St. Jude Children's Research Hospital

Memorial Sloan Kettering Cancer Center

University of Kentucky Research Foundation

Daniel C Scott

Jared T Hammill

Bhuvanesh Singh

Brenda A Schulman

Jaeki Min

R Kiplin Guy

Deepak Bhasin

Jurgen Rohr

Markos Leggas

Oleg Tsodikov

Rodney Kiplin Guy

Brenda Arlene Schulman

Jhong-Min Chen

Julie K Monda

Jerry M Moore

James Caudle

Hoshin Kim

A DCN1/2-mediated cullin neddylation modulator; a method for treating disorders associated with dysfunctional DCN1 and/or UBC12, Alzheimer's disease, other neurodegenerative diseases, bacterial infections, or viral infections; and a method for treating cancers are provided. The DCN1/2-mediated cullin neddylation modulator includes a compound according to Formula I disclosed herein. The methods include administering to a mammal a therapeutically effective amount of a compound according to Formula I. Also provided herein is a pharmaceutical composition including a therapeutically effective amount of a compound according to Formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Pharmaceutically active pyrazolo-pyridone modulators of DCN1/2-mediated cullin neddylation

An apparatus for securely joining ropes for rope suspension or payload tie down. The apparatus includes a two substantially identical channel assemblies configured having a first bend to form a rope groove on one end and a second bend to form a cam channel on the other end, the cam channel having a rivet hole and a pin therethrough to enable a cam to rotate therein, and an attachment mechanism to secure the channel assemblies back-to-back thereto. By opening the cam of either assembly, a rope may be threaded through the rope grove, then again on the opposite assembly. The rope can be pulled from its end away from the assemblies to tighten prior to closing the cam(s) upon the ropes. The rope can further be secured by continuing to pull after the cam has been closed, or by using an optional tightening mechanism and method. A method of tying down cargo or rope suspension using the apparatus of the disclosure for uses such as general-purpose camping, hiking, and other general-purpose tie-down and/or suspension uses of ropes. A method of tightening one or more ropes using the tie-down apparatus disclosed.

Universal tie-down apparatus and method of use

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

Provided herein is a novel binding pocket within NEDD8 co-E3 proteins that binds NEDD8 E2 enzymes. Particularly at its M-Terminus. Methods are provided for screening for compounds that bind to the disclosed E2-binding pocket in NEDD8 co-E3 proteins. Compounds that bind to the E2-binding pocket and optionally inhibit the activity of NEDD8 co-E3 proteins and pharmaceutical compositions comprising the same are further provided. The NEDD8 co-E3 inhibitors find use, as agents preventing the NEDDylation of a target protein, in inhibiting cell growth and methods for treating cancers, inflammatory disorders, and pathogenic infections. The preferred inhibitors are peptides corresponding to a M-terminal fragment of Dnc1, e.g. MTLASKLKRDD, MLKLRQLQKKKQ, and MIKLFSLKQQKK, which are substituted at the M-Terminus with an uncharged group (e.g. acyl).

Methods and compositions for inhibiting neddylation of proteins

Mithramycin derivatives and their pharmaceutically acceptable salts are disclosed. The mithramycin derivatives can be used in the treatment of Ewing sarcoma or other cancer or neuro-disease associated with an aberrant erythroblast transformation-specific transcription factor.

Semi-synthetic mithramycin derivatives with anti-cancer activity

Tanning wand

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Marion, AR, United States of America

Daniel C Scott