Abstract: Disclosed herein are heterocyclic compounds, for example, according to the following formula and analogs thereof: that inhibit the activity of FLT3. Also described are specific covalent inhibitors of FLT3. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the FLT3 inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of proliferative diseases or conditions, including hematological malignancies and other diseases or conditions dependent on FLT3 activity.

Abstract: Disclosed herein are heterocyclic compounds that inhibit the activity of FLT3. Also described are specific covalent inhibitors of FLT3. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the FLT3 inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of proliferative diseases or conditions, including hematological malignancies and other diseases or conditions dependent on FLT3 activity.

Abstract: An antibody-drug conjugate (ADC) has a structure represented by Formula (I): a pharmaceutically acceptable salt thereof wherein Ab is an antibody without glycans (i.e., the protein portion an antibody); G1 and G2 are glycan moieties, which may be the same or different; Cn1 and Cn2 are conjugation moieties, which may be the same or different; L1 and L2 are linker moieties, which may be the same or different; D1 and D2; are drug units which may be the same or different; and x and y are independently an integer from 0 to 8, provided that x+y?0.

Abstract: Described herein is N-[4-[4-(4-morpholinyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-4-[[3(R)-[(1-oxo-2-propen-1-yl)amino]-1-piperidinyl]methyl]-2-pyridinecarboxamide, including crystalline forms, solvates, and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions that include the compound, as well as methods of using the compound, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract: An antibody-drug conjugate (ADC) has a structure represented by Formula (I): [D2-L2-Cn2yG2-Ab-Sg1G1-L1-D1]x?? Formula (I) or a pharmaceutically acceptable salt thereof, wherein Ab is an antibody without glycans (i.e., the protein portion of an antibody); G1 and G2 are glycan moieties, which may be the same or different; Cn1 and Cn2 are conjugation moieties, which may be the same or different; L1 and L2 are linker moieties, which may be the same or different; D1 and D2 are drug units which may be the same or different; and x and y are independently an integer from 0 to 8, provided that x+y?0.

Abstract: A compound for treating a protein kinase-related disease or disorder having a structure of formula (I) wherein L is NR8 or O; R1, R2, R3, R4, R5, R6 and R7 are defined herein. Compounds of formula (I) are useful for inhibition of protein kinases. Methods of using compounds of formula (I), stereoisomers, tautomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Abstract: The present disclosure relates to anti-SSEA4 antibodies and bindings fragments thereof comprising specific complementarity determining regions capable of high affinity binding to SSEA4 molecules and SSEA4-associated expressing tumor cells, such as breast cancer, pancreatic cancer, and renal cancer cells. The anti-SSEA4 antibodies and binding fragments induce ADCC or CDC effects in the targeted tumor cells and inhibit and/or reduce the cancer/tumor proliferation. The present disclosure also provides anti-SSEA4 antibodies and binding fragments thereof as a pharmaceutical composition for treating cancer. In addition, the anti-SSEA4 antibodies and binding fragments are useful in the diagnosis of cancers.

Abstract: The present disclosure relates to anti-SSEA4 antibodies and bindings fragments thereof comprising specific complementarity determining regions capable of high affinity binding to SSEA4 molecules and SSEA4-associated expressing tumor cells, such as breast cancer, pancreatic cancer, and renal cancer cells. The anti-SSEA4 antibodies and binding fragments induce ADCC or CDC effects in the targeted tumor cells and inhibit and/or reduce the cancer/tumor proliferation. The present disclosure also provides anti-SSEA4 antibodies and binding fragments thereof as a pharmaceutical composition for treating cancer. In addition, the anti-SSEA4 antibodies and binding fragments are useful in the diagnosis of cancers.

Abstract: An antibody-drug conjugate (ADC) has a structure represented by Formula (I): a pharmaceutically acceptable salt thereof wherein Ab is an antibody without glycans (i.e., the protein portion an antibody); G1 and G2 are glycan moieties, which may be the same or different; Cn1 and Cn2 are conjugation moieties, which may be the same or different; L1 and L2 are linker moieties, which may be the same or different; D1 and D2; are drug units which may be the same or different; and x and y are independently an integer from 0 to 8, provided that x+y?0.

Abstract: A mutant of EndoS2 includes one or more mutations in the sequence of a wild-type EndoS2 (SEQ ID NO:1), wherein the one or more mutations are in a peptide region located within residues 133-143, residues 177-182, residues 184-189, residues 221-231, and/or residues 227-237, wherein the mutant of EndoS2 has a low hydrolyzing activity and a high tranglycosylation activity, as compared to those of the wild-type EndoS2. A method for preparing an engineered glycoprotein using the mutant of EndoS2 includes coupling an activated oligosaccharide to a glycoprotein acceptor. The activated oligosaccharide is a glycan oxazoline.

Abstract: A mutant of Endos2 includes one or more mutations in the sequence of a wild-type EndoS2 (SEQ ID NO:1), wherein the one or more mutations are in a peptide region located within residues 133-143, residues 177-182, residues 184-189, residues 221-231, and/or residues 227-237, wherein the mutant of EndoS2 has a low hydrolyzing activity and a high tranglycosylation activity, as compared to those of the wild-type EndoS2. A method for preparing an engineered glycoprotein using the mutant of EndoS2 includes coupling an activated oligosaccharide to a glycoprotein acceptor. The activated oligosaccharide is a glycan oxazoline.

Abstract: The present disclosure relates to anti-SSEA4 antibodies and bindings fragments thereof comprising specific complementarity determining regions capable of high affinity binding to SSEA4 molecules and SSEA4-associated expressing tumor cells, such as breast cancer, pancreatic cancer, and renal cancer cells. The anti-SSEA4 antibodies and binding fragments induce ADCC or CDC effects in the targeted tumor cells and inhibit and/or reduce the cancer/tumor proliferation. The present disclosure also provides anti-SSEA4 antibodies and binding fragments thereof as a pharmaceutical composition for treating cancer. In addition, the anti-SSEA4 antibodies and binding fragments are useful in the diagnosis of cancers.

