Auckland Uniservices Limited

Genentech, Inc.

Guo-Liang Lu

William Alexander Denny

Ho Huat Lee

Gordon William Rewcastle

Muriel Bonnet

John A Flygare

Brian Salvatore Safina

Thomas Pillow

BinQing Wei

William Robert Wilson

Vishal Verma

Jeffrey Bruce Smaill

Binqing Wei

Adam Vorn Patterson

Moana Tercel

Amir Ashoorzadeh

Anna Giddens

Christian Miller

Stephen Michael Frazer Jamieson

Robert Forbes Anderson

Swarnalatha Akuratiya Gamage

Michael Patrick Hay

Jack Urquhart Flanagan

Alexandra Marie Mowday

Christina Maree Buchanan

Andrew James Marshall

Peter Robin Shepherd

Huai-Ling Annie Hsu

Andrej Maroz

Kendall Marie Carlin

Thomas H Pillow

Disclosed are tricyclic heterocyclic compounds having kinase inhibitory activity, pharmaceutical compositions and kits comprising the compounds, and use of the compounds in the treatment of or in medicaments for the treatment of various diseases and conditions. In particular, disclosed are tricyclic heterocyclic compounds of the formula (I) having CSF-1R (c-FMS kinase) inhibitory activity and their use in the treatment of various diseases and conditions, such as those mediated by CSF-1R, including proliferative or neoplastic diseases and conditions, including cancers, and bone, inflammatory, and autoimmune diseases and conditions.

Tricyclic heterocyclic derivatives and uses thereof

The invention provides antibody-drug conjugates comprising an antibody conjugated to a 1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimer drug moiety via a linker, and methods of using the antibody-drug conjugates.

1-(Chloromethyl)-2,3-dihydro-1H-benzo[e]indole dimer antibody-drug conjugate compounds, and methods of use and treatment

1-(chloromethyl)-2,3-dihydro-1H-benzo[E]indole dimer antibody-drug conjugate compounds, and methods of use and treatment

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

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Auckland, New Zealand

Guo-Liang Lu