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January 2022 "Voltaire argued, “Perfection is attained by slow degrees; it requires the hand of time.” However, in drug discovery projects, perfection can’t be attained soon enough. A project to develop a perfect drug, or a drug that is as safe and effective as possible, may never begin if it can’t be completed quickly. Such predicaments must have been familiar to the philosopher. After all, he also complained that the perfect is the enemy of the good. If only Voltaire were here today to see how drug discovery is being accelerated by new technologies. He might reverse himself and declare that the perfect can in fact be the friend of the good. Several new technologies that are being used to accelerate drug discovery are highlighted in this article. They include small molecules that conditionally modulate proteins in their functional state; three-dimensional (3D) cell models, or organoid models, that assist with target identification, high-throughput drug screening, drug efficacy analyses, and toxicity studies; technologies that stabilize G protein–coupled receptors (GPCRs) to enable the discovery of agonistic biologics; and automated instrumentation that enables the overnight synthesis of mRNA." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "The atypical chemokine receptor 1 (ACKR1) was discovered on erythrocytes as the Duffy blood group antigen ( Cutbush et al., 1950 ), also called Duffy-antigen/receptor for chemokines, or DARC ( Novitzky-Basso and Rot, 2012 ). Erythrocytes are terminally differentiated anuclear cells with no transcription and limited translation. Accordingly, within the erythroid lineage ACKR1 expression occurs first and is the highest in erythroblasts ( Duchene et al., 2017 ). Additionally, ACKR1 expression characterizes venular endothelial cells (ECs) ( Pruenster et al., 2009 ; Thiriot et al., 2017 ), including those lining bone marrow (BM) sinusoids ( Duchene et al., 2017 ). This well-established, distinctive pattern of cell expression has been directly challenged by a publication purporting ACKR1 expression in mouse BM by macrophages, but not erythroblasts and ECs, suggesting that macrophage ACKR1 engages its non-cognate ligand CD82 on hematopoietic stem cells (HSCs) to maintain their quiescence ( Hur et al., 2016 ). In light of the extensive literature, these findings have been particularly provocative, as this was the first description of ACKR1 expression by any leukocyte type and, if correct, would change current concepts of ACKR1 involvement in pathophysiology. The reported ACKR1 expression by macrophages in Hur et al. relied on using commercial anti-ACKR1 antibody FAB6695, which has neither been validated by the manufacturer nor by the authors. This prompted us to investigate the specificity of FAB6695 and scrutinize the apparent ACKR1 expression in BM macrophages" Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "GPCRs in Medicinal Chemistry Event 8th RSC / SCI symposium on GPCRs in Medicinal Chemistry Dates Wednesday-Friday, 5th-7th October 2022 Place Evotec Campus Levi-Montalcini, Verona, Italy Downloads and Links Registration closing dates: 6th September – registration against invoice (bank transfers): Tuesday, 6th September 30th September – online registration (card payments)" Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 Structure Therapeutics Extends Financing, Advances Diabetes and Obesity Clinical Program and Changes Name from ShouTi "San Francisco and Shanghai – August 1, 2022 – Structure Therapeutics Inc. (Structure Therapeutics), formerly known as ShouTi Inc., today announced it closed an oversubscribed $33 million financing round, extending its $100 million Series B financing, which was announced in October 2021. In addition, Structure Therapeutics has completed dosing in a single ascending dose (SAD) Phase 1 study of its lead type 2 diabetes and obesity program, GSBR-1290." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonary fibrosis are currently ongoing using ligands with differing levels of selectivity and affinity as GPR84 antagonists. Although blockade of GPR84 may potentially prove effective also in diseases associated with inflammation of the lower gut there is emerging interest in defining if agonists of GPR84 might find utility in conditions in which regulation of metabolism or energy sensing is compromised. Here, we consider the physiological and pathological expression profile of GPR84 and, in the absence of direct structural information, recent developments and use of GPR84 pharmacological tool compounds to study its broader role and biology. " Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "August 12, 2022.- Jan Steyaert, scientific director of the VIB-VUB Center for Structural Biology, Vlaams Instituut Biotechnologie, at the Vrije Universiteit Brusle, Brussels, Belgium, has been named the winner of Brandeis’ 24th Jacob and Louise Gabbay Award in Biotechnology and Medicine. Jan Steyaert will be presented with the Gabbay Award at Brandeis University on October 27 when he will give a public lecture on his work, followed by a ceremony. This award recognizes the combination of Steyaert’s fundamental research and his ability to apply the research to the development of therapeutic technologies. Steyaert bridged fundamental high-impact research in biomedical sciences with the mechanistic understanding of one of the biggest classes of pharmaceutical targets by combining structural biology and advanced biotechnology." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "THOUSAND OAKS, Calif. and SAN CARLOS, Calif., Aug. 4, 2022 /PRNewswire/ -- Amgen (NASDAQ: AMGN) and ChemoCentryx, Inc., (NASDAQ: CCXI), a biopharmaceutical company focused on orally administered therapeutics to treat autoimmune diseases, inflammatory disorders and cancer, today announced that the companies have entered into a definitive agreement under which Amgen will acquire ChemoCentryx for $52 per share in cash, representing an enterprise value of approximately $3.7 billion." