解剖学和形态学
麻醉学
听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
免疫学
传染病
综合和补充性医学
医学伦理学
医学信息学
医学实验室技术
医学,全科和内科
医学,法律
医学,研究和试验
神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
肿瘤学
眼科学
整形外科学
耳鼻喉科学
病理学
儿科学
周围血管疾病
药理学和药剂学
生理学
基本医疗保健
精神病学
公共、环境和职业卫生
放射学,核医学和医学成像
康复学
生殖生物学
呼吸系统
风湿病学
运动科学
外科学
毒理学
热带医学
泌尿学和肾脏学
病毒学
老年医学
健康政策和服务
心理学,临床
abstract::Equilibrative nucleoside transporters (ENTs) 1 and 2 facilitate nucleoside transport across the blood-testis barrier (BTB). Improving drug entry into the testes with drugs that use endogenous transport pathways may lead to more effective treatments for diseases within the reproductive tract. In this study, CRISPR/CRIS...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/molpharm.120.000169
更新日期:2021-02-01 00:00:00
abstract::Benzbromarone (BBR), a potent uricosuric agent for the management of gout, is known to cause fatal fulminant hepatitis. While the mechanism of BBR-induced idiosyncratic hepatotoxicity remains unelucidated, cytochrome P450 enzyme (CYP450)-mediated bioactivation of BBR to electrophilic reactive metabolites is commonly r...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/molpharm.120.000086
更新日期:2021-01-12 00:00:00
abstract::Voltage-gated sodium channels (Navs) are promising targets for analgesic and antiepileptic therapies. Although specificity between Nav subtypes may be desirable to target specific neural types, such as nociceptors in pain, many broadly acting Nav inhibitors are clinically beneficial in neuropathic pain and epilepsy. H...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/molpharm.120.000079
更新日期:2021-01-01 00:00:00
abstract::Advances in proteomic methodologies based on quantitative mass spectrometry are now transforming pharmacology and experimental biology more broadly. The present review will discuss several examples, based on work in the author's laboratory that focuses on delineating relationships between GPCR signaling and traffickin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/molpharm.120.000178
更新日期:2020-12-22 00:00:00
abstract::Regulator of G protein signaling (RGS) proteins are negative modulators of G protein signaling that have emerged as promising drug targets to improve specificity and reduce side effects of G protein-coupled receptor-related therapies. Several small molecule RGS protein inhibitors have been identified; however, enhanci...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/molpharm.120.000061
更新日期:2020-12-01 00:00:00
abstract::The Notch family consists of four highly conserved transmembrane receptors. The release of the active intracellular domain requires the enzymatic activity of γ-secretase. Notch is involved in embryonic development and in many physiologic processes of normal cells, in which it regulates growth, apoptosis, and different...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/molpharm.120.000006
更新日期:2020-11-01 00:00:00
abstract::The human CYP2C9 plays a crucial role in the metabolic clearance of a wide range of clinical therapeutics. The *2 allele is a prevalent genetic variation in CYP2C9 that is found in various populations. A marked reduction of catalytic activity toward many important drug substrates has been demonstrated by CYP2C9*2, whi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/molpharm.120.000042
更新日期:2020-11-01 00:00:00
abstract::The μ-opioid receptor gene undergoes extensive alternative splicing to generate an array of splice variants. One group of splice variants excludes the first transmembrane (TM) domain and contains six TM domains. These 6TM variants are essential for the action of a novel class of analgesic drugs, including 3-iodobenzoy...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.120.119453
更新日期:2020-10-01 00:00:00
abstract::The powerful analgesic effects of opioid drugs have captivated the interest of physicians and scientists for millennia, and the ability of opioid drugs to produce serious undesired effects has been recognized for a similar period of time (Kieffer and Evans, 2009). Many of these develop progressively with prolonged or ...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.119.119321
更新日期:2020-10-01 00:00:00
abstract::Several reports have been published recently demonstrating a beneficial effect of epidermal growth factor receptor (EGFR) inhibitors in improving pathologic and behavioral conditions in neurodegenerative diseases (NDDs) such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS) as well as the brain and spinal...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.120.119909
更新日期:2020-07-01 00:00:00
abstract::The microtubule-binding taxanes, docetaxel and cabazitaxel, are administered intravenously for the treatment of castration-resistant prostate cancer (CRPC) as the oral administration of these drugs is largely hampered by their low and highly variable bioavailabilities. Using a simple, rapid, and environmentally friend...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.118539
更新日期:2020-06-01 00:00:00
abstract::G protein-coupled receptor (GPCR) kinases (GRKs) play a key role in terminating signals initiated by agonist-bound GPCRs. However, chronic stimulation of GPCRs, such as that which occurs during heart failure, leads to the overexpression of GRKs and maladaptive downregulation of GPCRs on the cell surface. We previously...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.118661
更新日期:2020-06-01 00:00:00
