Preclinical in vitro and in vivo characterization of a novel, wild-type-sparing, PI3Ka H1047R mutant-selective inhibitor

被引：0
|
作者：
Smith, Aaron C.
Arwood-Levine, Ben
Born, Alexandra
Brizendine, Richard
Chatterjee, Payal
Chicarelli, Mark J.
Conner, Michael L.
Fell, Brad
Fulton, Jennifer
Guarnieri, Anna
Jalluri, Ravi
Knox, Hailey
Koch, Keith
Krischlunas, Daniel
Kumar, Vijay
McHugh, Colin
Mclean, Brent
Nassar, Kelsey
Newhouse, Brad
Rieger, Rob
Robinson, John
Rodriguez, Mareli
Salituro, Leah
Stunkard, Lee
Sullivan, Francis
Turton, Roy
Winski, Shannon
Zhou, Yeyun
机构：
来源：
CANCER RESEARCH | 2024年 / 84卷 / 09期
关键词：
D O I：
10.1158/1538-7445.SABCS23-PO3-26-01
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
PO3-26-01
引用
收藏
页数：3
相关论文
共 19 条
  • [1] Preclinical characterization of LOX-22783, a highly potent, mutant-selective and brain-penetrant allosteric PI3Kα H1047R inhibitor
    Klippel, Anke
    Wang, Rui
    Puca, Loredana
    Faber, Andrew Lee
    Shen, Weihua
    Bhagwat, Shripad V.
    Karukurichi, Kannan
    Zhang, Feiyu Fred
    Perez, Carmen
    Rama, Ramon
    Ramos, Ana
    Zheng, Yi
    Bonday, Zahid
    Thomas, James
    Brooks, Harold B.
    Kindler, Lisa J.
    Bogner, Sarah M.
    Zolfaghari, Parisa
    Hicks, Mark, II
    Callies, Sophie
    Mattioni, Brian
    LeBrun, Laurie
    Durbin, Jim
    Anderson, Erin
    Mayne, Chris
    Kesicki, Edward
    Kolakowski, Gabrielle
    Andrews, Steven W.
    Brandhuber, Barbara J.
    [J]. MOLECULAR CANCER THERAPEUTICS, 2021, 20 (12)
  • [2] In Vitro and In Vivo Characterization of Irreversible Mutant-Selective EGFR Inhibitors That Are Wild-Type Sparing
    Sjin, Robert Tjin Tham
    Lee, Kwangho
    Walter, Annette O.
    Dubrovskiy, Aleksandr
    Sheets, Michael
    St Martin, Thia
    Labenski, Matthew T.
    Zhu, Zhendong
    Tester, Richland
    Karp, Russell
    Medikonda, Aravind
    Chaturvedi, Prasoon
    Ren, Yixuan
    Haringsma, Henry
    Etter, Jeff
    Raponi, Mitch
    Simmons, Andrew D.
    Harding, Thomas C.
    Niu, Deqiang
    Nacht, Mariana
    Westlin, William F.
    Petter, Russell C.
    Allen, Andrew
    Singh, Juswinder
    [J]. MOLECULAR CANCER THERAPEUTICS, 2014, 13 (06) : 1468 - 1479
  • [3] LOXO-783: A potent, highly mutant selective and brain-penetrant allosteric PI3Kα H1047R inhibitor in combination with standard of care (SOC) treatments in preclinical PI3Kα H1047R-mutant breast cancer models
    Puca, Loredana
    Dowless, Michele S.
    Perez-Ferreiro, Carmen M.
    Ortiz-Ruiz, Maria Jesus
    Donoho, Gregory P.
    Capen, Andrew
    Huber, Lysiane
    Bogner, Sarah M.
    Fei, Dongling
    Manro, Jason R.
    Yu, Chun Ping
    Xu, Wei Guo
    Wang, Rui
    Chen, Shuang
    Hicks, Mark A.
    Zolfaghari, Parisa
    Faber, Andrew
    Gilmour, Raymond
    Ramstetter, Monica D.
    Chang, Matthew T.
    Lallena, Maria Jose
    Gong, Xuequian
    Hyman, David M.
    Smyth, Lillian M.
    Brandhuber, Barbara J.
    Taylor, Barry S.
    Klippel, Anke
    [J]. CANCER RESEARCH, 2023, 83 (05)
  • [4] Investigating the Structure and Dynamics of the PIK3CA Wild-Type and H1047R Oncogenic Mutant
    Gkeka, Paraskevi
    Evangelidis, Thomas
    Pavlaki, Maria
    Lazani, Vasiliki
    Christoforidis, Savvas
    Agianian, Bogos
    Cournia, Zoe
    [J]. PLOS COMPUTATIONAL BIOLOGY, 2014, 10 (10)
  • [5] Cryo-EM structures reveal two allosteric inhibition modes of PI3Ka H1047R involving a re-shaping of the activation loop
    Huang, Xiuliang
    Wang, Kailiang
    Han, Jing
    Chen, Xiumei
    Wang, Zhenglin
    Wu, Tianlun
    Yu, Bo
    Zhao, Feng
    Wang, Xinjuan
    Li, Huijuan
    Xie, Zhi
    Zhu, Xiaotian
    Zhong, Wenge
    Ren, Xiaoming
    [J]. STRUCTURE, 2024, 32 (07)
  • [6] Investigating the structure and dynamics of the PIK3CA wild-type and H1047R oncogenic mutant for potential allosteric modulation
    Gkeka, Paraskevi
    Papafotika, Alexandra
    Christoforidis, Savvas
    Cournia, Zoe
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2015, 249
  • [7] A phase 1 trial of LOXO-783, a potent, highly mutant-selective, brain-penetrant allosteric PI3Kα H1047R inhibitor in PIK3CA H1047R-mutant advanced breast cancer (aBC) and other solid tumors (PIKASSO-01, trial in progress)
    Juric, Dejan
    Jhaveri, Komal
    Beeram, Muralidhar
    Hamilton, Erika
    Chau, Vincent
    Hanley, Matthew P.
    Liu, Shiyao
    Smyth, Lillian M.
    [J]. CANCER RESEARCH, 2023, 83 (05)
  • [8] Discovery and characterization of OKI-219, an orally bioavailable H1047R-mutant-selective inhibitor of PI3Kα
    Taylor, Molly A.
    Zhao, Qian
    Mareska, David
    Hoh, Maria
    Izrayelit, Yevgeniy
    Litwiler, Kevin
    Boys, Mark L.
    Woessner, Rich
    Walker, Duncan
    Diamond, Jennifer
    Winkler, James D.
    [J]. MOLECULAR CANCER THERAPEUTICS, 2023, 22 (12)
  • [9] Synthesis, biological evaluation and structure-activity relationship of a novel class of PI3Kα H1047R mutant inhibitors
    Zhang, Ning
    Yu, Zhimei
    Yang, Xiaohong
    Zhou, Yan
    Wang, Jia
    Zhang, Shao-Lin
    Wang, Ming-Wei
    He, Yun
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 158 : 707 - 719
  • [10] Discovery of HP567, a highly potent, brain-penetrating, and H1047R-selective PI3K α inhibitor for the treatment of tumors bearing H1047R mutation
    Li, Jing
    Fan, Lei
    Liu, Chengcheng
    Luo, Yao
    Chu, Xiaohui
    Yu, Hua
    Wang, Fei
    Li, Xinghai
    [J]. CANCER RESEARCH, 2024, 84 (07)
12