In the viability assay, it was found that these compounds decreased the proliferation of peripheral blood mononuclear cells in the concentration of 10 uM.Overall,ourresults indicate that these novel compounds are potentialcheckpoint inhibitorsforcancer immunotherapy.
📌 3 Maddede Bu Makale
🎯
Amaç & Hipotez:Tumor cells benefit from some certainsignals, which are referred to as “immune checkpoints”,to escape immune-mediated destruction.
📊
Temel Bulgular & Veri:With that in mind, it is believed that the blockade of thesepoints, such as programmed cell death Ligand-1 (PD-L1) and programmed cell death 1 (PD-1), can restorean adaptative immune response against tumoral cells.In this study, we have designed and synthesized some novel peptidomimetics with a 2-aminobenzathiazole scaffold, which targetsthe PD-1/PDL-1 pathway.
💡
Sonuç & Katkı:In the viability assay, it was found that these compounds decreased the proliferation of peripheral blood mononuclear cells in the concentration of 10 uM.Overall,ourresults indicate that these novel compounds are potentialcheckpoint inhibitorsforcancer immunotherapy.
🔬Tür:Araştırma Makalesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Alan Parametreleri
Özet
Tumor cells benefit from some certainsignals, which are referred to as “immune checkpoints”,to escape immune-mediated destruction. With that in mind, it is believed that the blockade of thesepoints, such as programmed cell death Ligand-1 (PD-L1) and programmed cell death 1 (PD-1), can restorean adaptative immune response against tumoral cells.In this study, we have designed and synthesized some novel peptidomimetics with a 2-aminobenzathiazole scaffold, which targetsthe PD-1/PDL-1 pathway. In the viability assay, it was found that these compounds decreased the proliferation of peripheral blood mononuclear cells in the concentration of 10 uM.Overall,ourresults indicate that these novel compounds are potentialcheckpoint inhibitorsforcancer immunotherapy.
🔖
Bu Makaleye Atıf Yap
KÖSE, C., UYSAL, E., YAZICI, B., TUĞAY, Z., GÜLYÜZ, S., ALPTÜRK, O., YILMAZ, Ö., BİRGÜL, S. İ. D., YANIK, H., TAVUKÇUOĞLU, E., ESENDAĞLI, G., AKDEMİR, A. (2020). Design andsynthesis of novelpeptidomimetics for cancer immunotherapy. Organic Communications, Cilt: 13 - Sayı: 3, 89–102. https://ajindex.com/articles/288473
Sun, C.; Mezzadra, R.; Schumacher T.N. Regulation and function of the PD-L1 checkpoint. Immunity2018,48, 434-452. [2]Jia, L.; Zhang, Q.; Zhang, R., PD-1/PD-L1 pathway blockade works as an effective and practical therapy for cancer immunotherapy. CancerBiol.Med.2018,15,116–123. [3]Weber, J. Immune checkpoint proteins: a new therapeutic paradigm for cancer preclinical background: CTLA-4 and PD-1 blockade. Semin. Oncol.2010, 37, 430–439. [4]Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer2012, 12, 252–264. [5]Cai, S.;Yang, X.;Chen, P.;Liu, X.;Zhou, J.;Zhang, H. Design, synthesis and biological evaluation of bicyclic carboxylic acid derivatives as IDO1 inhibitors.Bioorg.Chem.2020, 94, 103356(14 pages). [6]Skalniak, L.;Zak, K.M.;Guzik, K.; Magiera, K.;Musielak, B.; Pachota, M.; Szelazek, B.; Kocik, J.;Grudnik, P.;Tomala, M.; Krzanik, S.;Pyrc, K.; Dömling, A.;Dubin, G.;Holak, T.A. Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells.Oncotarget 2017,8, 72167-72181. [7]Zarganes-Tzitzikas, T.;Konstantinidou, M.; Gao, Y.;Krzemien, D.; Zak, K.;Dubin, G.;Holak, T.A.;Dömling, A. Inhibitors of programmed cell death 1 (PD-1): a patent review (2010-2015). Expert Opin.Ther.Pat.2016,26, 973–977. [8]Bristol-Myers Squibb Company. Compounds useful as immunomodulators. WO2015/034820 A1. 2015. [9]Aurigene Discovery Technologies Limited. 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives as immunomodulators. WO2015/033301 A1. 2015. [10]Zak, K.M.; Grudnik. P.; Guzik, K.; Zieba B.J.; Musielak, B.; Dömling, A; Dubin, G.; Holak, T.A. Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1). Oncotarget2016, 7, 30323-30335. [11]Labute, P. Protonate3D: assignment of ionization states and hydrogen coordinates to macromolecular structures. Proteins2009, 75, 187–205. [12]Halgren, T.A. Merck molecular force field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions. J. Comp. Chem.1996, 17, 520-552. [13]Halgren, T.A. Merck molecular force field. III. Molecular geometries and vibrational frequencies. J. Comp. Chem.1996, 17, 553-586. [14]Halgren, T.A. Merck molecular force field. V. Extension of mmff94 using experimental data, additional computational data and empirical rules. J. Comp. Chem.1996, 17, 616-641. [15]Halgren, T.A. Merck molecular force field: I. Basis, form, scope, parameterization and performance of MMFF94. J. Comp. Ch