abstract::Dysfunction of p53 and resistance to cancer drugs can arise through mutually exclusive overexpression of MDM2 or MDM4. Cisplatin-resistant cells, however, can demonstrate increased binding of both MDM2 and MDM4 to p53 but in absence of cellular overexpression. Whether MDM2 inhibitors alone can activate p53 in these re...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.117564
更新日期:2020-04-01 00:00:00
abstract::By limiting unrestricted activation of intracellular effectors, compartmentalised signalling of cyclic nucleotides confers specificity to extracellular stimuli and is critical for the development and health of cells and organisms. Dissecting the molecular mechanisms that allow local control of cyclic nucleotide signal...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.118869
更新日期:2020-02-28 00:00:00
abstract::The class Frizzled (FZD) or class F of G protein-coupled receptors consists of 10 FZD paralogues and Smoothened (SMO). FZDs coordinate wingless/Int-1 signaling and SMO mediates Hedgehog signaling. Class F receptor signaling is intrinsically important for embryonic development and its dysregulation leads to diseases, i...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.119.117986
更新日期:2020-02-01 00:00:00
abstract::Recent reports regarding the significance of chemokine receptors in disease have put a spotlight on atypical chemokine receptor 3 (ACKR3). This atypical chemokine receptor is overexpressed in numerous cancer types and has been involved in the modulation of tumor cell proliferation and migration, tumor angiogenesis, or...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.118.115279
更新日期:2019-12-01 00:00:00
abstract::Chemokine receptors belong to the class A of G protein-coupled receptors (GPCRs) and are implicated in a wide variety of physiologic functions, mostly related to the homeostasis of the immune system. Chemokine receptors are also involved in multiple pathologic processes, including immune and autoimmune diseases, as we...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.119.117168
更新日期:2019-12-01 00:00:00
abstract::Dysregulation of the chemokine system is implicated in a number of autoimmune and inflammatory diseases, as well as cancer. Modulation of chemokine receptor function is a very promising approach for therapeutic intervention. Despite interest from academic groups and pharmaceutical companies, there are currently few ap...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.119.116954
更新日期:2019-12-01 00:00:00
abstract::The two G protein-coupled receptors (GPCRs) C-X-C chemokine receptor type 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are part of the class A chemokine GPCR family and represent important drug targets for human immunodeficiency virus (HIV) infection, cancer, and inflammation diseases. CXCR4 is one of only thre...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.119.117663
更新日期:2019-12-01 00:00:00
abstract::The tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a vascular endothelial growth factor (VEGF) receptor-2 antagonist, has been used previously either alone or in combination with chemotherapeutic drugs for treating colorectal cancer in a mouse model. We analyzed the half-life of the peptide and found that because of degradation...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.117234
更新日期:2019-12-01 00:00:00
abstract::Aldehyde hydrogenases (ALDHs) belong to a large gene family involved in oxidation of both endogenous and exogenous compounds in mammalian tissues. Among ALDHs, the rat ALDH1A7 gene displays a curious strain dependence in phenobarbital (PB)-induced hepatic expression: the responsive RR ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.117424
更新日期:2019-11-01 00:00:00
abstract::The ligand-binding sites of many G protein-coupled receptors (GPCRs) are situated around and deeply embedded within the central pocket formed by their seven transmembrane-spanning α-helical domains. Generally, these binding sites are assumed accessible to endogenous ligands from the aqueous phase. Recent advances in t...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.118.115113
更新日期:2019-11-01 00:00:00
abstract::ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modes...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.117143
更新日期:2019-10-01 00:00:00
abstract::Diltiazem is a widely prescribed Ca2+ antagonist drug for cardiac arrhythmia, hypertension, and angina pectoris. Using the ancestral CaV channel construct CaVAb as a molecular model for X-ray crystallographic analysis, we show here that diltiazem targets the central cavity of the voltage-gated Ca2+ channel underneath ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.117531
更新日期:2019-10-01 00:00:00
abstract::Molecular chaperone heat shock protein 90 (HSP90) is involved in oncogenic signaling pathways including epithelial-mesenchymal transition (EMT), a key process in tumor initiation, progression, metastasis, and chemoresistance. The molecular mechanisms underlying the involvement of HSP90 in EMT are still under investiga...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.116137
更新日期:2019-08-01 00:00:00
abstract::Circular RNAs (circRNAs) are a distinct category of single-stranded, covalently closed RNAs formed by backsplicing. The functions of circRNAs are incompletely known and are under active investigation. Here, we report that in addition to traditional linear mRNAs (linRNA), mouse, rat, and human opioid receptor genes gen...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.113977
更新日期:2019-08-01 00:00:00
abstract::Pancreatic cancer is one of the most lethal types of tumors with no effective therapy available; is currently the third leading cause of cancer in developed countries; and is predicted to become the second deadliest cancer in the United States by 2030. Due to the marginal benefits of current standard chemotherapy, the...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.115444