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 Addex and Indivior Extend GABAB Positive Allosteric Modulator Research Collaboration for Substance Use Disorders "Geneva, Switzerland, August 15, 2022 - Addex Therapeutics (SIX and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, today announced that its collaboration agreement with Indivior PLC (LON: INDV) for discovering and developing novel oral gamma-aminobutyric acid subtype B (GABAB) positive allosteric modulator (PAM) drug candidates has been extended until March 31, 2023. As part of the amended agreement, Indivior will provide Addex with CHF 850,000 (approx. US $900,000) of additional research funding. The reserved indications, where Addex retains exclusive rights to develop its own independent GABAB PAM program, have also been expanded to include chronic cough, in addition to the rights to develop certain retained compounds for Charcot-Marie-Tooth type 1A neuropathy (CMT1A) and pain. " Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Geneva, Switzerland, August 18, 2022 - Addex Therapeutics (SIX and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, today reported its half-year and second quarter financial results for the periods ended June 30, 2022 and provided a corporate update. “The recent financing from Armistice Capital and the extension of our strategic collaboration with Indivior have set us on a solid path to execute on our strategic priorities, including pursuing additional collaborations across our portfolio,” said Tim Dyer, CEO of Addex. “In addition, we are looking forward to the data read-out from the ADX71149 epilepsy Phase 2 study in Q1 2023 and continue to evaluate the path forward for dipraglurant in a number of interesting disease areas in parallel to discussions with potential strategic partners.”" Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "August 10, 2022 Cancer Research UK is working with global biopharma Sosei Heptares on a treatment they hope will bring immunotherapy benefits to new cancer types. Jonah Comstock delves into what makes this team-up tick. Cancer Research UK, a charity dedicated to funding lifesaving oncology research, spent £388 million on cancer research last fiscal year. Much of that funding is distributed to support third party research, but the group also does its own research into promising therapy areas, working with partners who have a good idea but don’t have all the necessary tools to drive it forward." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 Karuna Therapeutics Announces Positive Results from Phase 3 EMERGENT-2 Trial of KarXT in Schizophrenia "BOSTON--(BUSINESS WIRE)--Aug. 8, 2022-- Karuna Therapeutics, Inc. (NASDAQ: KRTX), a clinical-stage biopharmaceutical company driven to create and deliver transformative medicines for people living with psychiatric and neurological conditions, today announced positive topline results from its Phase 3 EMERGENT-2 trial evaluating the efficacy, safety, and tolerability of its lead investigational therapy, KarXT (xanomeline-trospium), in adults with schizophrenia. The trial met its primary endpoint, with KarXT demonstrating a statistically significant and clinically meaningful 9.6-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo (-21.2 KarXT vs. -11.6 placebo, p<0.0001) at Week 5 (Cohen’s d effect size of 0.61). KarXT also demonstrated an early and sustained statistically significant reduction of symptoms, as assessed by PANSS total score, starting at Week 2 and maintained such reduction through all timepoints in the trial." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "WELCOME 4GPCRnet meeting bringing together four of the biggest GPCR networks in Europe for a joint meeting in Leipzig. Four of the biggest European networks on GPCR research (COST Actions Adher’n Rise and ERNEST plus DFG-funded SFB1423 and FOR2372) have joined forces to organize an international meeting, which will take place from 26th-29th September 2022 in the beautiful city of Leipzig in Germany. We aim to connect renowned international experts of the field with early career ‘rising stars’. The event will take place in the heart of Leipzig, which offers a colorful mixture of culture and vivid social life." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Join Us in Boston for Discovery On Target 2022! Discovery on Target (DOT) highlights advances in current and emerging “hot” targets and technologies, as well as target validation strategies for the discovery and development of novel therapeutic agents ranging from biologics to small molecules." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Abstract The β3 -adrenergic receptor (β3 -AR) is found in several tissues such as adipose tissue and urinary bladder. It is a therapeutic target because it plays a role in thermogenesis, lipolysis, and bladder relaxation. Two β3 -AR agonists are used clinically: mirabegron 1 and vibegron 2, which are indicated for overactive bladder syndrome. However, these drugs show adverse effects, including increased blood pressure in mirabegron patients. Hence, new β3 -AR agonists are needed as starting points for drug development. Previous pharmacophore modeling studies of the β3 -AR did not involve experimental in vitro validation. Therefore, this study aimed to conduct prospective virtual screening and confirm the biological activity of virtual hits. Ligand-based pharmacophore modeling was performed since no 3D structure of human β3 -AR is yet available. A dataset consisting of β3 -AR agonists was prepared to build and validate the pharmacophore models. The best model was employed for prospective virtual screening, followed by physicochemical property filtering and a docking evaluation. To confirm the activity of the virtual hits, an in vitro assay was conducted, measuring cAMP levels at the cloned β3 -AR. Out of 35 tested compounds, 4 compounds were active in CHO-K1 cells expressing the human β3 -AR, and 8 compounds were active in CHO-K1 cells expressing the mouse β3 -AR." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 RAB-Symposium - Regulatory Autoantibodies Targeting GPCRs. September 15-16, 2022. Lübeck, Germany. Hybrid meeting. "Dear Sir or Madam, dear Colleagues, It gives me great pleasure to announce the fourth hybrid symposium on regulatory autoantibodies targeting G-protein-coupled receptors (GPCRs) in Lübeck. GPCRs are involved in a variety of physiological and pathophysiological processes. So far, numerous therapeutics targeting GPCRs have been developed, with a focus on small molecules and monoclonal antibodies for the treatment of cancer, infections, metabolic disorders or inflammatory diseases. Recently, functional autoantibodies targeting GPCRs have been associated with various disease-specific manifestations, highlighting a potential new area for therapeutic intervention. Therefore, the aim of this symposium is to bring together the current knowledge on the role of autoantibodies targeting GPCRs in various diseases, such as cardiovascular diseases, renal diseases, autoimmune diseases such as systemic sclerosis or systemic lupus erythematosus. In addition, one aim is to bring together the mode of action of autoantibodies in immune regulation and pathogenesis." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "We are proud to announce that SYnAbs is now officially accredited as a Research Tax Credit by the French Ministry of Higher Education and Research for 2022-2023-2024. I would like to take this opportunity to thank all our French partners who trust us in the generation of their monoclonal antibodies against small molecules and transmembrane receptors! #technology #lifescience #immunology #antibodies #medicine #cancer #innovation #gpcr #synabs #monoclonalantibodies #drugdiscovery #biotechnology #research #ionchannels #biologics #biotech #pharma #pharmaindustry #pharmaceuticals #oncology #healthcare #drugdevelopment" Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "CHESTERBROOK, Pa., Aug. 11, 2022 (GLOBE NEWSWIRE) -- Trevena, Inc. (Nasdaq:TRVN), a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with central nervous system (CNS) disorders, today reported its financial results for the second quarter ended June 30, 2022 and provided an overview of its recent operational highlights." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "We are happy to announce you our 2nd IRN i-GPCRnet meeting that will be held at the University of Wurzburg (Germany) from september 30th to october 1rst." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Abstract Chemokines such as stromal derived factor 1 and their G protein coupled receptors are well-known regulators of the development and functions of numerous tissues. C-X-C motif chemokine ligand 12 (CXCL12) has two receptors: C-X-C chemokine motif receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3). ACKR3 has been described as an atypical "biased" receptor because it does not appear to signal through G proteins and, instead, signals solely through the β-arrestin pathway. In support of this conclusion, we have shown that ACKR3 is unable to signal through any of the known mammalian G α isoforms and have generated a comprehensive map of the G α activation by CXCL12/CXCR4. We also synthesized a series of small molecule ligands which acted as selective agonists for ACKR3 as assessed by their ability to recruit β-arrestin to the receptor. Using select point mutations, we studied the molecular characteristics that determine the ability of small molecules to activate ACKR3 receptors, revealing a key role for the deeper binding pocket composed of residues in the transmembrane domains of ACKR3. The development of more selective ACKR3 ligands should allow us to better appreciate the unique roles of ACKR3 in the CXCL12/CXCR4/ACKR3-signaling axis and better understand the structural determinants for ACKR3 activation. SIGNIFICANCE STATEMENT: We are interested in the signaling produced by the G protein coupled receptor atypical chemokine receptor 3 (ACKR3), which signals atypically. In this study, novel selective ligands for ACKR3 were discovered and the site of interactions between these small molecules and ACKR3 was defined. This work will help to better understand the unique signaling roles of ACKR3." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 A new Kunitz-type snake toxin family associated with an original mode of interaction with the vasopressin 2 receptor "Abstract Background and purpose: Venomous animals express numerous Kunitz-type peptides. The mambaquaretin-1 (MQ1) peptide identified from the Dendroaspis angusticeps venom is the most selective antagonist of the arginine-vasopressin V2 receptor (V2R) and the only unique Kunitz-type peptide active on a GPCR. We aimed to exploit other mamba venoms to enlarge the V2R-Kunitz peptide family and gain insight into the MQ1 molecular mode of action. Experimental approach: We used a bio-guided screening assay to identify novel MQs and placed them phylogenetically. MQs were produced by solid-phase peptide synthesis and characterized in vitro by binding and functional tests and in vivo by diuresis measurement in rats. Key results: Eight additional MQs were identified with nanomolar affinities for the V2R, all antagonists. MQs form a new subgroup in the Kunitz family, close to the V2R non-active dendrotoxins and to two V2R-active cobra toxins. Sequence comparison between active and non-active V2R Kunitz peptides highlighted five positions, among which four are involved in V2R interaction and belong to the two large MQ1 loops. We finally determined that eight positions, part of these two loops, interact with the V2R. The variant MQ1-K39A showed a higher affinity for the hV2R, but not for the rat V2R. Conclusions and implications: A new function and mode of action is associated with the Kunitz peptides. The number of MQ1 residues involved in V2R binding is large and may explain its absolute selectivity. MQ1-K39A represents the first step in the improvement of the MQ1 design from a medicinal perspective." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Abstract Sigma receptor is a transmembrane non-GPCR protein expressed mainly in the endoplasmic reticulum membrane associated with mitochondria. It is classified into two types: Sigma-1 (S1R) and Sigma-2 (S2R) based on their biological functions. S1R has been implicated in many neurological disorders such as anxiety, schizophrenia, and depression. Therefore, S1R ligands possess a variety of potential clinical applications with a great interest in the treatment of neuropathic pain. In this study, we report the discovery of a novel lead compound for S1R binding, based on the thiazolidine-2,4-dione nucleus. We have explored hydrophobic groups of different sizes on both sides of the five-membered ring scaffold guided by the crystal structure of S1R. Six compounds showed more than 50% displacement of the radioligand at 10 µM concentration with compound 6c resulting in 100% displacement and a Ki of 95.5 nM. Moreover, compounds 6c and 6e showed a significant selectivity over S2R. In addition, molecular docking predicted that all the compounds showed the critical salt bridge with Glu172 with variable degrees of π-stacking interaction with Tyr103. Upon optimization, this series of compounds could represent potential clinically useful S1R ligands for pain management." Read more at the source #DrGPCR #GPCR #IndustryNews

