Abstract: The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof; wherein: n is 1 or 2; X is CH or N; Y is selected from CH and C—F; Z is selected from C—Rz and N; R1 is selected from: -(Alk1)t-Cyc1; wherein t is 0 or 1; Optionally substituted C1-6 acyclic hydrocarbon groups R2 is selected from hydrogen; halogen; and C1-3 hydrocarbon groups optionally substituted with one or more fluorine atoms; R3 is hydrogen or a group L1-R7; R4 is selected from hydrogen; methoxy; and optionally substituted C1-3 alkyl; and R4a is selected from hydrogen and a C1-3 alkyl group; wherein Rz, Alk1, Cyc1, L1 and R7 are defined herein; provided that the compound is other than 6-benzyl-3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and 3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and salts and tautomers thereof.

Abstract: The present disclosure provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: The present disclosure provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: The present disclosure provides carboxamides and sulfonamides having Formula (I); and the pharmaceutically acceptable salts and solvates thereof, wherein A, Y, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

Abstract: The present disclosure provides substituted indole compounds of Formula I: (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R1a, R1e, G1, G2, Q1, Q2, Q3, and (II) are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disease, disorder, or condition such as cancer in a subject.

Abstract: The present disclosure provides novel cancer therapies. The treatment of cancers harboring EP300 mutations with CREBBP inhibition therapy is described.

Abstract: This disclosure generally relates to pyridine-2-one compounds of formula (I) and methods of using them in the treatment of a disorder, such as cancer or a SMARCA2-associated disorder, including as antagonists (e.g., inhibitors) of SMARCA2. The present disclosure provides treatment modalities, e.g., strategies, treatment methods, patient stratification methods, compounds, combinations, and compositions that are useful for the treatment of disorders, e.g., proliferative disorders, such as certain cancers. Some aspects of this disclosure provide treatment modalities, methods, strategies, compounds, compositions, combinations, and dosage forms for the treatment of cell proliferative disorders, e.g., cancers with decreased activity or function, or loss of function, of SMARCA4 with a SMARCA2 antagonist.

Abstract: The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: An assembly for offsite construction of a building, a connector for use in such an assembly, along with a method of manufacture of such a connector, and a method of construction using the assembly. The connector includes first and second buttress elements defining, respectively, a first location portion and a second location portion. The first location portion and the second location portion are configured, respectively, to receive first and second structural elements extending at transverse angles to each other. The first and second buttress elements each has first and second opposite side walls defining an access space between them for a connector to be accessed. The second side wall of the first buttress element and the second side wall of the second buttress element together define a third location portion configured to receive a third structural element extending transversely to the first and second structural elements.

Abstract: An oilfield band cutter is useful for removing a band from a tubing string structure as the tubing string structure is being pulled up from the well. The oilfield band cutter includes a base frame with a central hole, an axis extending vertically and centrally through the frame coaxial with the central hole. A tubing follower member is coupled to the base frame and is positioned against an outer surface of the tubing string structure. A cutter is coupled to the tubing follower member, the cutter including an underside having a cutting edge. The cutting edge is positioned to engage against and cut bands on the tubing string structure.

Abstract: The present disclosure provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: An oilfield band cutter is useful for removing a band from a tubing string structure as the tubing string structure is being pulled up from the well. The oilfield band cutter includes a base frame with a central hole, an axis extending vertically and centrally through the frame coaxial with the central hole. A tubing follower member is coupled to the base frame and is positioned against an outer surface of the tubing string structure. A cutter is coupled to the tubing follower member, the cutter including an underside having a cutting edge. The cutting edge is positioned to engage against and cut bands on the tubing string structure.

Abstract: The present disclosure provides carboxamides and sulfonamides having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, Y, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such a SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

Abstract: The present disclosure relates to amine-substituted aryl or heteroaryl compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating a disorder (e.g., sickle cell anemia) via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2, by administering an amine-substituted aryl or heteroaryl compound disclosed herein or a pharmaceutical composition thereof to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.

Abstract: The present disclosure provides substituted isoxazole carboxamide compounds having Formula (1) and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, A, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2 Compounds of the present disclosure are especially useful for treating cancer.

Abstract: The present disclosure provides substituted pyrrolidine compounds having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein R1, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

Abstract: The present disclosure provides pyrrolidine carboxamide compounds having Formula I and the pharmaceutically acceptable salts and solvates thereof, wherein A, B, X, Y, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

Abstract: The present disclosure provides carboxamides and sulfonamides having Formula (I): and the pharmacentically acceptable salts and solvates thereof, wherein A, Y, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

Abstract: The present disclosure provides substituted isoxazole carboxamide compounds having Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, A, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.