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 approved medicines targeting chemokine receptors. Monoclonal antibodies (mAbs) and antibody-based molecules have been successfully applied in the clinical therapy of cancer and represent a potential new class of therapeutics targeting chemokine receptors belonging to the class of G protein-coupled receptors (GPCRs). Besides conventional mAbs, single-domain antibodies and antibody scaffolds are also gaining attention as promising therapeutics. In this review, we provide an extensive overview of mAbs, single-domain antibodies, and other antibody fragments targeting CXCR4 and ACKR3, formerly referred to as CXCR7. We discuss their unique properties and advantages over small-molecule compounds, and also refer to the molecules in preclinical and clinical development. We focus on single-domain antibodies and scaffolds and their utilization in GPCR research. Additionally, structural analysis of antibody binding to CXCR4 is discussed. SIGNIFICANCE STATEMENT: Modulating the function of GPCRs, and particularly chemokine receptors, draws high interest. A comprehensive review is provided for monoclonal antibodies, antibody fragments, and variants directed at CXCR4 and ACKR3. Their advantageous functional properties, versatile applications as research tools, and use in the clinic are discussed.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Bobkov V,Arimont M,Zarca A,De Groof TWM,van der Woning B,de Haard H,Smit MJdoi
10.1124/mol.119.116954subject
Has Abstractpub_date
2019-12-01 00:00:00pages
753-764issue
6eissn
0026-895Xissn
1521-0111pii
mol.119.116954journal_volume
96pub_type
杂志文章,评审abstract：:The chemical reaction of 1,4-benzoquinone with glutathione results in the formation of adducts that exhibit increasing degrees of glutathione substitution. Purification of these adducts and analysis by 1H and 13C nuclear magnetic resonance spectroscopy revealed the products of the reaction to be 2-(glutathion-S-yl)hyd...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:Folate receptor-targeted cancer therapies constitute a promising treatment for the approximately one third of human cancers that overexpress the folate receptor (FR). However, the potencies of all folate-receptor targeted therapies depend on 1) the rate of folate-linked drug conjugate binding to the cancer cell surfac...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.003723
更新日期：2004-12-01 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：:Cultured murine hepatoma 1c1c7 cells were treated with either the actin filament-disrupting drug cytochalasin D or the microtubule inhibitors colchicine and nocadazole (NOC) to assess the role of the cytoskeleton in the process of cytochrome P450 Cyp1a-1 induction. Indirect fluorescence analyses demonstrated that micr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:Aldosterone synthase (AS) regulates blood volume by synthesizing the mineralocorticoid aldosterone. Overproduction of aldosterone in the adrenal gland can lead to hypertension, a major cause of heart disease and stroke. Aldosterone production depends upon stimulation of AS expression by the renin-angiotensin system, w...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.076471
更新日期：2012-03-01 00:00:00
abstract：:Cholinesterase inhibitors are commonly used to improve cognition and treat psychosis and other behavioral symptoms in Alzheimer's disease, Parkinson's disease, and other neuropsychiatric conditions. However, mechanisms may exist that down-regulate the synaptic response to altered cholinergic transmission, thus limitin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.6.1309
更新日期：2003-12-01 00:00:00
abstract：:Microglia, as phagocytes and antigen-presenting cells in the central nervous system, are activated in such disease processes as stroke and multiple sclerosis. Because peripheral macrophages are capable of producing endocannabinoids, we have examined endocannabinoid production in a macrophage-colony stimulating factor ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.65.4.999
更新日期：2004-04-01 00:00:00
abstract：:The constitutive androstane receptor (CAR) regulates mouse and human CYP2B genes through binding to the direct repeat-4 (DR4) motifs present in the phenobarbital-responsive enhancer module (PBREM). The preference of PBREM elements for nuclear receptors and the extent of cross-talk between CAR and other nuclear recepto...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.2.366
更新日期：2002-08-01 00:00:00
abstract：:Glucose utilization in isolated islets of Langerhans of the rat was determined by measuring the conversion of [5-3H]glucose (10 mM) to 3H2O. The alpha 2-adrenoceptor agonists clonidine, epinephrine, and norepinephrine in the presence of the alpha 1-adrenoceptor antagonist prazosin and the beta-adrenoceptor antagonist ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
abstract：:To screen for residues of hKv1.3 important for current block by the phenylalkylamine verapamil, the inactivated-state-reduced H399T mutant was used as a background for mutagenesis studies. This approach was applied mainly to abolish the accumulation in the inactivated blocked state, recovery from which in the wild typ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.012401
更新日期：2005-10-01 00:00:00
abstract：:Metabolism of the pulmonary toxin, 4-ipomeanol, in microsomal preparations from rabbit liver and lung and in purified cytochrome P-450-dependent monooxygenase systems was investigated. The rate of formation of reactive electrophilic products from 4-ipomeanol was estimated by measuring covalent binding to protein or gl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
