Abstract: Disclosed are bispecific compounds (degraders) that target cereblon (CRBN) for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds as research tools and to reduce adverse side effects associated with a cereblon targeted therapy.

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 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 bispecific compounds (degraders) that target CDK7 for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.

Abstract: Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof. Also disclosed herein are methods of using the compounds of Formula (I) in the treatment of certain diseases (e.g., cancer).

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 bispecific compounds, compositions, and methods for treating diseases or conditions characterized or mediated by aberrant fibroblast growth factor receptor 2 (FGFR2) activity.

Abstract: Disclosed are bifunctional compounds (degraders) that target hepatitis C virus (HCV) NS3/4A for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat HCV infection and HCV-associated diseases or disorders.

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 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: 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: Provided herein are compounds of Formula (I) and pharmaceutical compositions thereof, which may be useful as MALT1 inhibitors. Also provided are for the treatment of proliferative disorders (e.g., cancer (e.g., non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, MALT lymphoma), benign neoplasm, a disease associated with angiogenesis, an autoimmune disease, an inflammatory disease, an autoinflammatory disease) by administering a compound of Formula (I).

Abstract: Provided herein are bifunctional compounds that inhibit MALT1 and/or promote targeted ubiquitination for the degradation of MALT1. In particular, provided are compounds that can bind MALT1, a protein whose activity is responsible for constitutive NF-KB signaling in certain cancers (e.g., activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL)), and can assist in its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon, VHL), which can ubiquitinate MALT1, marking it for proteasome degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating cancer with the bifunctional compounds, methods of promoting the degradation of MALT1, and methods of binding E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.

Abstract: Provided herein are compounds of Formula (I) and pharmaceutical compositions thereof, which may be useful as MALT1 inhibitors. Also provided are for the treatment of proliferative disorders (e.g., cancer (e.g., non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, MALT, lymphoma), benign neoplasm, a disease associated with angiogenesis, an autoimmune disease, an inflammatory disease, an autoinflammatory disease) by administering a compound of Formula (I).

Abstract: The present invention provides a fracturing process, which comprises the following steps of: injecting a fracturing fluid into the formation to cause fractures in the formation and stopping the injection of the fracturing fluid after the fracture as produced reaches a preset requirement; injecting a phase transition material fluid capable of undergoing a phase transition reaction at a preset temperature and a delayed heat generating agent into the formation, wherein the delayed heat generating agent functions to generate heat after the injection of the phase transition material fluid is substantially completed, so as to cause a phase transition of the phase transition material fluid to complete the fracturing. The technical solution provided by the present invention can effectively reduce the friction resistance of the pipe string; moreover, the use of a delayed heat generating agent can effectively control the initiation and progress of the phase transition reaction.

Abstract: Provided herein are bifunctional compounds that inhibit MALT1 and/or promote targeted ubiquitination for the degradation of MALT1. In particular, provided are compounds that can bind MALT1, a protein whose activity is responsible for constitutive NF-KB signaling in certain cancers (e.g., activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL)), and can assist in its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon, VHL), which can ubiquitinate MALT1, marking it for proteasome degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating cancer with the bifunctional compounds, methods of promoting the degradation of MALT1, and methods of binding E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.

Abstract: The present invention discloses a phase change fracturing fluid system for phase change fracturing, including the following components in percentage by weight: 10%-40% of supramolecular construction unit, 0-40% of supramolecular function unit, 0.5%-2% of surfactant, 0-5% of inorganic salt, 0.5%-2% of oxidizing agent, 0-2% of cosolvent and the remaining of solvent. The supramolecular construction unit is melamine, triallyl isocyanurate, or a mixture thereof. The supramolecular function unit is vinyl acetate, acrylonitrile, or a mixture thereof. The solvent is methylbenzene, ethylbenzene, o-xylene, m-xylene or p-xylene. In the fracturing construction process, a conventional fracturing fluid is used for fracturing a formation first; the phase change fracturing fluid is then injected into the formation, or the phase change fracturing fluid and other fluids which cannot be subjected to phase change are injected into the formation together.

Abstract: A phase-change hydraulic fracturing process, including the following steps: (1) injecting clean water or conventional fracturing fluid to a formation, so that the formation fractures; (2) placing non-phase-change liquid and phase-change liquid in different liquid mixing tanks and injecting into a shaft at the same time, an injection volume ratio of the non-phase-change liquid to the phase-change liquid is (0-0.7):(0.3-1); (3) injecting a displacement fluid into the shaft, so that the non-phase-change liquid and the phase-change liquid in the shaft completely enter a reservoir; (4) performing well shut-in and pressure-out for 30-200 min, so that solid-phase matters generated by the phase-change liquid are laid in the fracture; and (5) relieving pressure to finish the construction.