Isoform-selective PI3K inhibitors as novel therapeutics for the treatment of acute myocardial infarction

被引：19

作者：

Doukas, J. ^{[1
]}

Wrasidlo, W. ^{[1
]}

Noronha, G. ^{[1
]}

Dneprovskaia, E. ^{[1
]}

Hood, J. ^{[1
]}

Soll, R. ^{[1
]}

机构：

[1] TargeGen Inc, San Diego, CA 92121 USA

来源：

BIOCHEMICAL SOCIETY TRANSACTIONS | 2007年 / 35卷

关键词：

inflammation; ischaemia; myocardial infarction; oedema; phosphoinositide 3-kinase (PI3K);

D O I：

10.1042/BST0350204

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the present paper, we review the preclinical development of TG100-115, a PI3K (phosphoinositide 3kinase) gamma/delta isoform-specific inhibitor currently in clinical trials for the reduction of acute MI (myocardial infarction). An overview is presented outlining the pathogenesis of acute MI and the rationale for clinical use of PI3K gamma/delta-specific inhibitors in this indication. TG100-115's broad anti-inflammatory activities are described, as well as its ability to discriminate between cellular signalling pathways downstream of receptor tyrosine kinase ligands such as vascular endothelial growth factor. Finally, we review TG100-115's potent cardioprotective activities as revealed in rigorous animal models of acute MI, and, based on these data, this compound's potential for clinical utility.

引用

页码：204 / 206

页数：3

共 50 条

[1] PI3K Isoform-Selective Inhibitors in Cancer
Duncan, Leslie
Shay, Chloe
Teng, Yong
SINGLE-CELL SEQUENCING AND METHYLATION: METHODS AND CLINICAL APPLICATIONS, 2020, 1255 : 165 - 173
[2] Isoform-Selective PI3K Inhibitors for Various Diseases
Bheemanaboina, Rammohan R. Y.
CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2020, 20 (12) : 1074 - 1092
[3] Improving the Armamentarium of PI3K Inhibitors with Isoform-Selective Agents: A new Light in the Darkness
Rodon, Jordi
Tabernero, Josep
CANCER DISCOVERY, 2017, 7 (07) : 666 - 669
[4] PI3K isoform-selective inhibitors: next-generation targeted cancer therapies
Xiang Wang
Jian Ding
Ling-hua Meng
Acta Pharmacologica Sinica, 2015, 36 : 1170 - 1176
[5] PI3K isoform-selective inhibitors: next-generation targeted cancer therapies
Wang, Xiang
Ding, Jian
Meng, Ling-hua
ACTA PHARMACOLOGICA SINICA, 2015, 36 (10) : 1170 - 1176
[6] L-Aminoacyl-triazine Derivatives Are Isoform-Selective PI3Kβ Inhibitors That Target Nonconserved Asp862 of PI3Kβ
Pinson, Jo-Anne
Zheng, Zhaohua
Miller, Michelle S.
Chalmers, David K.
Jennings, Ian G.
Thompson, Philip E.
ACS MEDICINAL CHEMISTRY LETTERS, 2013, 4 (02): : 206 - 210
[7] Isoform-selective targeting of PI3K: time to consider new opportunities?
Cirillo, Davide
Diceglie, Marta
Nazare, Marc
TRENDS IN PHARMACOLOGICAL SCIENCES, 2023, 44 (09) : 601 - 621
[8] A deep learning-based theoretical protocol to identify potentially isoform-selective PI3Kα inhibitors
Shafiq, Muhammad
Sherwani, Zaid Anis
Mushtaq, Mamona
Nur-e-Alam, Mohammad
Ahmad, Aftab
Ul-Haq, Zaheer
MOLECULAR DIVERSITY, 2024, 28 (04) : 1907 - 1924
[9] Combination studies using PI3K isoform-selective inhibitors in PTEN-deficient cancer cells
Blackwell, Christina
De Young, M. Phillip
CANCER RESEARCH, 2016, 76
[10] Synergistic effects of connexin 43 inhibitor and PI3K isoform-selective inhibitors in temozolomide-resistant glioblastoma
Hutchings, Kasen R.
Pridham, Kevin J.
Liu, Min
Owens, Joseph
Sheng, Zhi
CANCER RESEARCH, 2022, 82 (12)

← 1 2 3 4 5 →