更新日期:2019-07-01 00:00:00
abstract::Westernization of dietary habits increases lipid intake and is responsible for increased numbers of patients with atherosclerotic diseases. Niemann-Pick C1-Like 1 (NPC1L1)-a cholesterol importer-plays a crucial role in dietary cholesterol absorption in the intestine and is closely associated with several lipid-related...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.115840
更新日期:2019-07-01 00:00:00
abstract::Propofol, etomidate, and barbiturate anesthetics are allosteric coagonists at pentameric α1β3γ2 GABAA receptors, modulating channel activation via four biochemically established intersubunit transmembrane pockets. Etomidate selectively occupies the two β+/α- pockets, the barbiturate photolabel R-5-allyl-1-methyl-5-(m-...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.115048
更新日期:2019-04-01 00:00:00
abstract::AM1710 (3-(1,1-dimethyl-heptyl)-1-hydroxy-9-methoxy-benzo(c) chromen-6-one), a cannabilactone cannabinoid receptor 2 (CB2) agonist, suppresses chemotherapy-induced neuropathic pain in rodents without producing tolerance or unwanted side effects associated with CB1 receptors; however, the signaling profile of AM1710 re...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.113233
更新日期:2019-02-01 00:00:00
abstract::The inflammatory response is necessary for the host's defense against pathogens; however, uncontrolled or unregulated production of eicosanoids has been associated with several types of chronic inflammatory diseases. Thus, it is not surprising that enzymes implicated in the production of eicosanoids have been strategi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.113480
更新日期:2019-01-01 00:00:00
abstract::Lysosomes degrade cellular proteins and organelles and regulate cell signaling by providing a surface for the formation of critical protein complexes, notably molecular target of rapamycin (mTOR) complex 1 (mTORC1). Striking differences in the lysosomes of cancer versus normal cells suggest that they could be targets ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.113118
更新日期:2019-01-01 00:00:00
abstract::Schizophrenia (SZ), schizoaffective (SZA), and bipolar (BP) disorder are neurodevelopmental psychopathological conditions related, in part, to genetic load and, in part, to environmentally induced epigenetic dysregulation of chromatin structure and function in neocortical GABAergic, glutamatergic, and monoaminergic ne...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.113415
更新日期:2019-01-01 00:00:00
abstract::5-Hydroxytryptamine3 (5-HT3) receptors are ligand-gated ion channels that mediate neurotransmission by serotonin in the central nervous system. Pharmacological inhibition of 5-HT3 receptor activity has therapeutic potential in several psychiatric diseases, including depression and anxiety. The recently approved multim...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.113530
更新日期:2018-12-01 00:00:00
abstract::Combining chemotherapeutics to treat malignant tumors has been shown to be effective in preventing drug resistance, tumor recurrence, and reducing tumor size. We modeled combination drug therapy in PC-3 human prostate cancer cells using mixture design response surface methodology (MDRSM), a statistical technique desig...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.111450
更新日期:2018-08-01 00:00:00
abstract::Glutamatergic synaptic transmitters are cleared from the synaptic cleft through excitatory amino acid transporters (EAATs) that are responsible for recycling glutamate and transporting it into neurons and glial cells. To probe the structural role of the TM4b-4c loop of EAAT1 (Rattus norvegicus), each of the 57 amino a...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.111245
更新日期:2018-07-01 00:00:00
abstract::Cytochrome P450 (P450) enzymes are responsible for metabolizing drugs. Expression of P450s can directly affect drug metabolism, resulting in various outcomes in therapeutic efficacy and adverse effects. Several nuclear receptors are transcription factors that can regulate expression of P450s at both basal and drug-ind...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.112235
更新日期:2018-07-01 00:00:00
abstract::The retinoid (visual) cycle consists of a series of biochemical reactions needed to regenerate the visual chromophore 11-cis-retinal and sustain vision. Genetic or environmental factors affecting chromophore production can lead to blindness. Using animal models that mimic human retinal diseases, we previously demonstr...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.111294
更新日期:2018-05-01 00:00:00
abstract::Glutathione-liganded binuclear dinitrosyl iron complex (glut-BDNIC) has been proposed to be a donor of nitric oxide (NO). This study was undertaken to investigate the mechanisms of vasoactivity, systemic hemodynamic effects, and pharmacokinetics of glut-BDNIC. To test the hypothesis that glut-BDNICs vasodilate by rele...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.110957
更新日期:2018-05-01 00:00:00
abstract::Caveolins have been recognized over the past few decades as key regulators of cell physiology. They are ubiquitously expressed and regulate a number of processes that ultimately impact efficiency of cellular processes. Though not critical to life, they are central to stress adaptation in a number of organs. The follow...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.117.111237
更新日期:2018-04-01 00:00:00