Generics and Biosimilars Initiative (GaBI)’s Post

Did you know that #Ceftobiprole (a recently approved #antibiotics) is the active component of the prodrug ceftobiprole medocaril? #Prodrug Activation: Conversion of the prodrug ceftobiprole medocaril into the active compound ceftobiprole happens rapidly and is facilitated by non-specific plasma esterases. Since ceftobiprole medocaril is administered intravenously, active ceftobiprole has minimal (16%) binding to plasma proteins. The half-life of active ceftobiprole following multiple-dose administration is approximately 3.3 hours. #Mechanism of #Action: Ceftobiprole, the active component of ceftobiprole medocaril, demonstrates its bactericidal activity by inhibiting bacterial cell wall synthesis. This activity occurs through binding to essential penicillin-binding proteins (PBPs) and inhibiting their transpeptidase activity, which is crucial for the synthesis of the peptidoglycan layer of the bacterial cell wall. Ceftobiprole exhibits in vitro activity against both Gram-positive and Gram-negative bacteria. In Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), ceftobiprole binds to PBP2a. It also binds to PBP2b in Streptococcus pneumoniae (penicillin-intermediate), PBP2x in S. pneumoniae (penicillin-resistant), and to PBP5 in Enterococcus faecalis. For further details, you can explore more information about Ceftobiprole at [DrugBank](https://lnkd.in/dQrgumG5) and [FDA's official announcement] (https://lnkd.in/dkqeJ-E9).

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.

Ionizable lipids with tertiary amines generate aldehyde impurities through oxidation and hydrolysis; these impurities covalently bind to #mRNA, compromising their integrity and activity during storage. In this study, the authors identified piperidine-based ionizable lipids that maintained #mRNA/#LNP activity even after refrigerated storage as liquid formulations.   https://lnkd.in/ec-at8Kp

#WednesdayRead Focus on “Is it time to move from pigs to human beings? Testing recombinant human soluble domain of CD39L3 as an adjuvant to ticagrelor.”   Ticagrelor-treated pigs underwent balloon-induced MI (90 min) and received intravenously either AZD3366 before reperfusion. Infusion of AZD3366 on top of ticagrelor leads to enhanced cardioprotection compared with ticagrelor alone.Ticagrelor reduced oedema formation and infarct size at Day 3 post-MI vs. controls. A 3 mg/kg AZD3366 provided an additional 45% reduction in oedema and infarct size compared with ticagrelor and a 70% reduction https://lnkd.in/ekabVfYj #EHJ

Novel succinoylated carboxymethyl guar gum nanocarriers of glimepiride for controlling type-2 diabetes https://lnkd.in/gPa_Pa3p Non-toxic succinoylated guar gum was successfully prepared using DMAP as catalyst. #Glimepiride Non-toxic succinoylated guar gum was successfully prepared using DMAP as catalyst. Amphiphilic guar gum enhanced solubility of glimepiride by about 67-fold. #Nanocarriers exhibited spherical morphology with diameter of 430 nm. Nanocarriers demonstrated controlled release over 24 h in simulated GI fluids. Nanocarriers offered a great potential in controlling diabetes for 24 h. #innovation #technology #research

💡5 Essential Tips for Successful Hepatocyte Differentiation 🧫Are you working on hepatocyte differentiation from iPSCs? Our guide breaks down the key steps for efficient and reliable results. 🔗Read it here: https://lnkd.in/eyZmeZ-N #StemCellResearch #Hepatocytes #iPSCs 

If only there was a rapid, robust, reliable and customizable bioassay available for assessing Complement-Dependent Cytotoxicity (CDC)... Wait, there is :-) The iLite CDC Bioassay is delivered in an assay-ready format that eliminates cumbersome cell culture procedures. Read more about it in this informative White Paper. #DrugDevelopment #ImmunoTherapyResearch #QualityControl #ImmunologicalInvestigations #CDC #SvarLifeScience

#Biosimilar switching is effective and safe according to research published in BioDrugs Journal: Hillel Cohen and Wolfram Bodenmueller conclude: “We believe that the available data suggest that as a scientific matter, the practice of biosimilar-to-biosimilar switching is as safe and effective as being treated solely with either a reference biologic or a single biosimilar, or the switch from a reference biologic to its biosimilar. Any suggestions to the contrary are not supported by clinical evidence or the underlying science.” https://lnkd.in/eFQmW_qS

How do you systematically improve human islet isolation or any other cell isolation manufacturing process that uses collagenase enzymes? You begin with the simplest element you can control, the collagenase-protease enzyme mixtures used in cell isolation. https://lnkd.in/gGB2Bsey #biotechnology #celltherapy

Vascular access type for melflufen administration - Full Text... "Melflufen PVC and CVC administrations are bioequivalent based on melphalan pharmacokinetic parameters. Melflufen via PVC was well tolerated, with no infusion-related reactions or new safety signals and may represent an alternative route of administration" Pour et al (2024).