abstract：:The relationship between the phospholipase-stimulating and immunosuppressive properties of cyclosporin A (CsA) has been investigated in vitro. At concentrations of 0.025 microM and upwards, CsA caused dose-related inhibition of both mitogen- and alloantigen-stimulated uptake of tritiated thymidine by human mononuclear...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:In the present study, we have elucidated the functional characteristics and mechanism of action of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone, Quaalude), an infamous sedative-hypnotic and recreational drug from the 1960s-1970s. Methaqualone was demonstrated to be a positive allosteric modulator at human α1,2...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.099291
更新日期：2015-08-01 00:00:00
abstract：:We investigated the roles of cyclic GMP and cyclic AMP in the inhibition of rabbit platelet aggregation and degranulation by two nitrovasodilators, sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1; the active metabolite of molsidomine), with particular reference to the synergistic interaction of these dru...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:A1 adenosine receptors in bovine cerebral cortex have been solubilized and subjected to sedimentation analysis using sucrose density gradient centrifugation. Because the receptors bound both agonists and antagonists with high affinity after solubilization, receptors labeled with an agonist or an antagonist radioligand...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：:The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression pattern...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.101808
更新日期：2016-04-01 00:00:00
abstract：:Freshly isolated rat hepatocytes rapidly lose their cytochrome P450 (P450) proteins and mRNAs, with no evidence of subsequent restoration, after placement into traditional systems of primary culture on type I collagen. We examined the patterns of expression of 10 constitutively expressed P450 mRNAs in rat hepatocytes ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:The regulation of cellular responsiveness to dopamine via the D2 dopamine receptor was investigated in mouse fibroblast Ltk-cells stably expressing the rat D2-short receptor [Nature (Lond.) 336:783-787 (1988)]. Dopamine inhibited forskolin-stimulated cAMP levels in these cells (half-maximal inhibition at 3.9 +/- 1.1 n...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:Although the thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well established agents for the treatment of leukemia, controversies remain regarding their main mode of action. Previous evidence has suggested that although 6-TG exerts a cytotoxic effect through incorporation of 6-thioguanine nucleot...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.1.102
更新日期：2002-07-01 00:00:00
abstract：:The response of myeloid leukemia cells to treatment with 1-beta-D-arabinofuranosylcytosine (ara-C) includes activation of the c-Abl protein tyrosine kinase and the stress-activated protein kinase (SAPK). The present studies demonstrate that treatment of human U-937 leukemia cells with ara-C is associated with transloc...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.6.1489
更新日期：2002-06-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.078683
更新日期：2012-10-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.053629
更新日期：2009-04-01 00:00:00
abstract：:Increasing data indicate that brain endocannabinoid system plays a role in the effects of antidepressant medications. Here we examined the effect of in vivo exposure to the selective serotonin uptake inhibitor fluoxetine on cannabinoid type 1 (CB(1)) receptor density and functionality in the rat prefrontal cortex (PFC...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.060079
更新日期：2010-03-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:The binding of [3H]quinuclidinyl benzilate ([3H]QNB) to cardiac muscarinic receptors was inhibited not only by classical muscarinic antagonists but also by nicotinic blocking agents and inhibitors of acetylcholinesterase. Gallamine, pancuronium, ambenonium, and decamethonium were the most potent of these agents examin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-07-01 00:00:00
abstract：:We reported earlier that delta 9-tetrahydrocannabinol (THC), the main psychoactive ingredient in marihuana, increased markedly the level of unesterified arachidonic acid (AA) in guinea pig cerebral cortex slices prelabeled with [14C]AA. The purpose of the present study was to clarify the mechanism underlying THC-enhan...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:The metabotropic glutamate 5 receptor and the cannabinoid type 1 receptor are G protein-coupled receptors that are widely expressed in the central nervous system. Metabotropic glutamate 5 receptors, present at the postsynaptic site, are coupled to Gαq/11 proteins and display an excitatory response upon activation, whe...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.116.104372
更新日期：2016-11-01 00:00:00
abstract：:The role of mitogen-activated protein kinase signaling and the transcription factor c-Jun in epidermal growth factor (EGF)-induced expression of 12-lipoxygenase in human epidermoid carcinoma A431 cells was studied. EGF increased the activation of extracellular signal-regulated kinase (ERK) and c-Jun amino terminal kin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-01-01 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：:All five (m1-m5) muscarinic receptors are sensitive to allosteric regulation, but gallamine is considerably more potent in slowing the dissociation of N-[3H]methylscopolamine (NMS) from the m2 subtype than from the m3 or m5 subtypes. To study the structural basis for the preference of gallamine for the m2 subtype, we ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
