2-Thioxothiazolidin-4-one Analogs as Pan-PIM Kinase Inhibitors

被引：6
作者：
Yun, Yanghwan [1 ]
Hong, Victor Sukbong [1 ]
Jeong, Seungik [1 ]
Choo, Hyeonseong [1 ]
Kim, Shin [2 ]
Lee, Jinho [1 ]
机构：
[1] Keimyung Univ, Coll Nat Sci, Dept Chem, Daegu 42601, South Korea
[2] Keimyung Univ, Sch Med, Dept Immunol, Daegu 42601, South Korea
来源：
CHEMICAL & PHARMACEUTICAL BULLETIN | 2021年 / 69卷 / 09期
关键词：
rhodanine; inhibitor; leukemia; proviral integration site for Moloney murine leukemia virus (PIM) kinase; cancer; SELECTIVE INHIBITORS; CANCER; POTENT; DERIVATIVES; MECHANISMS; DISCOVERY; RHODANINE; SGI-1776; SCAFFOLD;
D O I：
10.1248/cpb.c21-00264
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Proviral integration site for Moloney murine leukemia virus (PIM) kinases are proto-oncogenic kinases involved in the regulation of several cellular processes. PIM kinases are promising targets for new drug development because they play a major role in many cancer-specific pathways, such as survival, apoptosis, proliferation, cell cycle regulation, and migration. Here, 2-thioxothiazolidin-4-one derivatives were synthesized and evaluated as potent pan-PIM kinase inhibitors. Optimized compounds showed single-digit nanomolar IC50 values against all three PIM kinases with high selectivity over 14 other kinases. Compound 17 inhibited the growth of Molm-16 cell lines (EC50 = 14nM) and modulated the expression of pBAD and p4EBP1 in a dose-dependent manner.
引用
收藏
页码：854 / 861
页数：8
相关论文
共 50 条
  • [21] Protein Translation Inhibition is Involved in the Activity of the Pan-PIM Kinase Inhibitor PIM447 in Combination with Pomalidomide-Dexamethasone in Multiple Myeloma
    Paino, Teresa
    Gonzalez-Mendez, Lorena
    San-Segundo, Laura
    Corchete, Luis A.
    Hernandez-Garcia, Susana
    Diaz-Tejedor, Andrea
    Algarin, Esperanza M.
    Mogollon, Pedro
    Martin-Sanchez, Montserrat
    Gutierrez, Norma C.
    Mateos, Maria-Victoria
    Garayoa, Mercedes
    Ocio, Enrique M.
    CANCERS, 2020, 12 (10) : 1 - 20
  • [22] New 3-amino-2-thioxothiazolidin-4-one-based inhibitors of acetyl- and butyryl-cholinesterase: synthesis and activity
    Kratky, Martin
    Novackova, Karolina
    Svrckova, Katarina
    Svarcova, Marketa
    Stepankova, Sarka
    FUTURE MEDICINAL CHEMISTRY, 2024, 16 (01) : 59 - 74
  • [23] Synthesis and Evaluation of 5-(3-(Pyrazin-2-yl)benzylidene)thiazolidine-2,4-dione Derivatives as Pan-Pim Kinases Inhibitors
    Lee, Jinho
    Park, Jongseong
    Hong, Victor Sukbong
    CHEMICAL & PHARMACEUTICAL BULLETIN, 2014, 62 (09) : 906 - 914
  • [24] Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc–Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice
    Jianxia Guo
    Robert A. Parise
    Erin Joseph
    Merrill J. Egorin
    John S. Lazo
    Edward V. Prochownik
    Julie L. Eiseman
    Cancer Chemotherapy and Pharmacology, 2009, 63 : 615 - 625
  • [25] Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice
    Guo, Jianxia
    Parise, Robert A.
    Joseph, Erin
    Egorin, Merrill J.
    Lazo, John S.
    Prochownik, Edward V.
    Eiseman, Julie L.
    CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2009, 63 (04) : 615 - 625
  • [26] The Novel Pan-PIM Kinase Inhibitor, PIM447, Displays Dual Antimyeloma and Bone-Protective Effects, and Potently Synergizes with Current Standards of Care
    Paino, Teresa
    Garcia-Gomez, Antonio
    Gonzalez-Mendez, Lorena
    San-Segundo, Laura
    Hernandez-Garcia, Susana
    Lopez-Iglesias, Ana-Alicia
    Algarin, Esperanza M.
    Martin-Sanchez, Montserrat
    Corbacho, David
    Ortiz-de-Solorzano, Carlos
    Corchete, Luis A.
    Gutierrez, Norma C.
    Maetos, Maria-Victoria
    Garayoa, Mercedes
    Ocio, Enrique M.
    CLINICAL CANCER RESEARCH, 2017, 23 (01) : 225 - 238
  • [27] Insights into the Interaction Mechanisms of the Proviral Integration Site of Moloney Murine Leukemia Virus (Pim) Kinases with Pan-Pim Inhibitors PIM447 and AZD1208: A Molecular Dynamics Simulation and MM/GBSA Calculation Study
    Chen, Qingqing
    Wang, Yan
    Shi, Shanshan
    Li, Kaihang
    Zhang, Ling
    Gao, Jian
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (21)
  • [28] Hit to lead evaluation of 1,2,3-triazolo[4,5-b]pyridines as PIM kinase inhibitors
    Pastor, Joaquin
    Oyarzabal, Julen
    Saluste, Gustavo
    Maria Alvarez, Rosa
    Rivero, Virginia
    Ramos, Francisco
    Cendon, Elena
    Blanco-Aparicio, Carmen
    Ajenjo, Nuria
    Cebria, Antonio
    Albarran, M. I.
    Cebrian, David
    Corrionero, Ana
    Fominaya, Jesus
    Montoya, Guillermo
    Mazzorana, Marco
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (04) : 1591 - 1597
  • [29] Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells
    Lee, Miso
    Lee, Kyung-Hun
    Min, Ahrum
    Kim, Jeongeun
    Kim, Seongyeong
    Jang, Hyemin
    Lim, Jee Min
    Kim, So Hyeon
    Ha, Dong-Hyeon
    Jeong, Won Jae
    Suh, Koung Jin
    Yang, Yae-Won
    Kim, Tae Yong
    Oh, Do-Youn
    Bang, Yung-Jue
    Im, Seock-Ah
    CANCER RESEARCH AND TREATMENT, 2019, 51 (02): : 451 - 463
  • [30] Synthesis, characterization and DFT calculations of linear and NLO properties of novel (Z)-5-benzylidene-3-N(4-methylphenyl)-2-thioxothiazolidin-4-one
    Bensafi, T.
    Hadji, D.
    Yahiaoui, A.
    Argoub, K.
    Hachemaoui, A.
    Kenane, A.
    Baroudi, B.
    Toubal, K.
    Djafri, A.
    Benkouider, A. M.
    JOURNAL OF SULFUR CHEMISTRY, 2021, 42 (06) : 645 - 663
12345