A5088804767- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Lymphoma Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Neurotransmitter Receptor Influence on Behavior
- Monoclonal and Polyclonal Antibodies Research
- Neuroscience and Neuropharmacology Research
- Analytical Chemistry and Chromatography
- Adenosine and Purinergic Signaling
- Pharmacological Receptor Mechanisms and Effects
- Chemical Synthesis and Analysis
- Ion channel regulation and function
- Nuclear Receptors and Signaling
- Pharmacological Effects of Natural Compounds
- Synthesis and Biological Evaluation
- Cancer-related gene regulation
- Cytokine Signaling Pathways and Interactions
- Endometriosis Research and Treatment
- Estrogen and related hormone effects
- Hypothalamic control of reproductive hormones
- Phytoestrogen effects and research
- Bipolar Disorder and Treatment
- Quinazolinone synthesis and applications
- Obsessive-Compulsive Spectrum Disorders
- Chemical Reaction Mechanisms
Sutro Biopharma (United States)
2016-2023
Roche (United States)
2010-2014
Roche (Switzerland)
1995-2012
Inflammation Research Foundation
2010
Jazz Pharmaceuticals (United States)
2008
University of California, Irvine
1998
CNS Research (United States)
1998
Oregon Health & Science University
1992-1994
Portland VA Medical Center
1989-1991
A heptadecapeptide was identified and purified from porcine brain tissue as a ligand for an orphan heterotrimeric GTP- binding protein (G protein)- coupled receptor (LC132) that is similar in sequence to opioid receptors. This peptide, orphanin FQ, has primary structure reminiscent of peptides. Nanomolar concentrations FQ inhibited forskolin-stimulated adenylyl cyclase activity cells transfected with LC132. inhibitory not affected by the addition ligands, nor did peptide activate Orphanin...
The heptadecapeptide orphanin FQ (OFQ) is a recently discovered neuropeptide that exhibits structural features reminiscent of the opioid peptides and an endogenous ligand to G protein-coupled receptor sequentially related receptors. We have cloned both human rat cDNAs encoding OFQ precursor proteins, investigate whether sequence relationships existing between systems are also found at polypeptide level, in particular would encode several bioactive as do precursors, study regional...
An aspartate residue corresponding to aspartate-80 of dopamine D2 receptors is strictly conserved among that couple guanine nucleotide-binding proteins. Mutation this alters the function several classes neurotransmitter receptors. Dopamine protein Gi inhibit adenylyl cyclase (ATP-pyrophosphate-lyase, cyclizing; EC 4.6.1.1). Like other Gi-coupled receptors, binding agonists and some antagonists sensitive pH sodium. In present report, we demonstrate substitution an alanine or glutamate for...
A human dopamine transporter cDNA was cloned and transfected into COS-7 cells, a cell line that lacks vesicular storage release mechanisms. Cells expressing the acquired capacity to take up via transporter. Ionic conditions stimulate inside-out transport in vivo, such as depolarizing concentrations of K+ or low extracellular Na+, were found Ca(2+)-independent [3H]dopamine from cells. Dopamine uptake inhibitors had one three effects on transporter-mediated efflux. Some drugs, addition...
Abstract: Four dopamine D2 receptor mutants were constructed, in each of which an alanine residue was substituted for one four conserved serine residues, i.e., Ser‐193, Ser‐194, Ser‐197, and Ser‐391. Wild‐type mutant receptors expressed transiently COS‐7 cells stably C6 glioma analysis ligand‐receptor interactions. In radioligand binding assays, the affinity decreased 50‐fold by substitution implicating this dopamine. Each had smaller decreases or more ligands tested, with no apparent...
Purinoceptors containing the P2X3 subunit (P2X3 homotrimeric and P2X2/3 heterotrimeric) are members of P2X family ion channels gated by ATP may participate in primary afferent sensitization a variety pain-related diseases. The current work describes vitro pharmacological characteristics AF-353, novel, orally bioavailable, highly potent selective P2X3/P2X2/3 receptor antagonist.The antagonistic potencies (pIC(50)) AF-353 for rat human receptors were determined using methods radioligand...
STRO-002 is a novel homogeneous folate receptor alpha (FolRα) targeting antibody-drug conjugate (ADC) currently being investigated in the clinic as treatment for ovarian and endometrial cancers. Here, we describe discovery, optimization, antitumor properties of STRO-002. was generated by conjugation cleavable 3-aminophenyl hemiasterlin linker-warhead (SC239) to nonnatural amino acid para-azidomethyl-L-phenylalanine incorporated at specific positions within high affinity anti-FolRα antibody...
Strict pharmacological selectivity in families of structurally related ligands and receptors may result from a key process evolution aiming at increasing diversity neurotransmission. An intriguing example such exclusive specificity can be found the newly discovered orphanin FQ (OFQ) system when it is compared with opioid system. Both OFQ its receptor share high degree sequence similarity to peptides their corresponding receptors, respectively. However, does not activate nor do elicit...
The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members this class may modulate disease activity progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, good biopharmaceutical properties. Evaluation analogue cellular vivo models confirmed functional modulation JAK3/JAK1-dependent...
