Kudos Pharmaceuticals Limited

Cancer Research Campaign Technology Limited

Maybridge Limited

Institute of Cancer Research: Royal Cancer Hospital (the)

Duke University

The Institute of Cancer Research: Royal Cancer Hospital

The Institute of Cancer Research

Kudo Pharmaceuticals Limited

Alan Ashworth

Keith Allan Menear

Niall Morrison Barr Martin

Christopher Lord

Dan Niculescu-Duvaz

Graeme Cameron Murray Smith

Stephen Philip Jackson

Graeme Cameron Smith

Xiao-Ling Fan Cockcroft

Frank Kerrigan

Ian Timothy Williams Matthews

Vincent Junior M Loh

Trevor Robert Perrior

Rebekah Elisabeth Key

Niall Martin

Ashley Nicholas Jarvis

Stuart Firth-Clark

Melanie Jayne Bayford

Raymond John Boffey

Roderick Alan Porter

Rehan Aqil

Mark O'Connor

Anna Hopkins

Keith Robert Willison

Michael Rudolf Stratton

Christopher James Lord

Christopher John Marshall

David Anthony Hughes

Philip Alan Skone

Richard Francis Wooster

Phillip Andrew Futreal

Richard James Rowland Elliott

Hiroshi Kubota

Richard James Rowland Elliot

Niall Morrison Martin

Vincent M Loh

Jessica Frankum

Rachel Brough

Roderick Porter

Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRor CRR; if X&#x2550;NRthen n is 1 or 2 and if X&#x2550;CRRthen n is 1; Ris selected from the group consisting of H, optionally substituted Calkyl, Caryl, Cheterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; Ris selected from H, hydroxy, amino; or Rand Rmay together form a spiro-Ccycloalkyl or heterocyclyl group; Rand Rare both hydrogen, or when X is CRR, R, R, Rand R, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and Ris selected from H and halo.

Phthalazinone derivatives

Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRor CRR; if X&#x2550;NRthen n is 1 or 2 and if X&#x2550;CRRthen n is 1; Ris selected from the group consisting of H, optionally substituted Calkyl, Caryl, Cheterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; Ris selected from H, hydroxy, amino; or Rand Rmay together form a spiro-Ccycloalkyl or heterocyclyl group; Rand Rare both hydrogen, or when X is CRR, R, R, Rand R, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; andRis selected from H and halo.

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted-2/-/-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc. 

3-aryl-5-substituted-isoquinolin-1-one compounds and their therapeutic use

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted-2H-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc. 

Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRor CRR; if X&#x2550;NRthen n is 1 or 2 and if X&#x2550;CRRthen n is 1; Ris selected from the group consisting of H, optionally substituted Calkyl, Caryl, Cheterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; Ris selected from H, hydroxy, amino; or Rand Rmay together form a spiro-Ccycloalkyl or heterocyclyl group; Rand Rare both hydrogen, or when X is CRR, R, R, Rand R, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and

The present invention relates to the recognition that inhibition of the base excision repair pathway is selectively lethal in cells which are deficient in HR dependent DNA DSB repair. Methods and means relating to the treatment of cancers which are deficient in HR dependent DNA DSB repair using inhibitors which target base excision repair components, such as PARP, is provided herein.

DNA damage repair inhibitors for treatment of cancer

DNA damage repair inhibitors for the treatment of cancer

Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRor CRR; if X=NRthen n is 1 or 2 and if X=CRRthen n is 1; Ris selected from the group consisting of H, optionally substituted Calkyl, Caryl, Cheterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; Ris selected from H, hydroxy, amino; or Rand Rmay together form a spiro-Ccycloalkyl or heterocyclyl group; Rand Rare both hydrogen, or when X is CRR, R, R, Rand R, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and Ris selected from H and halo.

Nucleic acid encoding subunits of a polypeptide folding complex containing TCp-1 is useful in expression of the subunits for assembly of the complex in vitro or in vivo. The complex promotes folding of polypeptides, such as tubulin, e.g., following recombinant expression. The sequences share a high degree of homology but the C-termini are sufficiently different to enable peptides with sequences derived therefrom to be used in obtaining antibodies specific for the various subunits, i.e., able to distinguish between them. The antibodies may be used in analysis and design of complexes able to fold different polypeptides.

Folding protein complexes

The identification and sequencing of the BRCA2 gene is disclosed as well as the amino acid sequence of the corresponding BRCA2 polypeptides. BRCA2 alleles including those with mutations in the BRCA2 gene which are associated with a predisposition to develop cancer, especially breast and ovarian cancer are also disclosed. The present invention further relates to polypeptides encoded by the above nucleic acid. The present invention further relates to uses of much BRCA2 nucleic acid and BRCA2 polypeptides, in particular in the diagnostic, prognostic or therapeutic treatment of cancer.

Materials and methods relating to the identification and sequencing of

Methods for screening of substances for therapeutic activity and yeast

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London, United Kingdom

Alan Ashworth