Kudos Pharmaceuticals Limited

Cambridge Enterprise Limited

Maybridge Limited

Centre National De La Recherche Scientifique

The Institute of Cancer Research: Royal Cancer Hospital

Mission Therapeutics Limited

The Institute of Cancer Research

Kudo Pharmaceuticals Limited

Stephen Philip Jackson

Alan Ashworth

Graeme Cameron Smith

Keith Allan Menear

Niall Morrison Barr Martin

Xiao-Ling Fan Cockcroft

Ian Timothy Williams Matthews

Frank Kerrigan

Vincent Junior M Loh

Graeme Cameron Murray Smith

Mark O'Connor

Niall Martin

Roger John Griffin

Laurent Jean Martin Rigoreau

Ian Timothy Matthews

Xavier Jacq

Helen Robinson

Aidan Doherty

Yaara Ofir-Rosenfeld

Marina Della

Paul Wijnhoven

Geoffrey Weller

Ryotaro Nishi

Nicholas David Lakin

Alan Yin Kai Lau

Delphine Laurence Daniele Larrieu

David A Gell

Susan Elizabeth Critchlow

Raphaël Joël Rodriguez

Marc Geoffery Hummersone

Sébastien Frédéric Stéphane Britton

Jessica Anne Downs

Niall Morrison Martin

Vincent M Loh

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

The present application relates to materials and methods for exploiting synthetic lethality and/or chemo-sensitisation in DNA damage response (DDR) pathways. In particular, the application relates to ubiquitin hydrolase protein Ubiquitin Specific Protease 4 (USP4) and its association with DDR pathways. Further, the use of USP4 inhibitors in the treatment of cancer and methods of screening is described, in particular, use of inhibitors of USP4 in the treatment of tumours defective in double-strand break repair (DSBR) and/or tumours resistant to platinum-based chemotherapy, or to sensitise, i.e. chemosensitise or radiosensitise tumours to other therapeutic agents.

Methods of screening and treatment with USP4 inhibitors

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 invention relates to compounds in the treatment or prevention of disorders associated with Lamin A and/or Lamin C depletion or LMNA mutations, such as laminopathy, premature ageing disorders, normal ageing and cancer (such as a cancer characterized by low levels of LMNA expression).

NAT10 modulators for treating or preventing laminopathies, aging and 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&#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

The present invention relates to the cloning and characterization of a prokaryotic DNA repair ligase, which is shown to possess a range of activities that allow the ligation and repair of non-compatible DNA ends and double strand breaks (DSBs). The enzyme has a range of applications in the manipulation and cloning of nucleic acids.

Prokaryotic DNA repair ligases

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.

The interaction of ATM and related protein kinases such as ATR and DNA-PK with p53 is disclosed, in particular the phosphorylation of Ser15 and Thr18 by these proteins. The activity of the proteins is shown to increase in the presence of DNA. Assays for modulators of phosphorylation by the interaction between the proteins and p53 or other proteins having similar phosphorylation sites are provided. Methods of purifying ATM or ATR employing DNA or NTA are also disclosed.

Interactions of ATM, ATR or DAN-PK with p53

The application concerns a compound of formula I:wherein one of P and Q is O, and the other of P and Q is CH, where there is a double bond between whichever of Q and P is CH and the carbon atom bearing the Rgroup;

ATM inhibitors

Growing community of inventors

Cambridge, United Kingdom

Stephen Philip Jackson