Abstract: A compound for treating a protein kinase-related disease or disorder having a structure of formula (I) wherein L is NR8 or O; R1, R2, R3, R4, R5, R6 and R7 are defined herein. Compounds of formula (I) are useful for inhibition of protein kinases.

Abstract: A mutant of EndoS2 includes one or more mutations in the sequence of a wild-type EndoS2 (SEQ ID NO: 1), wherein the one or more mutations are in a peptide region located within residues 133-143, residues 177-182, residues 184-189, residues 221-231, and/or residues 227-237, wherein the mutant of EndoS2 has a low hydrolyzing activity and a high tranglycosylation activity, as compared to those of the wild-type EndoS2. A method for preparing an engineered glycoprotein using the mutant of EndoS2 includes coupling an activated oligosaccharide to a glycoprotein acceptor. The activated oligosaccharide is a glycan oxazoline.

Abstract: An antibody-drug conjugate (ADC) has a structure represented by Formula (I): [D2-L2-Cn2?yG2-Ab-Sg1?G1-L1-D1]x?? Formula (I) or a pharmaceutically acceptable salt thereof, wherein Ab is an antibody without glycans (i.e., the protein portion of an antibody); G1 and G2 are glycan moieties, which may be the same or different; Cn1 and Cn2 are conjugation moieties, which may be the same or different; L1 and L2 are linker moieties, which may be the same or different; D1 and D2 are drug units which may be the same or different; and x and y are independently an integer from 0 to 8, provided that x+y?0.

Abstract: A mutant of EndoS2 includes one or more mutations in the sequence of a wild-type EndoS2 (SEQ ID NO: 1), wherein the one or more mutations are in a peptide region located within residues 133-143, residues 177-182, residues 184-189, residues 221-231, and/or residues 227-237, wherein the mutant of EndoS2 has a low hydrolyzing activity and a high tranglycosylation activity, as compared to those of the wild-type EndoS2. A method for preparing an engineered glycoprotein using the mutant of EndoS2 includes coupling an activated oligosaccharide to a glycoprotein acceptor. The activated oligosaccharide is a glycan oxazoline.

Abstract: A compound or its pharmaceutically acceptable salt, optionally including both individual enantiomeric forms, a racemate, diastereomers and mixtures thereof, composition and method are disclosed that can provide analgesia and reduce inflammation. A contemplated compound has a structure that corresponds to Formula A, wherein the R group substituents, d, e, f, k, n, m, D, E, F, K, G, P, Q, W, and Z are defined within.

Abstract: A compound for treating a protein kinase-related disease or disorder having a structure of formula (I) wherein G is a heteroaryl, heterocyclic or alkyne; X is N or CH; L1 is —N(R7)—, —O—, —C(S)—, —C(O)—, or —S—; L2 is —N(R8)— or —O—; R1 and R2 are independently hydrogen, halogen, hydroxyl, amino, cyano, nitro, carboxy, C1-C4 alkoxy, C1-C4 alkoxy C1-C4 alkoxy, N,N—(C1-C4 dialkyl)amino C1-C4 alkoxy, N—(C1-C4 alkyl)amino C1-C4 alkoxy, C1-C4 alkanoyl, C1-C4 alkanoyloxy, N—(C1-C4 alkyl)amino, N,N—(C1-C4 dialkyl)amino, C1-C4 alkanoyl amino, or heterocyclyl, wherein C1-C4 alkyl is optionally substituted with one or more substituents selected from fluorine and chlorine; R3, R4 and R5 are independently hydrogen, fluorine or chlorine; R6 is C1-C4 alkyl or aryl, which is optionally substituted with one or more substituents selected from halogen, hydroxyl, amino, cyano, nitro; or R6 and R8 form a 5-6 membered cyclyl or heterocyclyl.

Abstract: A compound for treating a protein kinase-related disease or disorder having a structure of formula (I) wherein G is a heteroaryl, heterocyclic or alkyne; X is N or CH; L1 is —N(R7)—, —O—, —C(S)—, —C(O)—, or —S—; L2 is —N(R8)— or —O—; R1 and R2 are independently hydrogen, halogen, hydroxyl, amino, cyano, nitro, carboxy, C1-C4 alkoxy, C1-C4 alkoxy C1-C4 alkoxy, N,N—(C1-C4 dialkyl)amino C1-C4 alkoxy, N—(C1-C4 alkyl)amino C1-C4 alkoxy, C1-C4 alkanoyl, C1-C4 alkanoyloxy, N—(C1-C4 alkyl)amino, N,N—(C1-C4 dialkyl)amino, C1-C4 alkanoyl amino, or heterocyclyl, wherein C1-C4 alkyl is optionally substituted with one or more substituents selected from fluorine and chlorine; R3, R4 and R5 are independently hydrogen, fluorine or chlorine; R6 is C1-C4 alkyl or aryl, which is optionally substituted with one or more substituents selected from halogen, hydroxyl, amino, cyano, nitro; or R6 and R8 form a 5-6 membered cyclyl or heterocyclyl.

Abstract: A compound or its pharmaceutically acceptable salt, optionally including both individual enantiomeric forms, a racemate, diastereomers and mixtures thereof, composition and method are disclosed that can provide analgesia and reduce inflammation. A contemplated compound has a structure that corresponds to Formula A, wherein the R group substituents, d, e, f, k, n, m, D, E, F, K, G, P, Q, W, and Z are defined within.