Abstract: A strong FXR small-molecule agonist, and a preparation method therefor and use thereof, the structure of the agonist being represented by formula (I), are provided. In the formula, each substituent is as defined in the description and the claims. The compound provided has the advantages of high FXR agonist activity, simple synthesis, easily available raw materials and the like, and can be used for preparing medicines for treating FXR related diseases.

Abstract: A salt of nucleoside analog, and crystal form, pharmaceutical composition and use thereof. The salt of nucleoside analog has a structure shown in formula I, wherein X is hydrogen or deuterium; Y is an acid, n is 0.5 to 2, or n is 1. When X is hydrogen or deuterium, Y is hydrogen bromide, and n is 1, the salt of the nucleoside analog exists in the form of a crystal with crystal form I or crystal form A or exists in an amorphous form.

Abstract: An FXR small molecule agonist and a preparation method therefor and a use thereof, having a structure as shown in formula (I). The compound represented by formula (I) has FXR agonistic activity and is capable of preparing drugs for treatment of FXR-related diseases.

Abstract: Disclosed herein are a liver specific delivery (LSD)-based antiviral prodrug nucleoside cyclophosphate compound and uses thereof. Specifically, this application provides a compound of formula (I), or an isomer, a pharmaceutically acceptable salt, a hydrate, a solvate or a pharmaceutical composition thereof. This application also provides an application of the compound alone or in combination with other antiviral drugs in the treatment for viruses, particularly hepatitis C virus (HCV).

Abstract: Disclosed is a liver specific delivery (LSD)-based entecavir antiviral prodrug, i.e., a nucleoside cyclic phosphate compound, and the application thereof. Specifically, disclosed are a compound as represented by formula (I) and isomers, pharmaceutically acceptable salts, hydrates, and solvates of the compound, and a corresponding pharmaceutical composition. Also disclosed is the application of the compound of the present invention, used separately or used in combination with other antiviral drugs, against viruses, especially the application against hepatitis B virus (HBV).

Abstract: Provided are a liver specific delivery (LSD)-based anticancer prodrug nucleoside cyclic phosphate compound and an application thereof, and in particular, a compound represented by formula (I) as well as isomers, pharmaceutically acceptable salts, hydrates, and solvates thereof, and corresponding pharmaceutical compositions. Also provided is an application of the compound alone or in combination with other anticancer drugs in anticancer area, particularly the treatment of hepatocellular carcinoma (HHC).

Abstract: Disclosed are an anticancer prodrug nucleoside cyclic phosphate compound based on liver-specific delivery (LSD) technology and the use thereof, in particular, provided are a compound of formula (I) and an isomer, a pharmaceutically acceptable salt, a hydrate, a solvate and a corresponding pharmaceutical composition thereof, and the use of the compound alone or in combination with other anticancer drugs against cancer, especially in treating hepatic carcinoma (HCC).

Abstract: Disclosed is a liver specific delivery (LSD)-based entecavir antiviral prodrug, i.e., a nucleoside cyclic phosphate compound, and the application thereof. Specifically, disclosed are a compound as represented by formula (I) and isomers, pharmaceutically acceptable salts, hydrates, and solvates of the compound, and a corresponding pharmaceutical composition. Also disclosed is the application of the compound of the present invention, used separately or used in combination with other antiviral drugs, against viruses, especially the application against hepatitis B virus (HBV).

Abstract: Provided are a liver specific delivery (LSD)-based anticancer prodrug nucleoside cyclic phosphate compound and an application thereof, and in particular, a compound represented by formula (I) as well as isomers, pharmaceutically acceptable salts, hydrates, and solvates thereof, and corresponding pharmaceutical compositions. Also provided is an application of the compound alone or in combination with other anticancer drugs in anticancer area, particularly the treatment of hepatocellular carcinoma (HHC).

Abstract: Disclosed are an anticancer prodrug nucleoside cyclic phosphate compound based on liver-specific delivery (LSD) technology and the use thereof, in particular, provided are a compound of formula (I) and an isomer, a pharmaceutically acceptable salt, a hydrate, a solvate and a corresponding pharmaceutical composition thereof, and the use of the compound alone or in combination with other anticancer drugs against cancer, especially in treating hepatic carcinoma (HCC).