Comparative analysis has long been utilized in biological research to interpret protein interactions both drug naïve versus challenged and normal diseased tissues. The technology of proteomics today allows researchers provide insight into old still open questions related mechanisms while offering the opportunity discover novel details cellular lifecycles. Perhaps most powerful way execute these differential displays is combination two-dimensional (2-D) gel electrophoresis mass spectrometry....
1. The binding of the new selective group II metabotropic glutamate receptor radioligand, [3H]-(2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine ([3H]-DCG IV), was characterized in rat mGlu2 receptor-transfected CHO cell membranes. 2. [3H]-DCG IV pH-dependent, but not sensitive to temperature. Saturation analysis showed presence a single site, with Kd value 160 nM and Bmax 10 pmol mg(-1) protein. Binding Na+-dependent uptake blockers or Cl-dependent inhibitors. Furthermore, up...
We recently cloned a complementary DNA for the rat dopamine D-2 receptor, making it possible to create cell lines expressing this receptor. A line (LZR1) was created by transfecting cDNA (RGB-2) into mouse fibroblast Ltk- cells. LZR1 cells, previously described as L-RGB2Zem-1 express high density of receptors, whereas wild-type cells do not. number agonists competitively and stereoselectively inhibited binding [3H]spiroperidol expressed receptors in GTP-sensitive manner. The potency...
We have characterized the in vitro binding of a new ligand, [125I]epidepride, and used this substituted benzamide to assess sensitivity dopamine D-2 receptors sodium. Both direct indirect studies with [125I]epidepride unlabeled epidepride, respectively, demonstrated that affinity for ligand was decreased from 20 30 pM presence sodium 350 500 absence The density sites identical NaCl. time courses association dissociation were not consistent simple bimolecular reactions, suggesting possibility...
Although several antidepressants (including fluoxetine, imipramine, citalopram, venlafaxine, and duloxetine) are known to inhibit the serotonin transporter (SERT), whether or not these molecules compete with 5-hydroxytryptamine (serotonin) (5-HT) for binding SERT has remained controversial. We have performed radioligand competition experiments found that all data can be fitted via a simple competitive interaction model, using Cheng-Prusoff analysis (<i>Biochem Pharmacol</i> 22:3099–3108,...
// Xiaofan Li 1 , Cristina Abrahams Abigail Yu Millicent Embry Robert Henningsen Venita DeAlmeida Shannon Matheny 2 Toni Kline Alice Yam Ryan Stafford Trevor Hallam Mark Lupher and Arturo Molina Research Development, Sutro Biopharma, South San Francisco, CA 94080, USA Clinical Correspondence to: Li, email: xli@sutrobio.com Molina, amolina@sutrobio.com Keywords: CD74; antibody-drug conjugate; non-Hodgkin lymphoma; xenograft models; STRO-001 Received: October 04, 2022 Accepted: 27, Published:...
The heptadecapeptide orphanin FQ (OFQ) has been identified as the endogenous ligand for a G protein-coupled receptor (OFQ-R), which, despite its high degree of sequence similarity to opioid receptors, fails bind ligands. We developed two radioligands OFQ-R: tritiated native OFQ peptide ([<sup>3</sup>H]OFQ) and radioiodinated form in which Leu14 was substituted by tyrosine (<sup>125</sup>I-Tyr14-OFQ). Their binding properties were examined human embryonic kidney (HEK) 293 Chinese hamster...
Several serotonin reuptake inhibitors are in clinical use for treatment of depression and anxiety disorders. However, to date, reported pharmacological differentiation these ligands has focused mainly on their equilibrium binding affinities the transporter. This study takes a new look at antidepressant modes using radioligand assays with [<sup>3</sup>H]<i>S</i>-citalopram determine kinetic rate constants across multiple temperatures. The observed dissociation 26°C fall into narrow range all...
Abstract Folate receptor alpha (FolRα) is a glycosylphosphatidylinositol linked cell-surface glycoprotein that widely expressed in serous and epithelial ovarian cancer, endometrial adenocarcinoma, non-small cell lung cancer triple negative breast cancer. In contrast, FolRα expression highly restricted on normal tissues, making it promising target for therapy using antibody drug conjugates (ADCs). We have designed novel, FolRα-targeting ADC, STRO-002, with potent cytotoxic activity expressing...
Multiple genetic polymorphisms of the human dopamine D4 receptor (hD4R) have been identified including a 12 bp repeat in exon 1 associated with psychotic condition called delusional disorder. Competition binding assays revealed minor pharmacological differences between recombinant A1 (normal) and A2 (delusional) proteins respect to quinpirole antipsychotic clozapine, however no functional were detected for activation by dopamine, epinephrine, or norepinephrine. Our results suggest that this...
Abstract OBJECTIVES: Folate receptor alpha (FolRα) is a cell-surface glycoprotein, highly expressed in ovarian and endometrial adenocarcinoma, thus promising target for cancer therapy using antibody drug conjugates (ADCs). Most ADCs currently development are generated by random attachment of the cytotoxic payload to result heterogeneous mixture, comprised many different forms that likely vary stability activity, therefore may be suboptimal therapeutic agents. We have employed an E. coli...