Onyx Therapeutics, Inc.

Cytokinetics, Inc.

Essa Pharma, Inc.

Cleave Biosciences, Inc.

Smithkline Beecham Corporation

The University of British Columbia

Provincial Health Services Authority

California Institute of Technology

University of Kansas

Proteolix, Inc.

Casi Pharmaceuticals, Inc.

Han-Jie Zhou

Guy J Laidig

Kevin D Shenk

Francesco Parlati

Catherine Sylvain

Mark Stephen Smyth

Mark K Bennett

David John Morgans, Jr

Gustave Bergnes

Steven David Knight

Dashyant Dhanak

Peter Virsik

Nicholas D Adams

David Juergen Wustrow

Bing Yao

Congcong M Sun

Hong Jiang

Bradley Paul Morgan

Xiangping Qian

Luke W Ashcraft

Kevin J Duffy

Andrew I McDonald

Cynthia A Parrish

Jianchao Wang

Rosanna Tedesco

Duke Fitch

Jennifer Kuo Chen Huang

Raymond John Andersen

Marianne Dorothy Sadar

Kenneth Allen Newlander

Kunzhong Jian

Daniel Andrew Golec

David Wustrow

Jeffrey Aube

Frank John Schoenen

Samuel Gerritz

Kevin Frankowski

Raymond J Deshaies

Kelin Li

Tsui-Fen Chou

Described herein are crystalline forms of 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, and pharmaceutically acceptable salts and solvates thereof. Also described herein are pharmaceutical formulations of 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide, and pharmaceutically acceptable salts and solvates thereof.

Crystalline forms and formulations of a VCP/p97 inhibitor

The present disclosure generally relates to pharmaceutical compositions and combinations comprising an androgen receptor N-terminal domain inhibitor or an inhibitor and a second therapeutically active agent, such as an CDK4/6 inhibitor, a Pin1 inhibitor (inhibitor of peptidyl-prolyl cis/trans isomerases), or an antiandrogen. In particular, the present disclosure relates to pharmaceutical compositions and combinations useful for treatment of various cancers, for example breast cancer and prostate cancer. Further, the present disclosure relates administering an androgen receptor N-terminal domain inhibitor in combination with radiation therapy for treatment of various cancers.

Pharmaceutical compositions and combinations comprising inhibitors of the androgen receptor and uses thereof

The present invention relates to a crystalline form of Compound I, a salt, a solvate, or a solvate salt thereof or an amorphous form of Compound I, a salt, a solvate, or a solvate salt thereof. The present invention also provides compositions comprising the crystalline form and/or the amorphous form, therapeutic uses of the crystalline forms and/or the amorphous forms, and the compositions thereof.

Solid forms of an N-terminal domain androgen receptor inhibitor and uses thereof

Compounds having a structure of formula (I), (I-A), (Ia)-(Ie), (A)-(E), and (II) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof are provided. Uses of such compounds for modulating androgen receptor activity, imaging diagnostics in cancer and therapeutics, and methods for treatment of disorders including prostate cancer are also provided.

Androgen receptor modulators and methods for their use

Solid forms of an n-terminal domain androgen receptor inhibitor and uses thereof

The present invention relates to compounds of formula (I)-(VI) and/or (A)-(H-I), or any subgenera thereof, or a pharmaceutically acceptable salt, tautomer or stereoisomer. The compounds of the present disclosure are useful in modulating androgen receptor activity and for treating cancer including prostate cancer.

The present invention is directed to certain fused pyrimidines having a homo or hetero cyclopentyl, cyclohexyl or cycloheptyl ring as the pyrimidine fusion partner; having an amino benzyl or substituted amino benzyl group at the 4 position of the pyrimidine ring; and a 5:6 heterobicyclo ring with at least one N, O or S at the 2 position of the pyrimidine ring. These compounds are useful for treatment of cancer by inhibition of the p97 complex.

Fused pyrimidines as inhibitors of p97 complex

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles.

Compounds for enzyme inhibition

Fused pyrimidine compounds having a saturated, unsaturated or aromatic A ring fused to a pyrimidine ring and having a complex substituents at the 2 position and a substituted amine at the 4 position of the pyrimidine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the pyrimidine ring and A ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.

Fused pyrimidines as inhibitors of P97 complex

Monocyclic pyrimidine and pyridine compounds having a benzyl amine substituent at the 4 position and a 5:6 bicyclic heteroaryl substituent at the 2 position of the pyrimidine or pyridine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.

Monocyclic pyrimidine/pyridine compounds as inhibitors of P97 complex

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention.

Disclosed are fused pyrimidine compounds having scaffolds composed of left and right rings, the left ring being a saturated carbocyclic or heterocyclic ring and the right ring being a pyrimidine ring. The left saturated ring is fused to the pyrimidine ring at the 5 and 6 carbons of the pyrimidine. The saturated ring may be 5 or 6 members in size and may be all carbon or may contain a single oxygen, sulfur or nitrogen atom as one of the non-fused members of the ring. The pyrimidine ring is substituted at the two position by a 5:6 bicyclic aromatic heterocycle such as indole, benzimidazole or benzopyrazole and at the four position by an aryl methyl amino group. The 5:6 bicyclic aromatic heterocycle is substituted at its 2 position by hydrogen or an aliphatic or functional aliphatic group and at the 4 position by a functional group as described herein. The aryl methyl amino group may be aminobenzyl or aminomethyl-substituted phenyl. These fused pyrimidine compounds are inhibitors of the AAA proteosome complex containing the enzyme complex p97 and are effective medicinal agents for the treatment of diseases associated with p97 bioactivity such as cancer.

Growing community of inventors

Foster City, CA, United States of America

Han-Jie Zhou