Dr. Omprakash Tanwar’s Post

This case study details how Prolytix developed and validated a novel plasma fractionation technology to precipitate immunoglobulins (IgG) from human blood plasma that effectively removes procoagulant contaminants. The novel method offers notable improvements over the conventional Cohn process to precipitate IgG—it takes considerably less time (48-72 hours vs. 7-10 days) and produces a significantly higher yield of IgG (>80% vs. 50-60%).   The case study includes discussion of: + The risks of procoagulant contaminants in plasma-derived biotherapeutics + The limitations of the Cohn process in producing IgG + The methods Prolytix used to create a scalable process for IgG production + The approach Prolytix used to analyze and remove procoagulant contaminants while developing the novel process   Read it now: https://lnkd.in/e3yV52zy John Moriarity #ProcessDevelopmentServices #BioanalyticalServices #BioanalyticalCRO #BioanalyticalTesting

TU7710, a long-acting recombinant activated factor VIIa developed by TiumBio to treat #hemophilia, showed an extended half-life compared with the recombinant human coagulation factor VIIa NovoSeven® RT, a conventional hemophilia treatment. https://brnw.ch/21wLr96

Ciprofloxacin (CPX) is one of the most employed antibiotics in clinics to date. However, the rise of drug-resistant bacteria is dramatically impairing its efficacy, especially against life-threatening pathogens, such as Pseudomonas aeruginosa. This Gram-negative bacterium is an opportunistic pathogen, often infecting immuno-compromised patients with severe or fatal outcomes. The evidence of the possibility of exploiting Carbonic Anhydrase (CA, EC: 4.2.1.1) enzymes as pharmacological targets along with their role in P. aeruginosa virulence inspired the derivatization of CPX with peculiar CA-inhibiting chemotypes. Thus, a large library of CPX derivatives was synthesized and tested on a panel of bacterial CAs and human isoenzymes I and II. Selected derivatives were evaluated for antibacterial activity, revealing bactericidal and antibiofilm properties for some compounds. Importantly, promising preliminary absorption, distribution, metabolism, and excretion (ADME) properties in vitro were found and no cytotoxicity was detected for some representative compounds when tested in Galleria mellonella larvae.

New: Sensitive MS-assay for detection of polysorbate-degrading HCPs in mAb products. Polysorbate surfactants are crucial to the stability and efficacy of monoclonal antibody (mAb) products, and polysorbate degradants may form particles which pose a risk to patient safety. Consequently, polysorbate stability is a major concern in mAb development and may cause delays, often in the late stages of project development. For this reason, we have collaborated with our clients to develop a highly sensitive mass spectrometry (MS)-based assay for detecting polysorbate-degrading host cell proteins (HCPs) in mAb products. 🖼 For more information, download our newest poster on the MS assay by Victor Chrone, Vasileios Tsiamis, Cecilie Hovitz Lautrup-Larsen, Ejvind Mørtz, and Thomas Kofoed – presented by Thomas at the 2024 BEBPA HCP Conference.

#Serrawettin #W2_FL10 (derived from #Serratia_marcescens), has potential antibiotic activity against #Staphylococcus_aureus. NOTES: - W2-FL10 exhibited potent activity against the Gram-positive bacteria S. aureus, #Enterococcus_faecalis, #Enterococcus_faecium, #Listeria_monocytogenes, and #Bacillus_subtilis, with minimum inhibitory concentration (MIC) values ranging from 6.3 to 31.3 μg/mL - No activity was observed against #Gram_negative bacteria. - W2-FL10 interacted with key cell membrane components, such as lipid phosphatidyl glycerol and #lipoteichoic_acid of S. aureus. - Upon membrane interaction, W2-FL10 dissipated membrane potential within 12 min and increased S. aureus membrane permeability within 28–40 min, albeit at slower rates and higher concentrations than the lytic peptide #melittin.

New Article: A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR Bitter taste receptors (TAS2Rs) are a subfamily of G-protein coupled receptors (GPCRs). Here, the authors report a cryo-EM structure of the human TAS2R14 in complex with its signaling partner gustducin, and bound to an anti-inflammatory drug flufenamic acid (FFA). https://lnkd.in/gYY2GuGw

Natural polyphenols inhibited all types of S-RBD binding with ACE-2. We do not need special chemical compounds to protect against infections by coronaviruses. We have to take care of our daily lifestyle. Now, how to inhibit the multiplication of enzymes. Natural polyphenols as inhibitors for the binding of COVID-19 S-RBD with ACE-2, T. Hanai, Journal of Human Health Research - 2(1):9-16.DOI: 10.14302/issn.2576-9383.jhhr-24- 4960 Abstract The binding strength of Covid-19 variants, Omicron BQ.1, XBB.1.5, XBB 1.16, FE.1, EG.5, BA.2.86, HV.1, and JN.1, with the ACE-2, was calculated in silico and evaluated with previous variants; the binding strength of new variants is XBB.1.5 << BA.2.86 < Delta < JN.1 < HV.1 < BA.1 << BA.2. The binding strength of Omicron JN.1 was similar to that of Delta, and that of others was less than that of BA.2.86. The binding inhibition of natural polyphenols was analyzed using a popular Omicron JN.1. The natural polyphenols were (-) Catechin, (+) Catechin, (+) epicatechin, apigenin, apigetrin, daidzein, quercetin, genistein, and oleuropein. The ionization of phenolic hydroxy groups was defined based on the atomic partial charge of oxygen. Polyphenols’ ionized hydroxy groups inhibited the binding of JN.1 S-RPB with ACE-2

From their abstract: Despite their clinical relevance in drug disposition and pharmacokinetics, the structure and mechanism of OATPs are unknown. Here we present cryo-EM structures of human OATP1B1 and OATP1B3 bound to synthetic Fab fragments and in functionally distinct states. A single estrone-3-sulfate molecule is bound in a pocket located in the C-terminal half of OATP1B1. The shape and chemical nature of the pocket rationalize the preference for diverse organic anions and allow in silico docking of statins. The structure of OATP1B3 is determined in a drug-free state but reveals a bicarbonate molecule bound to the conserved signature motif and a histidine residue that is prevalent in OATPs exhibiting pH-dependent activity.

Fragment Hit-Finding Campaigns against Ubiquitin Ligases with Charles Wartchow from Novartis. An important challenge for ligase-based targeted protein degradation (TPD) is identifying new ligands for existing ligases. Because ubiquitin ligases are usually part of a multi-subunit protein that contains one or more binding partners, hit-finding assays need to differentiate binding locations. To identify new chemotypes for the VHL and cereblon ligases, we used various hit finding methods including fragment screening. I will describe our results and the complexities we encountered. https://lnkd.in/dxXKSHtp Save $150 with Discount code SPK150. #drugdiscoverychemistry

Daprodustat (JESDUVROQ): The First HIF-PHD Inhibitor Approved for Anemia in the US | https://lnkd.in/gwhaXM7M GSK's daprodustat is the first HIF-prolyl hydroxylase domain (PHD) inhibitor approved for the treatment of anemia in chronic kidney disease (CKD) on dialysis in the US. PHDs have been attractive targets for treating anemia, especially in CKD patients, because the enzymes regulate levels of hypoxia-inducible factors (HIFs) including HIF-2, which induces the production of erythropoietin that in turn stimulates red blood cell production. This article highlights why HIF-PHDs are anemia targets, how daprodustat mimics the natural co-factor 2-oxoglutarate, and how the small molecule drug has similar safety and activity as epoetin alfa, an injected biologic. Article | https://lnkd.in/gwhaXM7M