Beyond PI3Ks: targeting phosphoinositide kinases in disease.
Beyond PI3Ks: targeting phosphoinositide kinases in disease.
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DOI：
10.1038/s41573-022-00582-5
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发表时间：
2023-05
影响因子：
120.1
通讯作者：
Hammond, Gerald R., V
中科院分区：
文献类型：
--
作者：
Burke, John E.;Triscott, