Exploration of Targeted Anti-tumor Therapy’s Post

"#Chemokine receptors (CKRs) are G protein–coupled receptors (#GPCR's) activated by small protein ligands called chemokines. One family member, the human CC chemokine receptor 8 (CCR8), is an emerging therapeutic #DrugTarget for cancer #Immunotherapy and #Autoimmune diseases. #SmallMolecules can act on CCR8 with a clear #MechanismOfAction (MoA) and desired route of administration. However, the underlying mechanism for selectivity of #SmallMolecule drugs and their way to activate downstream signaling is poorly understood!" In this fantastic open-access article published in Science Magazine Advances, researchers revealed the #CryoEM structures of human CCR8 complexed with Gi trimers in the ligand-free state or activated by nonpeptide #Agonists LMD-009 and ZK 756326: https://lnkd.in/eCZ5YJaB These findings present the characterization of the molecular interaction between a nonpeptide agonist and a chemokine receptor, aiding #DrugDevelopment of novel therapeutics targeting related diseases through a structure-based #DrugDesign (SBDD) approach! #CryoEM #DrugDiscovery #ImmunoOncology

China's new drug Aumolertinib Mesilate Tablets: The world's second EGFR-targeted therapy for lung cancer with gene mutations. #LungCancer #EGFRInhibitor #TargetedTherapy #Aumolertinib #NSCLC Aumolertinib Mesilate Tablets (Ameile) were approved for marketing in China on March 18, 2020. It is China's first third-generation EGFR-targeted therapy for lung cancer with gene mutations and the second such drug globally, following Osimertinib. On August 20, 2024, the new indication marketing application for Aumolertinib Mesilate Tablets was accepted for priority review by the China Center for Drug Evaluation (CDE). This indication is for the treatment of unresectable locally advanced non-small cell lung cancer (NSCLC) that has not progressed following platinum-based chemoradiotherapy. This is the fourth indication for which the drug has submitted a marketing application, and it is expected to be approved in the second quarter of 2025. The Phase 1 clinical trial (NCT0298110) enrolled a total of 120 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The results showed an objective response rate (ORR) of 52% (range: 42–63), with a disease control rate (DCR) as high as 92% (range: 84–96). The median progression-free survival was 11.0 months (95% CI: 9.5-not reached). To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine In China for preliminary evaluation! WhatsApp: +8613717959070 （Https://wa.me/+8613717959070） Email: [email protected] #CancerTreatment #ClinicalTrials #PharmaInnovation #Oncology #DrugApproval #Biotech #PrecisionMedicine

Rocket Pharmaceuticals announced the European Medicines Agency's (#EMA) acceptance of their Marketing Authorization Application (MAA) for the lentiviral (LV) vector-based investigational #genetherapy RP-L102. This #therapy is a potential breakthrough for treating the rare genetic condition #FanconiAnemia (FA). FA, stemming from mutations in the FANCA gene, hampers DNA repair and leads to symptoms like #BoneMarrowFailure, increased #cancer risk, and physical abnormalities. There are currently no available options to potentially prevent bone marrow failure for affected #patients. The EMA's nod is a crucial step forward in the company's mission to deliver this innovative treatment to those suffering from this condition. https://lnkd.in/dAvasMs5 #RareAnemias #RareDiseases #Anemia #RAIN

Article: Middle Eastern Plants with Potent Cytotoxic Effect Against Lung Cancer Cells According to Nazaem and EL-Enam (2024), the discoveries of locally resourced plants in the Middle East are a promising alternative to conventional cancer treatment, chemotherapy. Plants have been anciently practiced as a treatment. Unfortunately, only 25% of the available pharmaceutics are made from of plants. Plants were sourced and screened for their cytotoxic effects against lung cancer cells. The study concluded that eleven plants may be a future treatment alternative and a complementary food regimen. This discovery is great news! Resources: Nazeam, J. A., & EL-Emam, S. Z. (2024). Middle Eastern Plants with Potent Cytotoxic Effect Against Lung Cancer Cells. Journal of Medicinal Food, 27(2), 198–207. https://lnkd.in/g7PUDAVJ

Sains Malaysiana 53(2)(2024): 359-367 https://lnkd.in/gsa6tNtb A New Oxoaporphine and Liriodenine’s Anti-Neuroblastoma Potential from the Roots of Polyalthia bullata King (Sebatian Oksoaporfina Baharu dan Potensi Anti-Neuroblastoma Liriodenin daripada Akar Polyalthia bullata King) PHOEBE SUSSANA PRIMUS1 , CAROL HSIN-YI WU2 , CHAI-LIN KAO3 & YEUN-MUN CHOO1,* 1 ABSTRACT Polyalthia bullata King’s root yielded a new compound named 5-methylliridine (1) in addition to six previously identified compounds. These known compounds include liriodenine (2), 11-methoxyliriodenine (3), lysicamine (4), onychine (5), 5-hydroxy-6-methoxyonychine (6), and 8-methoxyeupolauridine (7). The structures of compounds 1-7 were determined through spectroscopic analysis. Liriodenine (2) exhibited a remarkable ability to decrease the cell viability of cancerous N2A cells to 22% within a 24 h timeframe, indicating its potential as an anti-neuroblastoma agent. Molecular docking results additionally suggested that oxoaporphines (1-4) have the potential to act as inhibitors of protein kinases. These findings highlight the therapeutic potential of P. bullata constituents in cancer treatment, particularly neuroblastoma, and contribute to understanding its medicinal properties. Keywords: Anti-neuroblastoma; oxoaporphine; protein kinase; Polyalthia bullata King; Tongkat Ali Hitam 

