Belma Zengin Kurt’s Post

Highlights Dysregulated protein kinases are the driving factors for numerous malignancies. The classification and indication of small molecule kinase inhibitors are summarized. The principles of chemistry optimization for the development of kinase inhibitors are described in detail.

CADD (Computer-aided drug design) A POWERFUL TOOL FOR THE DEVELOPMENT OF KINASE INHIBITORS In biochemistry, a kinase is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule donates a phosphate group to the substrate molecule. As a result, kinase produces a phosphorylated substrate and ADP. These enzymes are involved in the regulation of various cellular processes such as growth, division, and metabolism. For this reason, kinases are a highly sought-after drug target in the pharmaceutical field. Kinase inhibitors are used to treat cancer and other diseases where abnormal kinase activity plays a key role. Designing inhibitors that are specific to one kinase requires considerable effort by medicinal chemists. CADD (Computer-aided drug design) has become a powerful tool in the development of kinase inhibitors. Not only CADD but also techniques such as molecular docking, pharmacophore modeling and virtual screening are part of the common effort in designing new kinase inhibitors. Thanks to these techniques, only in the last period - 2021-2023 - numerous kinase inhibitors have been developed and have reached FDA approval. Below are some kinase inhibitors discovered or developed with the help of CADD, and approved by FDA. #kinase #kinaseinhibitor #CADD

Carna’s kinase profiling data and Kinome Plots of 60 FDA-approved kinase inhibitors now on our website for open use! To celebrate the launch of our Mobility Shift Assay (MSA) profiling service using Sciex BioPhase™ 8800 Capillary Electrophoresis System, we have released on our website the kinase profiling data of 60 FDA-approved kinase inhibitors as performed by Carna, as well as the kinome plots that visualize the profiling results. You may download the excel data of these profiled 60 FDA-approved kinase inhibitors at https://lnkd.in/gAPm5Tkz or visit our new page at https://lnkd.in/gZ_MracS Please leverage this data for your research 😊 [Carna’s Profiling Assay Services] Carna Biosciences offers profiling assay services using only internally produced active kinase proteins. These services cover ~350 targets including mutant kinases, and ~300 wild-type kinase targets. #kinases #kinaseinhibitors #mobilityshiftassay #kinome #drugrepositioning #offtargeteffect

#FDA-approved kinase #inhibitors #discovered using the computer-aided #drug design strategy (2021–2023). #drugdesign #drugdiscovery #compchem #computationalchemistry #protacs Computer-aided drug design (CADD) has become a powerful tool in the development of kinase inhibitors, which are a class of drugs that target kinases, enzymes involved in the regulation of various cellular processes such as growth, division, and metabolism. Many of these inhibitors are used to treat cancer and other diseases where abnormal kinase activity plays a key role. Over the past few years, from 2021 to 2023, CADD has significantly contributed to the discovery and development of FDA-approved kinase inhibitors. These inhibitors are often identified through a combination of techniques like molecular docking, pharmacophore modeling, and virtual screening, which help in designing and optimizing compounds that can effectively interact with kinase targets. Here are some FDA-approved kinase inhibitors discovered or developed with the help of CADD during the period 2021–2023:

Highlights the importance of taking biophysical properties into consideration in designing novel TKIs. FGFR2 specificity vs. FGFR1. Very cool findings in PNAS.

Our prodrug technology platform enables potentially greater control over the non-hematological side effects common to kinase inhibitor therapies, such as nausea or diarrhea, and it may improve drug delivery into the target tissue. Learn more: https://bit.ly/2ZLven4

