Disulfide-Isomerase A4 (PDIA4) inhibitors and use thereof for inhibiting pancreatic β-cell pathogenesis and treating diabetes are disclosed. Drug candidates that inhibit PDIA4 with IC50 values ranging from 4 μM to 300 nM are identified. The compounds are highly active in augmenting insulin secretion from pancreatic β-cells. The representative compound No. 8 (4,5-dimethoxy-2-propiolamidobenzoic acid), alone or in combination with metformin, is effective in preserving pancreatic β-cell function, treating and/or reversing, returning blood glucose concentration to a normal level in a diabetic.

The present invention relates to a contrast agent suitable for ex vivo imaging, particularly of vascular structures and renal tubular structures, and a method for ex vivo imaging. The contrast agent is a polymer comprising monomers M. The monomer comprises a backbone having 2 to 6 elements, wherein at least one element is —CH(R)— or —N(R)—. R is a moiety -E-H, -L-(NH2)m or a moiety of formula 1, with E, L, R.sup.1 and R.sup.2 being defined as described in the present specification. The monomer comprises at least one —I to allow detection via X-ray and at least one —NH.sub.2 to allow crosslinking. Furthermore, the monomer comprises polar functional groups that contribute to water solubility. To avoid extravasation and glomerular filtration, the polymers are pre-crosslinked before the vasculature of a tissue, an organ or whole animal is perfused. After perfusion, the pre-crosslinked contrast agent is further crosslinked to be retained within the tissue, organ or animal permanently.

The present invention relates to a contrast agent suitable for ex vivo imaging, particularly of vascular structures and renal tubular structures, and a method for ex vivo imaging. The contrast agent is a polymer comprising monomers M. The monomer comprises a backbone having 2 to 6 elements, wherein at least one element is —CH(R)— or —N(R)—. R is a moiety -E-H, -L-(NH2)m or a moiety of formula 1, with E, L, R.sup.1 and R.sup.2 being defined as described in the present specification. The monomer comprises at least one —I to allow detection via X-ray and at least one —NH.sub.2 to allow crosslinking. Furthermore, the monomer comprises polar functional groups that contribute to water solubility. To avoid extravasation and glomerular filtration, the polymers are pre-crosslinked before the vasculature of a tissue, an organ or whole animal is perfused. After perfusion, the pre-crosslinked contrast agent is further crosslinked to be retained within the tissue, organ or animal permanently.

The disclosures herein relate to novel compounds of formula (1): (1) and salts thereof, wherein A, X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.10 and R.sup.11 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with EP.sub.4 receptors.

##STR00001##

The disclosures herein relate to novel compounds of formula (1): (1) and salts thereof, wherein A, X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.10 and R.sup.11 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with EP.sub.4 receptors.

##STR00001##

Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, compositions, and mixtures thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing diseases (e.g., proliferative diseases (e.g., cancers, such as carcinoma, sarcoma, lung cancer, thyroid cancer, skin cancer, ovarian cancer, colorectal cancer, prostate cancer, pancreatic cancer, esophageal cancer, liver cancer, breast cancer)) in a subject. Provided are methods of inhibiting a TEAD transcription factors (e.g., TEAD1, TEAD2, TEAD3, TEAD4) in a subject.

##STR00001##

The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds and methods of making and using such compounds.

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

The invention relates to a compound of formula (I) wherein R.sup.1—R.sup.3 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.

##STR00001##

The invention relates to a compound of formula (I) wherein R.sup.1—R.sup.3 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.

##STR00001##