🩺 4 Decisions and an approval 🩺 Several key FDA decisions are on the horizon and an anticipated approval has been made. These 5 drugs are poised to impact treatment landscapes across critical therapeutic areas: BridgeBio Pharma's Acoramidis: Targeting transthyretin amyloidosis cardiomyopathy, this treatment could become an important option for managing this rare, debilitating heart disease. AstraZeneca's Dato-Dxd: This antibody-drug conjugate for lung cancer could help delay tumor growth. Vertex Pharmaceuticals' 'Vanza Triple': An innovative regimen for cystic fibrosis, designed for easier, once-daily dosing. Bristol Myers Squibb's Subcutaneous Opdivo: A new subutaneous formulation for all its current cancer indications, potentially providing a quicker, more convenient alternative to IV infusion PTCbio’s Upstaza: The U.S debut of this gene therapy for rare AADC deficiency is iminent after the FDA granted it accelerated approved on Wednesday this week. Take some time this weekend to read more here: https://lnkd.in/eRXDxp6n #FDA #Biotech #DrugDevelopment

Clinical Trials Market to Grow $73.2 Billion by 2028 Download Sample PDF Report-https://lnkd.in/dTiYUy2a The global clinical trials market in terms of revenue was estimated to be worth $48.2 billion in 2023 and is poised to reach $73.2 billion by 2028, growing at a CAGR of 8.7% from 2023 to 2028. Companies Working in the Market Food and Drugs Authority,Ghana      Novocure   Lambda Therapeutic Research  France Biotech Exscientia Fondazione Telethon      Cell and Gene Therapy Catapult      Eurofins Advinus MERCLINCO Vall d’Hebron Institute of Research (VHIR) - Vall d'Hebron Institut de Recerca المعهد الوطني لأبحاث الصحة | Saudi NIH     Centre for Infectious Disease Research in Zambia - CIDRZ    Drugs for Neglected Diseases initiative - DNDi PathCare ERGOMED Huma  Optos CTC Clinical Trial Consultants AB      Unicancer Zymeworks Inc.    Sovereign Pharmaceuticals Laboratorio Rapela     atai Life Sciences UNC Lineberger Comprehensive Cancer Center AlgaeCal Inc. Novartis, Australia & New Zealand      Pharma Medica Research Inc.   CellCarta Keyrus Life Science      Alimentiv University of Maryland Faculty Physicians      IDEXX BioAnalytics ParadigmIT Innovent Biologics   Innoplexus - a Partex Company    Laboratorio Hidalgo     Chesapeake Urology Associates    Derma Sciences The START Center for Cancer Care Meditrial

This essay offers an excellent collection of resources on how PROTAC (PROteolysis Targeting Chimeras) technology is pushing the boundaries of targeted therapies. By enabling the selective degradation of disease-causing proteins, PROTACs open up new possibilities for tackling traditionally "undruggable" targets. From cancer to neurodegenerative diseases, PROTACs are shaping up to be one of the most promising paths in modern medicine, with the potential to overcome resistance mechanisms and bring us closer to more effective, durable treatments. If you're curious about current trends and future developments in PROTACs, this collection is worth a look! https://lnkd.in/dPphxGG6

Development of a small molecule covalent inhibitor of the Plasmodium falciparum kinase PfCLK3 The authors solve the structure of Plasmodium falciparum cyclin-dependent kinase 3 in complex with previously-identified TCMDC-135051 bound in the ATP site, which revealed two nearby cysteine residues. The least well-conserved cysteine residue was chosen as the target for covalent inhibitor design. Three different electrophilic warheads were assessed, which were produced alongside the non-covalent control compound - only one of the three compounds showed covalent reactivity at physiological pH using MS. In a kinase assay, the covalent compound (unlike the parent compound) showed inhibition even at high (physiological) ATP levels. Interestingly, the parasite killing effect of the parental and covalent inhibitor were comparable, but the covalent compound was much more effective in washout experiments, which may more closely mimic physiology and could allow a route to a single dose malaria cure. Furthermore, this compound was shown to be more specific and less cytotoxic than the parental compound. Could the addition of covalent reactivity be a more general way to improve specificity and potency of compounds? University of Glasgow, Keltic Pharma Therapeutics, The University of Edinburgh #preprint #malaria #drugdiscovery #smallmolecule #covalent #structuralbiology #crystallography #structurebaseddrugdiscovery #massspectrometry #kinase