دورية أكاديمية
أعرض في EDS

Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin E Conjugate.

التفاصيل البيبلوغرافية
العنوان: Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin E Conjugate.
المؤلفون: Machulkin AE; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Uspenskaya AA; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Zyk NU; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Nimenko EA; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Ber AP; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Petrov SA; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Polshakov VI; Center for Magnetic Tomography and Spectroscopy, Faculty of Fundamental Medicine, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Shafikov RR; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation.; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, GSP-7, Ulitsa Miklukho-Maklaya, 16/10, Moscow 117997, Russian Federation., Skvortsov DA; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Plotnikova EA; National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 2 Botkinskiy Proezd, 3, Moscow 125284, Russian Federation., Pankratov AA; National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 2 Botkinskiy Proezd, 3, Moscow 125284, Russian Federation., Smirnova GB; N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye Shosse, Moscow 115478, Russian Federation., Borisova YA; N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye Shosse, Moscow 115478, Russian Federation., Pokrovsky VS; N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye Shosse, Moscow 115478, Russian Federation.; RUDN University, Miklukho-Maklaya Street 6, Moscow 117198, Russian Federation., Kolmogorov VS; National University of Science and Technology MISiS, 9 Leninskiy Prospekt, Moscow 119049, Russian Federation., Vaneev AN; National University of Science and Technology MISiS, 9 Leninskiy Prospekt, Moscow 119049, Russian Federation., Khudyakov AD; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Chepikova OE; Department of Biotechnology, Sirius University of Science and Technology, 1 Olympic Avenue, Sochi 354340, Russian Federation., Kovalev S; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Zamyatnin AA Jr; Department of Biotechnology, Sirius University of Science and Technology, 1 Olympic Avenue, Sochi 354340, Russian Federation.; Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Trubetskaya Street 8-2, Moscow 119991, Russian Federation.; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow 119992, Russian Federation.; Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, U.K., Erofeev A; National University of Science and Technology MISiS, 9 Leninskiy Prospekt, Moscow 119049, Russian Federation., Gorelkin P; National University of Science and Technology MISiS, 9 Leninskiy Prospekt, Moscow 119049, Russian Federation., Beloglazkina EK; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Zyk NV; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation., Khazanova ES; LLC Izvarino-Pharma, v. Vnukovskoe, Vnukovskoe Shosse, Fifth km., Building 1, Moscow 108817, Russian Federation., Majouga AG; Chemistry Department, Lomonosov Moscow State University, Building 1/3, GSP-1, Leninskie Gory, Moscow 119991, Russian Federation.; National University of Science and Technology MISiS, 9 Leninskiy Prospekt, Moscow 119049, Russian Federation.; Dmitry Mendeleev University of Chemical Technology of Russia, Miusskaya Square 9, Moscow 125047, Russian Federation.
المصدر: Journal of medicinal chemistry [J Med Chem] 2021 Dec 09; Vol. 64 (23), pp. 17123-17145. Date of Electronic Publication: 2021 Nov 19.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE
أسماء مطبوعة: Publication: Washington Dc : American Chemical Society
Original Publication: [Easton, Pa.] : American Chemical Society, [c1963-
مواضيع طبية MeSH: Antigens, Surface/*chemistry , Coordination Complexes/*chemistry , Coordination Complexes/*pharmacology , Glutamate Carboxypeptidase II/*chemistry , Oligopeptides/*chemistry, Cell Line, Tumor ; Coordination Complexes/chemical synthesis ; Humans ; Male ; Microsomes, Liver/enzymology ; Microsomes, Liver/metabolism ; Prostatic Neoplasms/pathology ; Reactive Oxygen Species/metabolism ; Xenograft Model Antitumor Assays
مستخلص: Prostate cancer is the second most common type of cancer among men. Its main method of treatment is chemotherapy, which has a wide range of side effects. One of the solutions to this challenge is targeted delivery to prostate cancer cells. Here we synthesized a novel small-molecule PSMA-targeted conjugate based on the monomethyl auristatin E. Its structure and conformational properties were investigated by NMR spectroscopy. Cytotoxicity, intracellular reactive oxygen species induction, and stability under liver microsomes and P450-cytochrome species were investigated for this conjugate. The conjugate demonstrated 77-85% tumor growth inhibition levels on 22Rv1 (PSMA (+)) xenografts, compared with a 37% inhibition level on PC-3 (PSMA (-)) xenografts, in a single dose of 0.3 mg/kg and a sufficiently high therapeutic index of 21. Acute, chronic, and subchronic toxicities and pharmacokinetics have shown that the synthesized conjugate is a promising potential agent for the chemotherapy of prostate cancer.
المشرفين على المادة: 0 (Antigens, Surface)
0 (Coordination Complexes)
0 (Oligopeptides)
0 (Reactive Oxygen Species)
EC 3.4.17.21 (FOLH1 protein, human)
EC 3.4.17.21 (Glutamate Carboxypeptidase II)
V7I58RC5EJ (monomethyl auristatin E)
تواريخ الأحداث: Date Created: 20211119 Date Completed: 20220121 Latest Revision: 20220121
رمز التحديث: 20221213
DOI: 10.1021/acs.jmedchem.1c01157
PMID: 34797052
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-4804
DOI:10.1021/acs.jmedchem.1c01157