Published in Molecular Pharmacology
Amplification of pro-oncogenic kinases is a common genetic alteration driving tumorigenic phenotypes. Cancer cells rely on the amplified kinases to sustain cell proliferation, survival, and growth, presenting an opportunity to develop therapies targeting the amplified kinases. Utilizing small molecule catalytic inhibitors as therapies to target amp...
Published in Molecular Pharmacology
The mammalian target of rapamycin (mTOR) senses upstream stimuli to regulate numerous cellular functions such as metabolism, growth, and autophagy. Increased activation of mTOR complex 1 (mTORC1) is typically observed in human disease and continues to be an important therapeutic target. Understanding the upstream regulators of mTORC1 will provide a...
Published in Molecular Pharmacology
Calcium- and voltage-gated K+ channels of large conductance (BKs) are expressed in the cell membranes of all excitable tissues. Currents mediated by BK channel-forming slo1 homotetramers are consistently inhibited by increases in membrane cholesterol (CLR). The molecular mechanisms leading to this CLR action, however, remain unknown. Slo1 channels ...
Published in Molecular Pharmacology
Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local and distant metastasis and disease relapse are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces...
Published in Molecular pharmacology
Aberrant dopamine (DA) signaling is associated with several psychiatric disorders, such as autism, bipolar disorder, addiction, and Parkinson's disease, and several medications that target the DA transporter (DAT) can induce or treat these disorders. In addition, psychostimulants, such as cocaine and D-amphetamine (AMPH), rely on the competitive in...
Published in Molecular pharmacology
The GABAA receptor is inhibited by the endogenous sulfated steroids pregnenolone sulfate (PS) and dehydroepiandrosterone sulfate (DHEAS). It has been proposed in previous work that these steroids act by enhancing desensitization of the receptor. Here, we have investigated the modulatory effects of the steroids on the human α1β3γ2L GABAA receptor. U...
Published in Molecular pharmacology
G protein-coupled receptors (GPCRs) transduce a diverse variety of extracellular stimuli into intracellular signaling. These receptors are the most clinically productive drug targets at present. Despite decades of research on the signaling consequences of molecule-receptor interactions, conformational components of receptor-effector interactions re...
Published in Molecular pharmacology
Aryl hydrocarbon receptor (AhR) is a ligand-mediated transcription factor known for regulating response to xenobiotics, including prototypical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the activation of CYP1A1 expression. Upon ligand-binding, AhR translocates to the nucleus, interacts with the AhR nuclear translocator, and binds to xenobio...
Published in Molecular Pharmacology
Published in Molecular Pharmacology
G protein–gated inwardly rectifying K+ (GIRK) channels are critical mediators of excitability in the heart and brain. Enhanced GIRK-channel activity has been implicated in the pathogenesis of supraventricular arrhythmias, including atrial fibrillation. The lack of selective pharmacological tools has impeded efforts to investigate the therapeutic po...
