Medical University of South Carolina

Cyclacel Limited

Senex Biotechnology, Inc.

Cyclacel Limted

Campbell McInnes

Peter Martin Fischer

Shudong Wang

Igor B Roninson

Mengqian Chen

Shu Liu

Jing Li

Li Zhang

Gavin Wood

Christopher Meades

Sandra Navonne Craig

Chad Beneker

Doaa Boshra Farag

Janice O'Boyle

Nicholas James Westwood

Joshua Kyle Bolger

Daniella I Zheleva

Ozgur Sahin

Mark Thomas

Neil McIntyre

Martin J I Andrews

Weng C Chan

Gail E Atkinson

Jiaxin Liang

Abdol-Hossein Rezaeian

Ozge Saatci

Metin Cetin

Padmavathy Nandha Premnath

Disclosed are small molecule PLK inhibitors that can target the polo box domain (PBD). Inhibitors can have an atomic mass of about 1000 Da or less and a general structure of For instance, the inhibitors can include an alkyl benzamido benzoic acid core structure.

Small molecule inhibitors selective for polo-like kinase protein

Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted quinoline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.

Quinoline-based compounds and methods of inhibiting CDK8/19

Described herein are novel compounds that block the activity of LOX family members having good IC50 values, no cellular toxicity below 10 &#x3bc;M, induce sensitization of the cells to doxorubicin, strong activity in a recombinant LOX/LOXL2 activity, and a chemical structure that is drug-like and does not have a PAINS flag, as well as, methods of treatment using the compounds with respect to cancer, organ fibrosis, neurodegenerative and cardiovascular diseases.

Inhibitors of lysyl oxidases

Small molecule inhibitors selective for polo-like kinase proteins

Disclosed herein are bicyclic pyridines, such as thienopyridine, pyrrolopyridine, furopyridine compounds, and methods for treating cancers.

Bicyclic pyridine compositions and methods of using the same for cancer therapy

Herein are described peptide-based compositions for modifying Raf kinase protein Dimerization. These compositions, treatments, and methods of use are directed to peptides that display a binding affinity for the dimer interface of a Raf kinase protein, methods for modifying Raf kinase dimerization, and methods for inhibiting tumor growth. An embodiment of the disclosure is a peptide generated by modifying an ordered sequence chosen from SEQ ID NO: 1 which corresponds to amino acids 503-521 of B-Raf kinase. The peptides disclosed herein include a modification to an ordered sequence of amino acids derived from SEQ ID NO: 1 that can improve or otherwise alter binding affinity of the peptide to the dimer interface.

Peptide based inhibitors of Raf kinase protein dimerization and kinase activity

Methods for developing non-peptidic inhibitors that target the polo-box domain of PLK1 proteins are described. Methods include developing structure activity relationships for peptidic inhibitors followed by development of non-peptide fragment alternatives for portions of the peptide inhibitors. The non-peptide fragment can provide similar structure activity relationship as the replaced peptide. Fragment alternatives to key binding determinants are identified in an iterative computational and synthetic process facilitated through understanding of the peptide structure-activity relationships. The approach is informed by peptide structure-activity data obtained through synthesis and testing of truncated and mutated analogs of known PBD binding motifs.

Fragment ligated inhibitors selective for the polo box domain of PLK1

Structural and functional analysis of peptide inhibitor binding to the cyclin D and cyclin A groove has been investigated and used to design peptides that provide the basis for structure-activity relationships, have improved binding and have potential for development as chemical biology probes, as potential diagnostics and as therapeutics in the treatment of proliferative diseases including cancer and inflammation.

Cyclin based inhibitors of CDK2 and CDK4

Structural and functional analysis of peptide inhibitor binding to the cyclin D1 groove has been investigated and used to design peptides that provide the basis for structure-activity relationships, have improved binding and have potential for development as chemical biology probes, as potential diagnostics and as therapeutics in the treatment of proliferative diseases including cancer and inflammation.

The present invention relates to substituted pyrimidines of formula I, their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependent kinases (CDKs) and hence their use in the treatment of proliferative disorders and/or viral disorders. 

Pyrimidine compounds

A compound of formula 1, or a pharmaceutically acceptable salt thereof, wherein: X is S, O, or NH; 'a' is a single bond; or 'a' is a double bond and one of Rand R, and one of Rand Rare absent; Ris H; or is selected from an alkyl group, a cycloalkyl group, a heteroaryl group, an aralkyl group, CO-alkyl, SO-alkyl, CORand an aryl group, each of which optionally contains one or more heteroatoms, and is optionally substituted with one or more groups selected from Rand R; Ris H, R, or an alkyl group optionally substituted with one or more Rgroups; R, R, R, and Rare each independently selected from H, R, an alkyl group and an alkenyl group, wherein said alkyl and alkenyl groups are optionally substituted with one or more Rgroups; or Rand R, and/or Rand Rtogether represent &#x2550;O; Ris H, R, NH(CH)R, CO(CH)R, NHCO(CH)R, O(CH)R, or an alkyl or phenyl group, each of which is optionally substituted with one or more groups selected from Rand R; Ris OR, NRR, halogen, CF, NO, COR, CN, COOR, CONRR, SORor SONRR; Ris a saturated or unsaturated 5- or 6-membered cyclic group optionally containing one or more heteroatoms selected from N, O and S, and optionally substituted with one or more Rgroups; R, R, Rand Rare each independently H or a hydrocarbyl group; and n is 0, 1, 2 or 3. Further aspects of the invention relate to pharmaceutical compositions comprising compounds of formula 1, and the therapeutic use thereof in the treatment of proliferative disorders, viral disorders, CNS disorders, diabetes, stroke and cardiovascular disorders.

Thiazolo-, oxazalo and imidazolo-quinazoline compounds capable of inhibiting protein kinases

Growing community of inventors

Irmo, SC, United States of America

Campbell McInnes