title: N-(2-Hydroxypropyl)methacrylamide Copolymer-Drug Conjugates for Combination Chemotherapy of Acute Myeloid Leukemia.
abstract: There is a need for new treatment strategies of acute myeloid leukemia (AML). In this study, four different drugs, including cytarabine, daunorubicin, GDC-0980, and JS-K, were investigated in vitro for the two-drug combinations treatment of AML. The results revealed that cytarabine and GDC-0980 had the strongest synergism. In addition, cell cycle analysis was conducted to investigate the effect of the different combinations on cell division. For future in vivo application, N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-cytarabine and GDC-0980 conjugates were synthesized, respectively. In vitro studies demonstrated that both conjugates had potent cytotoxicity and their combination also showed strong synergy, suggesting a potential chemotherapeutic strategy for future AML treatment.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah 84112, USA.|Division of Hematology and Hematologic Malignancies and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Shami
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah 84112, USA. Jindrich.Kopecek@utah.edu.|Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA. Jindrich.Kopecek@utah.edu.
authors.forename: Jindřich
authors.initials: J
authors.lastname: Kopeček
mesh_terms: D000178:Acrylamides; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: C569670:1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno(3,2-d)pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one; D000178:Acrylamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004337:Drug Carriers; D011743:Pyrimidines; D003561:Cytarabine; C032976:N-(2-hydroxypropyl)methacrylamide; D003630:Daunorubicin
keywords: N-(2-hydroxypropyl)methacrylamide; acute myeloid leukemia; combination chemotherapy