Abstract: Disclosed are a liver specific delivery (LSD)-based antiviral prodrug nucleoside cyclophosphate compound and uses thereof, and in particular, provided are a compound of formula (I), and an isomer, a pharmaceutically acceptable salt, a hydrate and a solvate thereof, and the corresponding pharmaceutical composition. The present invention also provides uses of the present compounds, alone or in combination with other antiviral drugs, in the treatment of the diseases caused by hepatitis B virus (HBV), hepatitis D virus (HDV) and human immunodeficiency virus (HIV).

Abstract: Disclosed is a compound of formula (I-a) as an inhibitor of hepatitis C virus (HCV), or an optical isomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof, usable to treat HCV infections or hepatitis C diseases and also usable as an inhibitor of HCV non-structural protein 5A (NS5A) In the formula (I-a), A and A? are independently each R1, R4 and R6 are independently selected from the group consisting of fluorine, chlorine, bromine and iodine; R2 and R2? are independently selected from substituted or unsubstituted C1-C6 alkyl; R3 and R3? are independently selected from substituted or unsubstituted C1-C6 alkyl; R5 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine and iodine; n is 2, 3, 4 or 5; m is 0, 1, 2 or 3; and p is 0, 1, 2 or 3.

Abstract: Disclosed herein are a liver specific delivery (LSD)-based antiviral prodrug nucleoside cyclophosphate compound and uses thereof. Specifically, this application provides a compound of formula (I), or an isomer, a pharmaceutically acceptable salt, a hydrate, a solvate or a pharmaceutical composition thereof. This application also provides an application of the compound alone or in combination with other antiviral drugs in the treatment for viruses, particularly hepatitis C virus (HCV).

Abstract: Disclosed is a compound of formula (I) as an inhibitor of hepatitis C virus (HCV), or an optical isomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof, usable to treat HCV infections or hepatitis C diseases, and is also useful as an inhibitor of HCV non-structural protein 5A (NS5A).

Abstract: Disclosed are a liver specific delivery (LSD)-based antiviral prodrug nucleoside cyclophosphate compound and uses thereof, and in particular, provided are a compound of formula (I), and an isomer, a pharmaceutically acceptable salt, a hydrate and a solvate thereof, and the corresponding pharmaceutical composition. The present invention also provides uses of the present compounds, alone or in combination with other antiviral drugs, in the treatment of the diseases caused by hepatitis B virus (HBV), hepatitis D virus (HDV) and human immunodeficiency virus (HIV).

Abstract: The inventors disclose a 1.95 ? crystal structure of the MR ligand binding domain containing a single C808S mutation bound to a corticosterone and the fourth LXXLL motif of steroid receptor coactivator-1 (SRC1-4). The inventors demonstrate that SRC1-4 is the most potent MR-binding motif and mutations that disrupt the MR/SRC1-4 interactions abolish the ability of the full-length SRC1 to coactivate MR. The structure also reveals a compact steroid binding pocket with a unique topology that is primarily defined by key residues of helices 6 and 7. Also described are novel ligands for MR, methods for screening for and designing novel MR ligands, and methods for treating MR-related diseases.

Abstract: The 1.5 ? crystal structure of the orphan nuclear receptor steroidogenic factor 1 (SF-1) ligand binding domain in complex with an LxxLL motif from a co-regulator protein is disclosed. The structure reveals the presence of a phospholipid ligand in a surprisingly large pocket (˜1600 ?3), with the receptor adopting the canonical active conformation. The bound phospholipid is readily exchanged and modulates SF-1 interactions with co-activators. Directed mutations that alter the ligand binding pocket disrupt SF-1/co-activator interactions and reduce SF-1 transcriptional activity. Also disclosed is a method to screen chemical libraries for compounds with high specificity or binding affinity for SF-1, thereby permitting the discovery of agonist or antagonist drugs useful in treating dyslipidemias and/or in promoting cholesterol homeostasis.

Abstract: A method of modifying a test nuclear receptor (NR) polypeptide is disclosed. The method provides a test NR polypeptide sequence having a characteristic that is targeted for modification; aligning the test NR polypeptide sequence with at least one reference NR polypeptide sequence for which an X-ray structure is available; building a three-dimensional model for the test NR polypeptide using the three-dimensional coordinates of the X-ray structure(s) of at least one reference polypeptide and its sequence alignment with the test NR polypeptide sequence; examining the three-dimensional model of the test NR polypeptide sequence for characteristic differences with the reference polypeptide; and mutating at least one amino acid residue in the test NR polypeptide sequence at a characteristic difference, whereby the test NR polypeptide is modified.