Provided herein are methods and compositions for treating cancers, inflammatory diseases, rasopathies, and fibrotic disease involving aberrant Ras superfamily signaling through the binding of compounds to the GTP binding domain of Ras superfamily proteins including, in certain cases, K-Ras and mutants thereof, and a method for assaying such compositions.

PDL1-pHLIP, a preparation method of the PDL1-pHLIP, and an application of the PDL1-pHLIP in treatment of autoimmune diseases are provided. A fusion peptide is prepared by binding a pH low insertion peptide and an extracellular domain of PDL1. The pH low insertion peptide may be inserted onto a cell membrane of a focus tissue in an acid environment; the PDL1 bound to the pH low insertion peptide is subjected to targeting localization at the focus by utilizing the above properties of the pH low insertion peptide; a PD-1/PD-L1 negative signal of the focus tissue is enhanced by utilizing the pH low insertion peptide; and immune response of effector T cells is suppressed at the source, thereby achieving an effect of preventing and treating the autoimmune diseases.

PDL1-pHLIP, a preparation method of the PDL1-pHLIP, and an application of the PDL1-pHLIP in treatment of autoimmune diseases are provided. A fusion peptide is prepared by binding a pH low insertion peptide and an extracellular domain of PDL1. The pH low insertion peptide may be inserted onto a cell membrane of a focus tissue in an acid environment; the PDL1 bound to the pH low insertion peptide is subjected to targeting localization at the focus by utilizing the above properties of the pH low insertion peptide; a PD-1/PD-L1 negative signal of the focus tissue is enhanced by utilizing the pH low insertion peptide; and immune response of effector T cells is suppressed at the source, thereby achieving an effect of preventing and treating the autoimmune diseases.

Compositions and methods are provided for inhibiting T cell mediated destruction of virally transduced, trangene containing cells.

Disclosed is a compound capable of inhibiting interleukin 17A (IL-17A), which is represented by formula (I). An application of the compound or a stereoisomer thereof in the preparation of drugs for inhibiting IL-17A is also provided.

##STR00001##

A compound having one of the following structures of Formula (IV) or (V):

##STR00001##

or a stereoisomer, salt, or tautomer thereof, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 R.sub.6, R.sub.7, R.sub.8, R.sub.10, R.sub.11a R.sub.11b, R.sub.12a R.sub.12b, X, Y, and Z are as defined herein. Pharmaceutical composition comprising the compounds, and their use in methods of treating diseases are also described.

Provided are anti-PD-1 antibodies or fragments thereof. In various example, the antibodies or fragments thereof includes a heavy chain variable region comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and a light chain variable region comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3. Methods of using the antibodies or fragments thereof for treating and diagnosing diseases such as cancer, infection or immune disorders are also provided.

Provided are anti-PD-1 antibodies or fragments thereof. In various example, the antibodies or fragments thereof includes a heavy chain variable region comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and a light chain variable region comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3. Methods of using the antibodies or fragments thereof for treating and diagnosing diseases such as cancer, infection or immune disorders are also provided.

The invention provides an antibody comprising human IgG1 or IgG3 heavy chain constant domains that are glycosylated with a sugar chain at Asn297, said antibody being characterized in that the amount of fucose within said sugar chain is at least 99%, and in addition the amount of NGNA is 1% or less and/or the amount of N-terminal alpha 1,3 galactose is 1% or less, and uses thereof.

A compound of formula (I):

##STR00001##

wherein: R.sup.1 is selected from (i) H, (ii) C.sub.3-6cycloalkyl, (iii) C.sub.3-7heterocyclyl optionally substituted with a group selected from: methyl and ester, and (iv) linear or branched C.sub.1-4alkyl optionally substituted with a group selected from: alkoxy, amino, amido, acylamido, acyloxy, alkyl carboxyl ester, alkyl carbamoyl, alkyl carbamoyl ester, phenyl, phosphonate ester, C.sub.3-7heterocyclyl optionally substituted with a group selected from methyl and oxo, and a naturally occurring amino acid, optionally N-substituted with a group selected from methyl, acetyl and boc; A.sup.1 is CR.sup.A or N; A.sup.2 is CR.sup.B or N; A.sup.3 is CR.sup.C or N; A.sup.4 is CR.sup.D or N; where no more than two of A.sup.1, A.sup.2, A.sup.3, and A.sup.4 may be N; one or two of R.sup.A, R.sup.B, R.sup.C, and R.sup.D, (if present) are selected from H, F, Cl, Br, Me, CF.sub.3, cyclopropyl, cyano, OMe, OEt, CH.sub.2OH, CH.sub.2OMe and CH.sub.2NMe.sub.2; the remainder of R.sup.A, R.sup.B, R.sup.C, and R.sup.D, (if present) are H; Y is O, NH or CH.sub.2; R.sup.Y is selected from: (RYA) and (RYB).