Related Experiment Video
Updated: Jul 10, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Novel pyrazolo[1,5-a]pyrimidines as c-Src kinase inhibitors that reduce IKr channel blockade
Harunobu Mukaiyama1, Toshihiro Nishimura, Satoko Kobayashi
1Central Research Laboratory, Kissei Pharmaceutical Company Ltd, 4365-1, Azumino-city, Nagano 399-8304, Japan. harunobu_mukaiyama@pharm.kissei.co.jp
Abstract:
To improve the in vitro potency of the c-Src inhibitor 1a and to address its hERG liability, a structure-activity study was carried out, focusing on two regions of the lead compound. The blockade of the delayed cardiac current rectifier K(+) (I(Kr)) channel was overcome by replacing the ethylenediamino group with an amino alcohol group at the 7-position. In addition, modifying the substituents at the 5-position and the side chain groups on the amino alcohols at the 7-position enhanced the intracellular c-Src inhibitory activity and increased central nervous system (CNS) penetration. In the present study, 6l exhibited significant in vivo efficacy in a middle cerebral artery (MCA) occlusion model in rats.
Related Concept Videos
Inhibition of Cdk Activity
Inhibition of CDK Activity
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
Antiviral Nucleoside Inhibitors
Targeted Cancer Therapies
There are several types of targeted therapies against specific...