The disclosure relates to substituted fused heteroaromatic tricyclic compounds and the use thereof. Specifically, the disclosure provides compounds of the following Formula I: ##STR00001##
or a pharmaceutically acceptable salt or prodrug thereof, wherein A.sub.1-A.sub.3, B.sub.1-B.sub.3, D.sub.1-D.sub.4 and R.sub.1-R.sub.2 are defined herein. Compounds having Formula I are ATM kinase inhibitors. Therefore, compounds of the disclosure may be used to treat clinical conditions caused by DDR functional defects, such as cancer.

The disclosure relates to substituted fused heteroaromatic tricyclic compounds and the use thereof. Specifically, the disclosure provides compounds of the following Formula I: ##STR00001##
or a pharmaceutically acceptable salt or prodrug thereof, wherein A.sub.1-A.sub.3, B.sub.1-B.sub.3, D.sub.1-D.sub.4 and R.sub.1-R.sub.2 are defined herein. Compounds having Formula I are ATM kinase inhibitors. Therefore, compounds of the disclosure may be used to treat clinical conditions caused by DDR functional defects, such as cancer.

The present disclosure relates to a medicament for treating cholangiocarcinoma with KRAS mutations. Specifically, the present invention relates to a method of ER inhibitors for the specific treatment of cholangiocarcinoma with KRAS mutations, and to a use of ER inhibitors in the preparation of a medicament for the treatment of cholangiocarcinoma with KRAS mutations. New therapeutic regimens for patients suffering from cholangiocarcinoma with KRAS mutations are provided to improve the possibility of therapeutic benefit for patients.

The present disclosure relates to a medicament for treating cholangiocarcinoma with KRAS mutations. Specifically, the present invention relates to a method of ER inhibitors for the specific treatment of cholangiocarcinoma with KRAS mutations, and to a use of ER inhibitors in the preparation of a medicament for the treatment of cholangiocarcinoma with KRAS mutations. New therapeutic regimens for patients suffering from cholangiocarcinoma with KRAS mutations are provided to improve the possibility of therapeutic benefit for patients.

The present disclosure is directed to methods of treating a steatosis-associated disorder by administering a therapeutic agent selected from a lysosomal enzyme, an autophagy-inducing agent, or a combination thereof. Steatosis-associated disorders discussed herein include GSD Ia, GSD Ib, GSD Ic, NAFLD, and NASH. Other embodiments are directed to methods of reversing steatosis, modulating autophagy, inducing autophagy, and reversing glycogen storage.

The present disclosure is directed to methods of treating a steatosis-associated disorder by administering a therapeutic agent selected from a lysosomal enzyme, an autophagy-inducing agent, or a combination thereof. Steatosis-associated disorders discussed herein include GSD Ia, GSD Ib, GSD Ic, NAFLD, and NASH. Other embodiments are directed to methods of reversing steatosis, modulating autophagy, inducing autophagy, and reversing glycogen storage.

It is intended to provide a novel method for treating a cancer using an FGFR inhibitor that exhibits a remarkably excellent antitumor effect and has fewer side effects. The present invention provides a combination preparation for the treatment of a malignant tumor comprising a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, and one or more additional compound(s) having an antitumor effect or pharmaceutically acceptable salt(s) thereof, and a pharmaceutical composition comprising both the active ingredients. The present invention also provides an antitumor effect enhancer, an antitumor agent, a kit for malignant tumor treatment, etc. comprising a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof.

A medicine for improving the state of pregnancy, which comprises a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient; and a use of the medicine.

A medicine for improving the state of pregnancy, which comprises a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient; and a use of the medicine.

Disclosed herein are nerve xenografts and methods of using such for repairing and/or protecting a nerve tissue in a human patient. The subject matter disclosed herein generally relates to nerve xenografts derived from genetically engineered source animals, and use of such nerve xenografts for repairing and/protecting nerve tissue in a human patient, e.g., for reconstruction of large peripheral nerve gaps, treatment of spinal cord injuries and ailments, and other therapies.