A process for preparing a compound of Formula (1a):

##STR00001##

or a pharmaceutically acceptable salt thereof.

A process for preparing a compound of Formula (1a):

##STR00001##

or a pharmaceutically acceptable salt thereof.

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.

A composition for preserving viability of cells, tissues, or organs at a low temperature is provided. The composition includes a mitochondrial uncoupling agent, at least one protease inhibitor, and a reducing agent. Methods to protect cells, tissues, or organs from exposure to cold and other metabolic stress are also provided.

A composition for preserving viability of cells, tissues, or organs at a low temperature is provided. The composition includes a mitochondrial uncoupling agent, at least one protease inhibitor, and a reducing agent. Methods to protect cells, tissues, or organs from exposure to cold and other metabolic stress are also provided.

Disclosed herein are methods of treating a subject with an estrogen receptor-positive (ER+) breast cancer comprising obtaining a sample of the breast cancer from the subject; determining a level of E-cadherin in the sample is reduced compared to a control; and administering a therapeutically effective amount of an IGF1R pathway inhibitor and an endocrine therapeutic. Also disclosed herein are methods to treat a cancer in a subject comprising administering a therapeutically effective amount of an IGF1R pathway inhibitor and an E-cadherin inhibitor. Also disclosed are methods to predict the likelihood a subject with a breast cancer will respond therapeutically to a treatment comprising administering an IGF1R pathway inhibitor, the method comprising obtaining a sample of the cancer from the subject; and determining a level of E-cadherin in the sample.

Disclosed herein are methods of treating a subject with an estrogen receptor-positive (ER+) breast cancer comprising obtaining a sample of the breast cancer from the subject; determining a level of E-cadherin in the sample is reduced compared to a control; and administering a therapeutically effective amount of an IGF1R pathway inhibitor and an endocrine therapeutic. Also disclosed herein are methods to treat a cancer in a subject comprising administering a therapeutically effective amount of an IGF1R pathway inhibitor and an E-cadherin inhibitor. Also disclosed are methods to predict the likelihood a subject with a breast cancer will respond therapeutically to a treatment comprising administering an IGF1R pathway inhibitor, the method comprising obtaining a sample of the cancer from the subject; and determining a level of E-cadherin in the sample.

The present application relates to novel compounds of formula (I) ##STR00001##
to their utility in treating and/or preventing clinical conditions including cardiovascular diseases (CVD), to methods for their therapeutic use, to pharmaceutical compositions containing them and to processes for preparing such compounds.

The present application relates to novel compounds of formula (I) ##STR00001##
to their utility in treating and/or preventing clinical conditions including cardiovascular diseases (CVD), to methods for their therapeutic use, to pharmaceutical compositions containing them and to processes for preparing such compounds.