Knowledge Library
Structure-based optimization of hydroxylactam as potent, cell-active inhibitors of lactate dehydrogenase
Structure-based design was utilized to optimize 6,6-diaryl substituted dihydropyrone and hydroxylactam to obtain inhibitors of lactate dehydrogenase (LDH) with low nanomolar biochemical and single-digit micromolar cellular potencies. Surprisingly the replacement of a phenyl with a pyridyl moiety in the chemical structure revealed a new binding mode for the inhibitors with subtle conformational change of the …Read More >
Drug Discovery: Screening Approaches for Rapid Assessment of Target Tractability
HIJACKING CELLULAR MECHANISMS TO TREAT COMPLEX DISEASES
RARE DISEASES: OPPORTUNITIES AND CHALLENGES FOR TREATMENTS DELIVERED BY ADENO-ASSOCIATED VIRUSES
Optimizing Drug Pipelines With Biophysical Methods
Download our whitepaper on how using biophysical techniques can enhance and streamline processes throughout the drug discovery and validation cycle. Discover fresh opportunities to characterize challenging drug targets, examine biophysical screening methods, and look toward what’s next for biophysical methods in drug discovery.
Brain metastasis mouse models for the evaluation of multikinase inhibitors on ROS1-fusion-positive lung cancer
Lung cancer is the leading cause of cancer-related death worldwide. Nearly 80% of lung cancers are non-small cell lung cancer (NSCLC) and 60% of them are diagnosed at the metastatic stage. Brain metastases affect more than 20% of NSCLC patients with poor prognosis and disabling symptoms. However, few therapies have been approved for the treatment …Read More >
Intra-carotid artery brain metastasis models for the evaluation of lung and breast cancer drugs
Non-CNS metastatic brain cancer is approximately 10 times more common than CNS cancer. Lung cancer and breast cancer account for most brain metastasis. KRAS-mutant NSCLC composes a third lung adenocarcinoma, among which 17% to 55% will develop brain metastases. Likewise, more than a third HER2-positive breast cancer will develop brain metastasis. Among existing animal models, …Read More >
Developing drug-induced resistant tumor models for efficacy evaluation of next-generation anticancer therapies
The therapeutic landscape of cancer has been transformed over the last few decades. Our understanding of cancer and its therapeutic approach has improved greatly due to advanced cancer biology, functional imaging and next–generation sequencing. One of the key challenges in cancer therapy is how to effectively kill cancer cells while leaving normal cells intact. As …Read More >
Developing a panel of orthotopic syngeneic tumor models for IO drug discovery
The efficacy of immuno-oncology therapies needs to be evaluated in animal models with functional immune systems. Syngeneic tumor models are established by inoculating mouse cancer cell lines into immunocompetent mice with the same genetic background. The host mice have complete immune activity and show histocompatibility with homograft tumor tissues, which can maximize the simulation of …Read More >