August 2022 "Abstract Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands and analogues for their pharmacologic activities and potential therapeutic utility toward diseases of bone and mineral ion metabolism. Divergence, however, in the amino acid sequences of rodent and human PTH receptors (rat and mouse PTH1Rs are 91% identical to the human PTH1R) can lead to differences in receptor-binding and signaling potencies for such ligands when assessed on rodent vs human PTH1Rs, as shown by cell-based assays in vitro. This introduces an element of uncertainty in the accuracy of rodent models for performing such preclinical evaluations. To overcome this potential uncertainty, we used a homologous recombination-based knockin (KI) approach to generate a mouse (in-host strain C57Bl/6N) in which complementary DNA encoding the human PTH1R replaces a segment (exon 4) of the murine PTH1R gene so that the human and not the mouse PTH1R protein is expressed. Expression is directed by the endogenous mouse promoter and hence occurs in all biologically relevant cells and tissues and at appropriate levels. The resulting homozygous hPTH1R-KI (humanized) mice were healthy over at least 10 generations and showed functional responses to injected PTH analog peptides that are consistent with a fully functional human PTH1R in target bone and kidney cells. The initial evaluation of these mice and their potential utility for predicting behavior of PTH analogues in humans is reported here." Read more at the source #DrGPCR #GPCR #IndustryNews

