Abstract: Disclosed are compounds with immunomodulatory activity, methods of making the compounds, pharmaceutical compositions containing the compounds, and methods of using the compounds to treat diseases or disorders characterized or mediated by dysfunctional protein activity.

Abstract: A cartridge for a laundry appliance includes an outer housing having an interior chamber therein. The outer housing includes a primary axis and a secondary axis that is perpendicular to the primary axis. A pump is contained within the outer housing that selectively delivers a laundry chemistry from the interior chamber to a dispensing outlet of the outer housing. The dispensing outlet is defined within a contoured edge of the outer housing and orients the dispensing outlet at an oblique angle with respect to the primary and secondary axes. A rotational drive is operated by an external actuator. The rotational drive is positioned within the outer housing and in operable communication with the pump. The rotational drive aligns with a drive aperture defined within a wall of the outer housing for receiving the external actuator.

Abstract: A truck and automotive cab storage box is placed in the back seat of the cab of a work truck or other vehicle. The truck and automotive cab storage box has a tray which is connected to an angled cover and a divider separates the tray into two sections. The truck and automotive cab storage box stores items and forces users to stop the vehicle and open the rear doors to access items in or underneath the tray. The angled cover makes it difficult or impractical to store items on top of the truck and automotive cab storage box. The truck and automotive cab storage box makes it difficult or impractical to store items around it.

Abstract: A system may detect a vibration being applied to a tuned vibration absorber. The tuned vibration absorber may include a beam, a mass, springs, a sensor, and an actuator. The mass may be disposed on the beam at a current position. The actuator may be configured to adjust a position of the mass on the beam. The system may identify a target position of the mass on the beam based on the detected vibration. The system may generate a drive signal, based on the target position, to control the actuator to adjust the position of the mass on the beam. The system may control the actuator to adjust the position of the mass from the current position on the beam to the target position on the beam to attenuate the vibration.

Abstract: Disclosed are bifunctional compounds comprising a GDC-0068 analog that binds AKT isoforms AKT1, 2 and 3, pharmaceutical compositions, and methods for treating diseases or conditions mediated by dysfunctional AKT activity.

Abstract: Disclosed are compounds and pharmaceutically acceptable salts and stereoisomers thereof that may cause degradation of various proteins e.g., IKZF2 (Helios). Also disclosed are pharmaceutical compositions containing same, and methods of making and using the compounds to treat diseases and disorders characterized or mediated by aberrant protein activity.

Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by Kelch-like ECH-associated protein 1 (KEAP1). In some aspects, the present invention is directed to methods of treating diseases or disorders involving dysfunctional (e.g., dysregulated) KEAP1 activity, that entails administration of a therapeutically effective amount of a bifunctional compound of formula I or a pharmaceutically acceptable salt or stereoisomer thereof, to a subject in need thereof.

Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by dysfunctional cyclin-dependent kinase 2 (CDK2) and CDK5 activity.

Abstract: Described herein are compositions and methods for modulating protein abundance in a target-specific manner via degron tags.

Abstract: Disclosed are degraders, pharmaceutical compositions containing them, and methods of making and using the degraders to treat diseases and disorders characterized by aberrant protein activity that can be targeted by cereblon.

Abstract: Disclosed are compounds with immunomodulatory activity, methods of making the compounds, pharmaceutical compositions containing the compounds, and methods of using the compounds to treat diseases or disorders characterized or mediated by dysfunctional protein activity.

Abstract: Disclosed are immunomodulatory compounds, pharmaceutical compositions containing them, and methods of making and using the compounds to treat diseases and disorders characterized by aberrant protein activity that can be targeted by cereblon.

Abstract: Disclosed are degraders, pharmaceutical compositions containing them, and methods of making and using the degraders to treat diseases and disorders characterized by dysregulated or dysfunctional protein activity that can be targeted by cereblon.

Abstract: Disclosed are bifunctional compounds, pharmaceutical compositions containing them, and methods of making and using them to treat diseases and disorders characterized by aberrant protein activity wherein the protein is targeted for degradation by KEAP1 and the Cul3-based E3-ubiquitin ligase complex.

Abstract: The present invention relates to compounds, compositions and methods for treating diseases or conditions mediated by proteins of the SWI/SNF chromatin-remodeling complex, including PB1.

Abstract: Disclosed herein are protein-targeting chimeric molecules (PROTACs) that recruit a specific ubiquitin ligase, such as LRL4DCAF15, to a chosen target protein, causing its degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.

Abstract: DCAF15 is a substrate recognition (adaptor) protein of E3 ubiquitin ligase. Disclosed herein are compounds that recruit ubiquitin ligase CRL4DCAF15, to a target RNA recognition motif (RRM), causing its degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.

Abstract: A method for generating a dimerization and/or degradation moiety for a first protein and a second protein, where the method includes (a) generating, in silico a set of poses by docking a first protein, and a second protein, (b) generating a subset of poses by selecting one or more poses from the set of poses based on the scores of the poses, (c) identifying a candidate pose from the subset of poses based on the spatial relationship between the two proteins, (d) designing a linker between the first ligand and the second ligand that accommodates the candidate pose, and (e) synthesizing or having synthesized the dimerization and/or degradation moiety having the first ligand, the second ligand, and the linker.

Abstract: An adjusting device is proposed for adjusting a first component and a second component of a passenger or freight transport vehicle relative to each other, wherein the two components are arranged adjacent to each other to form a gap. The device includes a base body, an adjusting element mounted in the base body and movable along a first axis and an actuating body mounted in the base body and movable along a second axis which cooperates with the adjusting element such that the movement of the adjusting element along the first axis converted into a movement of the actuating body and/or the adjusting element along the second axis; and a fixing device for fixing the adjusting element and the actuating body in a selectable position. The invention also relates to a passenger or freight transport vehicle with such a device.