Auckland Uniservices Limited

Health Innovation Ventures B.v.

Victoria Link Limited

Guangzhou Institute of Biomedicine and Health

Achilles Medical Limited

Adam Vorn Patterson

Jeffrey Bruce Smaill

Amir Ashoorzadeh

Christopher Paul Guise

William Alexander Denny

William Robert Wilson

Alexandra Marie Mowday

David Francis Ackerley

Janine Naomi Copp

Elsie May Williams

Graham John Atwell

Shangjin Yang

Ho Huat Lee

Guo-Liang Lu

Matthew Roy Bull

Robert Forbes Anderson

Ke Ding

Moana Tercel

Swarnalatha Akuratiya Gamage

Zhengchao Tu

Michael Patrick Hay

Jack Urquhart Flanagan

Xiaomei Ren

Stephen Michael Frazer Jamieson

Christopher John Squire

Ralph James Stevenson

Nuala Ann Helsby

Kendall Marie Carlin

Andrej Maroz

Huai-Ling Annie Hsu

Frederik Bastlaan Pruijn

Sophie Phillipa Syddall

Gareth Adrian Prosser

Nipun Davar

Tillman Pearce

Victoria Jackson

Shevan Silva

Shuang Jiang

Xueqiang Li

Angus Cheverton Grey

Maria Rosaria Abbattista

AKR1C3-activated prodrugs of Formula (I), pharmaceutical compositions comprising prodrugs of Formula (I), and their use in the treatment of hyperproliferative diseases such as cancer and for cell ablation. The compounds of the invention are able to penetrate neoplasm tissue and be selectively reduced to an active (cytotoxic) form by contact with an AKR1C3 enzyme found in the neoplasm. This active form is therefore able to ablate AKR1C3-expressing target cells of the neoplasm and therefore has particular utility in the treatment of cancer and other hyperproliferative disorders. 

Prodrug compounds activated by AKR1C3 and their use for treating hyperproliferative disorders

Fibroblast Growth Factor Receptor kinase inhibitors and prodrugs thereof of Formula (I) and their use for the treatment of hyper-proliferative diseases such as retinopathy, psoriasis, rheumatoid arthritis, osteoarthritis, septic arthritis, tumour metastasis, periodontal disease, corral ulceration, proteinuria, coronary thrombosis from atherosclerotic plaque, aneurismal aorta, dystrophobic epidermolysis bullosa, degenerative cartilage loss following traumatic joint injury, osteopenias mediated by MMP activity, tempero mandibular joint disease, and demyelating disease of the nervous system.

FGFR kinase inhibitors and pharmaceutical uses

Compositions containing and methods of administering TH-4000 are useful in treatment of cancer alone or in combination with other anti-cancer agents.

Kinase inhibitor prodrug for the treatment of cancer

The invention relates generally to bacterial nitroreductase enzymes and methods of use thereof: more particularly, although not exclusively, the enzymes have use in non-invasive imaging techniques, monitoring of therapeutic cell populations and gene-directed enzyme prodrug therapy. The invention also relates to the use of bacterial nitroreductase enzymes in radioimaging and/or ablation of biological agents and to compositions of use in such methods.

Bacterial nitroreductase enzymes and methods relating thereto

The invention relates to compounds of use as targeted cytotoxic agents and methods of use thereof. In particular, the invention relates to prodrugs that are substantially resistant to human AKR1C3 enzyme metabolism, methods of cell ablation using said compounds and methods of treatment of cancer and other hyperproliferative disorders using said compounds.

Prodrugs and methods of use thereof

The invention provides kinase inhibitors of Formula I:  Also provided are reductive prodrugs, comprising a kinase inhibitor as defined above and a reductive trigger linked directly or indirectly to a nitrogen of the kinase inhibitor. Further provided are pharmaceutical compositions, comprising the kinase inhibitors or the prodrugs, and the use of such compositions in therapy, in particular for treating cancer.

Kinase inhibitors, prodrug forms thereof and their use in therapy

The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; Ris a group of the formula &#x2014;(CH)Tr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and &#x2014;(CH)Tr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R, Rand Rmay each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R)(R)(R)N, or two of R, R, and Rmay form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R, Rand Rmay be absent and two of R, Rand Rform an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

Prodrug forms of kinase inhibitors and their use in therapy

Nitroaniline-based unsymmetrical mustards of the general formula (I) are provided, together with methods of preparation and methods for their use as prodrugs for gene-dependent enzyme prodrug therapy (GDEPT) and cell ablation therapy in conjunction with nitroreductase enzymes as hypoxia selective cytotoxins and as anticancer agents.

Nitroaniline-based alkylating agents and their use as prodrugs

The present invention relates generally to nitro-1,2-dihydro-3H-benzo[e]indoles and related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

Nitrobenzindoles and their use in cancer therapy

The present invention relates to a novel nitrophenyl mustard and nitrophenylaziridine alcohols, to their corresponding phosphates, to their use as targeted cytotoxic agents; as bioreductive drugs in hypoxic tumors, and to their use in cell ablation, including gene-directed enzyme-prodrug therapy (GPEPT) and antibody-directed enzymeprodrug therapy (ADEPT), in conjunction with nitroreductase enzymes.

Nitrophenyl mustard and nitrophenylaziridine alcohols and their corresponding phosphates and their use as targeted cytotoxic agents

Growing community of inventors

Auckland, New Zealand

Adam Vorn Patterson