St. Jude Children's Research Hospital

Memorial Sloan Kettering Cancer Center

Creighton University

St. Jude Children's Research Hospital, Inc. (tennessee Not for Profit Corporation)

Ting Therapeutics LLC

Jaeki Min

R Kiplin Guy

Jian Zuo

Nagakumar Bharatham

Brandon M Young

Daniel C Scott

Jared T Hammill

Bhuvanesh Singh

Michael Dyer

Richard Kriwacki

Brenda A Schulman

Antonio Ferreira

Lie Min

Donald Bashford

Kristin Finch

Yiqun Zhang

Deepak Bhasin

Taosheng Chen

Zoran Rankovic

Sourav Das

Gisele A Nishiguchi

Kevin Mcgowan

Yunchao Chang

Jeanine Price

Fatemeh Keramatnia

Charles G Mullighan

Grace Roy-Appa

Tal Teitz

Marisa Laura Zallocchi

Fei Zheng

Santanu Hati

Tetsuji Yamashita

Tai Teitz

Robert Hazlitt

Grace Royappa

Marcus Fisher

Asli Goktug

Jie Fang

Zoe Kellard

Marcus Fischer

Anthony Ferreira

In one aspect, the disclosure relates to substituted N-(2-(2,6-dioxopiperidinyl-3-yl)-1,3-dioxoisoindolin-5-yl)arylsulfo namide analogs that useful as modulators of cereblon (CRBN) activity, methods of making same, pharmaceutical compositions comprising same, and methods of treating various clinical conditions and disorders using same, e.g., a disorder of uncontrolled cellular proliferation, such as a cancer, which may be associated with cereblon protein dysfunction and/or a GSPT1 dysfunction. In various further aspects, the disclosed compounds can selectively modulate the degradation of GSPT1 protein, i.e., the disclosed compounds can act as GSPT1 degraders. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Substituted N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)arylsulfonamide analogs as modulators of cereblon protein

In one aspect, the disclosure relates to substituted N-(2-(2,6-dioxopiperidinyl-3-yl)-1,3-dioxoisoindolin-5-yl)arylsulfonamide analogs that useful as modulators of cereblon (CRBN) activity, methods of making same, pharmaceutical compositions comprising same, and methods of treating various clinical conditions and disorders using same, e.g., a disorder of uncontrolled cellular proliferation, such as a cancer, which may be associated with cereblon protein dysfunction and/or a GSPT1 dysfunction. In various further aspects, the disclosed compounds can selectively modulate the degradation of GSPT1 protein, i.e., the disclosed compounds can act as GSPT1 degraders. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

In one aspect, the invention relates to substituted 1-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1-mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Methods and compositions of inhibiting DCN1-UBC12 interaction

Methods and compositions using an inhibitor of EGFR signaling for prevention or an inhibitor of EGFR signaling and a nucleic acid molecule encoding an atonal-associated factor for treatment of hearing loss are described.

Compositions and methods for prevention and treatment of hearing loss

Provided are CDK2-PROTAC compounds and pharmaceutical compositions thereof that can be used for specific degradation of the cyclin-dependent kinase 2 (CDK2) protein, for treatment of cancers and other CDK2 related diseases as well as for prevention and treatment of hearing loss.

Compositions, use, and method for CDK2-PROTACs for cancer therapy and hearing loss

In one aspect, pharmaceutical compositions comprising a CDK2 inhibitor and one or more of at least one agent known to treat a hearing impairment and at least one agent known to prevent a hearing impairment, and methods of treating and/or preventing hearing impairments or disorders using the compositions are disclosed. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Methods and compositions for the prevention and treatment of hearing loss

The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Aryl-substituted imidazoles

Growing community of inventors

Memphis, TN, United States of America

Jaeki Min