang Y, Liras S, Price DA, Mathiowetz AM, Jacobson MP, Lokey RS

Backbone N-methylation is common among peptide natural products and has a substantial impact on both the physical properties and the conformational states of cyclic peptides. However, the specific impact of N-methylation on passive membrane diffusion in cyclic peptides has not been investigated s […]