July 2022 "G.CLIPS biotech is 2 years old today🎂. When I came this morning to work this is how I found my desk. So very grateful to the great hard working team we have and all the great achievements we have done together. Looking forward for more 🎊 #team #grateful #biotech #work #birthdaycelebration" Read more at the source #DrGPCR #GPCR #IndustryNews

July 2022 "Today we are celebrating ten years of Exscientia! Founded as a spinout from the University of Dundee on 20 July 2012, Exscientia pioneered the design of novel compounds through artificial intelligence. We have achieved a great deal in the last decade, such as the first-ever AI-designed drug candidates to enter clinical trials, the first AI-driven precision medicine platform clinically validated to guide treatment selection in patients with advanced haematological cancers, international partnerships with pharma and healthcare foundations, and the establishment of a global company with locations in the UK, U.S., Austria, and Japan which IPO’d in October last year. We’re excited about delivering the next ten years of Exscientia and advancing AI to design better drugs, faster. #artificialintelligence #drugdesign #drugdiscovery" Read more at the source #DrGPCR #GPCR #IndustryNews

July 2022 "Not even a PIPE financing could save X4 Pharmaceuticals from enacting layoffs and trimming its pipeline. The Boston biotech revealed Wednesday afternoon that it would downsize its research to focus on its lead program, mavorixafor, and lay off about 20% of its staff. The move comes less than three weeks after X4 pulled together a $55 million PIPE and amended a loan facility with Hercules Capital to reduce cash burn." Read more at the source #DrGPCR #GPCR #IndustryNews

July 2022 "I’m happy to share that I’m starting a new position as Scientific co-founder LASEREDD Therapeutics" Ross Bathgate Read more at the source #DrGPCR #GPCR #IndustryNews

July 2022 Confo Therapeutics receives €1.7 million VLAIO grant for further research on GPCR modulators for rare diseases "29/06/2022 Confo Therapeutics, founded in 2015 as a spin-off from VIB and VUB, announced today that it has been awarded a €1.7 million grant from the Flemish Agency for Innovation and Entrepreneurship (VLAIO). The grant should help expand Confo Therapeutic’s research on G protein-coupled receptor (GPCR) drug candidates. " Read more at the source #DrGPCR #GPCR #IndustryNews

"We recently hosted our annual Scientific Advisory Board (SAB) summit at our site within Granta Park. It was great to bring everyone together and also welcome new member John Parkinson." Read more at the source #DrGPCR #GPCR #IndustryNews

July 2022 "July 19, 2022 07:00 AM Eastern Daylight Time BOSTON--Tectonic Therapeutic, Inc. a pre-clinical stage biotechnology company transforming the discovery of novel GPCR-targeted therapies (G-Protein Coupled Receptors), today announced the promotion of Senior Vice President, Head of Research, Peter McNamara, PhD, to Chief Scientific Officer as well as the appointments of Barry Rubenstein as Senior Vice President, People and Culture and Washington Alves as Vice President, Biologics Manufacturing." Read more at the source #DrGPCR #GPCR #IndustryNews

July 2022 "Ad Hoc Announcement Pursuant to Art. 53 LR Geneva, Switzerland, July 22, 2022 – Addex Therapeutics Ltd (SIX: ADXN and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, today announced that it has entered into a definitive agreement with Armistice Master Fund LTV, a healthcare-focused institutional investor, to sell 3,300,000 shares in the form of 550,000 American Depositary Shares (“ADSs”) at a gross purchase price of $1.70 per ADS, which is equivalent to CHF 0.27 per share. Each ADS represents six shares. Additionally, Addex has agreed to issue to Armistice Capital unregistered pre-funded warrants to purchase up to 11,700,000 shares in the form of 1,950,000 ADSs (the “Unregistered Pre-Funded Warrants”) at a funded amount of $1.69 with $0.01 payable on exercise as well as unregistered warrants to purchase up to 15,000,000 shares in the form of 2,500,000 ADSs (the “Unregistered Warrants” and together with the “Unregistered Pre-Funded Warrants”, the “Warrants”) in a concurrent private placement. The Unregistered Warrants have an exercise price of $1.90 per ADS, will become exercisable in 60 days after their date of issuance and will expire five years from their date of issuance. " Read more at the source #DrGPCR #GPCR #IndustryNews