Provided herein are small molecule inhibitors for the targeting or IRE1 protein family members. Binding may be direct or indirect. Further provided herein are methods of using IRE1 small molecule inhibitors for use in treating or ameliorating cancer in a subject. Moreover, IRE1 small molecule inhibitors described herein are for the treatment of cancer, where the cancer is a solid or hematologic cancer.

Disclosed is a fused ring compound and an application thereof. Disclosed is a fused ring compound represented by formula I, a pharmaceutically acceptable salt, a stereoisomer, a tautomer, an isotope compound, a crystal form, a nitrogen oxide, a solvate, or a solvate of the pharmaceutically acceptable salt thereof. The fused ring compound of the present invention has high P2X4 antagonistic activity, excellent selectivity, low toxicity and excellent metabolic stability.

##STR00001##

Chemical entities that are kinase inhibitors, their polymorphs, pharmaceutical compositions and methods of treatment of cancer are described herein.

Chemical entities that are kinase inhibitors, their polymorphs, pharmaceutical compositions and methods of treatment of cancer are described herein.

Provided herein are small molecule inhibitors for the targeting or IRE1 protein family members. Binding may be direct or indirect. Further provided herein are methods of using IRE1 small molecule inhibitors for use in treating or ameliorating cancer in a subject. Moreover, IRE1 small molecule inhibitors described herein are for the treatment of cancer, where the cancer is a solid or hematologic cancer.

Provided herein are small molecule inhibitors for the targeting or IRE1 protein family members. Binding may be direct or indirect. Further provided herein are methods of using IRE1 small molecule inhibitors for use in treating or ameliorating cancer in a subject. Moreover, IRE1 small molecule inhibitors described herein are for the treatment of cancer, where the cancer is a solid or hematologic cancer.

Disclosed herein, inter alia, are inhibitors of alpha 2 beta 1 integrin and methods of using the same.

Disclosed herein, inter alia, are inhibitors of alpha 2 beta 1 integrin and methods of using the same.

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): ##STR00001##
or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R.sup.1, R.sup.2a, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): ##STR00001##
or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R.sup.1, R.sup.2a, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, G.sup.1, G.sup.2, L.sup.1, L.sup.2, m.sup.1, m.sup.2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.