Abstract: Provided herein are RAS protein degraders, e.g., a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a RAS-mediated disorder, disease, or condition.

Abstract: Provided herein are phosphodiesterase 4 (PDE4) inhibitors, e.g., a compound of Formula (I) or (II), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a disease, disorder, or condition associated with PDE4 malfunction.

Abstract: Provided herein are non-hygroscopic crystalline salts of (1r,4r)-N1-(5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)cyclohexane-1,4-diamine and pharmaceutical compositions thereof. Also provided are methods of their use for treating, preventing, or ameliorating one or more symptoms of a proliferative disease.

Abstract: An electrical connector housing is provided. A slot is provided in the housing between a plurality of contact blades and the front surface of the electrical connector housing. The slot extends perpendicularly from the top surface of the electrical connector housing to communicate with a plurality of passages in the housing for receiving insulated wires. A cutting blade is received and secured in the slot for cutting portions of the insulated wires that exceed the slot or the cutting blade in the lengthwise direction of the electrical connector housing. The housing is able to prevent electrical shorts, sparks and other electrical risks arising from exposed or open wire ends on the connector.

Abstract: An electrical connector, having an elongated plastic housing which is open at its rearward end and has an essentially continuous forward end wall with a flat upper portion, a lower portion of the forward end wall being integrally thickened to project forward beyond its upper portion.

Abstract: An electrical connector, having an elongated plastic housing which is open at its rearward end and has an essentially continuous forward end wall with a flat upper portion, a lower portion of the forward end wall being integrally thickened to project forward beyond its upper portion.

Abstract: Provided herein are phosphodiesterase 4 (PDE4) degraders, e.g., a compound of Formula (I) or (IA), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a PDE4-mediated disease, disorder, or condition.

Abstract: An electrical connector, having an elongated plastic housing which is open at its rearward end and has an essentially continuous forward end wall with a flat upper portion, a lower portion of the forward end wall being integrally thickened to project forward beyond its upper portion.

Abstract: An electrical connector, having an elongated plastic housing which is open at its rearward end and has an essentially continuous forward end wall with a flat upper portion, a lower portion of the forward end wall being integrally thickened to project forward beyond its upper portion.

Abstract: Provided herein are substituted biaryl sulfonamide compounds, pharmaceutical compositions comprising the compounds, methods of their preparation, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or amelioration of various disorders, including cancer and proliferative disorders. In one embodiment, the compounds provided herein modulate initiation of protein translation. In one embodiment, the compounds provided herein are used in combination with surgery, radiation therapy, immuno therapy and/or one or more additional anticancer drugs for the treatment, prevention, and/or amelioration of cancer and proliferative disorders.

Abstract: Provided herein are a biarylsulfonamide, e.g., a compound of Formula (IA), and a pharmaceutical composition thereof. Also provided herein is a method of treating a fibrotic lung disease with a biarylsulfonamide, alone or in combination with an antifibrotic agent. Additionally, provided herein is a method of slowing the rate of decline in pulmonary function in a subject having a fibrotic lung disease with a biarylsulfonamide, alone or in combination with an antifibrotic agent.

Abstract: Provided herein are phosphodiesterase 4 (PDE4) inhibitors, e.g., a compound of Formula (I) or (II), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a disease, disorder, or condition associated with PDE4 malfunction.

Abstract: Provided herein is a method of treating, preventing, or ameliorating one or more symptoms of relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndrome using a pyrazolylpyrimidine, e.g., a compound of Formula (I).

Abstract: Provided herein are RAS protein degraders, e.g., a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a RAS-mediated disorder, disease, or condition.

Abstract: Provided herein are non-hygroscopic crystalline salts of (1r,4r)-N1-(5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)cyclohexane-1,4-diamine and pharmaceutical compositions thereof. Also provided are methods of their use for treating, preventing, or ameliorating one or more symptoms of a proliferative disease.

Abstract: The present disclosure provides compounds, for example, a compound of Formula (I), that modulate a protein function and/or restore protein homeostasis. The disclosure provides a method of modulating a protein-mediated disease, disorder, condition, or response. Compositions, including in combination with other therapeutic agents, are provided.

Abstract: Compounds with amino amide linkers and pharmaceutical compositions and medicaments comprising such compounds are disclosed. In addition, methods of making such compounds and their uses for treating or ameliorating diseases, disorders, or conditions associated with protein malfunction, such as cancer, are provided.

Abstract: Substituted isoindolinones of Formula (I), methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat or ameliorate diseases, disorders, or conditions associated with protein malfunction, such as cancer, are provided.

Abstract: The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CK1?, GSPT1, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.

Abstract: The present application provides compounds that modulate CDK protein function. Methods of making the compounds, compositions containing the compounds, and uses of the compounds for treating or ameliorating of diseases, disorders, or conditions associated with CDK proteins, are also disclosed.