Lipid nanoparticles (LNPs) have emerged as transformative agents in chimeric antigen receptor (CAR) T cell therapy, offering significant advantages over traditional methods. They address key challenges such as immunogenicity, reduced toxicity, and improved safety. Promising preclinical results indicate a shift towards safer and more effective CAR T cell treatments. Ongoing research is focused on validating these findings in clinical trials, marking the beginning of a new era in CAR therapy. This exploration highlights the preference for LNPs due to their versatility and effective delivery of nucleic acids. Additionally, we discuss the key clinical challenges, heralding a new era in CAR T cell therapy driven by the utility of LNPs. #LipidNanoparticles #LNPs #CAR_TCellTherapy #TransformativeMedicine #Immunogenicity #ReducedToxicity #ImprovedSafety #PreclinicalResults #EffectiveTreatments #ClinicalTrials #NucleicAcidDelivery #Biocompatibility #TargetedTherapy #NextGenTherapies #Versatility #AdvancedDrugDelivery #TumorTargeting #InnovativeTherapies #CancerResearch #Biotechnology #Pharmacokinetics #Pharmacodynamics #TherapeuticNanoparticles #FutureMedicine #MedicalAdvancements #Oncology #CAR_TCellResearch #ClinicalConsiderations #MedicalInnovation #GeneTherapy #NewEraInMedicine

Unlocking the Potential of Indazole Scaffold in Kinase Inhibitors! 🔶 In the realm of medicinal chemistry, the indazole scaffold stands out as a cornerstone for the development of kinase inhibitors. This versatile heterocycle has garnered significant attention due to its remarkable ability to form pivotal interactions with hinge residues, enhancing the affinity and specificity of kinase inhibitors. 🔶 The indazole core is a substantial pharmacophore that has been fundamental in the synthesis of numerous kinase inhibitors targeting both tyrosine and serine/threonine kinases. Its presence in commercially available anticancer kinase inhibitors like axitinib, linifanib, and pazopanib underscores its clinical relevance. 🔷 Our research team recently reported the indazole derivative AKE-72 as a promising Pan-Bcr-Abl inhibitor for chronic myeloid leukemia (CML). https://lnkd.in/ezRkrK2Q ✅ As we continue to explore the therapeutic landscape, the indazole scaffold remains a beacon of innovation, driving forward the discovery and optimization of next-generation kinase inhibitors. Its adaptability and efficacy make it an invaluable asset in our ongoing battle against diseases. #MedicinalChemistry #KinaseInhibitors #IndazoleScaffold #DrugDiscovery #

IDRx announces $120 million series B financing to advance potential best-in-class new treatment for gastrointestinal stromal tumor (GIST). IDRX-42 is a potent, oral, highly selective KIT inhibitor targeting all major categories of activating and resistance mutations in patients with KIT-mutant GIST (including variants in exons 9, 11, 13 and 17). IDRX-42 was granted Orphan Drug designation by the FDA for the treatment of GIST. IDRX-42 is currently being evaluated in StrateGIST 1, a first-in-human Phase 1/1b study. In preclinical studies, IDRX-42 demonstrated superior antitumor activity compared to imatinib, the current first-line of therapy, in GIST human xenograft models expressing mutations in KIT exons 9 and 11. In xenograft models expressing secondary resistance mutations in KIT exon 13 or 17, IDRX-42 treatment resulted in potent and dose-dependent antitumor activity superior to the second-line standard of care agent, sunitinib. Chemenu has been working to develop more compounds for drug discovery. Here comes the building blocks we can provide: https://lnkd.in/gPJh_hem Keywords: IDRX-42; M4205; KIT inhibitor; GIST; building blocks  

Antibody Therapeutics (2023 CiteScore: 8.7), the official journal of Chinese Antibody Society published by Oxford University Press would like to share a research article entitled “Preclinical studies of BB-1701, a HER2-targeting eribulin-containing ADC with potent bystander effect and ICD activity”. The corresponding author is Yuhong Zhou from Bliss Biopharmaceutical. In comparison with HER2-targeting ADCs with DM1 and Dxd payload, eribulin-containing ADC demonstrated higher in vitro cytotoxicity in HER2-low cancer cell lines. BB-1701 also effectively suppressed tumors in models resistant to DM1 or Dxd containing ADCs. Mode of action studies showed that BB-1701 had a significant bystander effect on HER2-null cells adjacent to HER2-high cells. In addition, BB-1701 treatment induced immunogenic cell death (ICD). Repeated doses of BB-1701 in nonhuman primates showed favorable pharmacokinetics and safety profiles at the intended clinical dosage, route of administration, and schedule. Click the link for the free access of the full article: https://lnkd.in/gXz3gzBT We are also welcoming therapeutic antibody related submission through https://lnkd.in/dMJjtiD #Antibody #Therapeutics #ADC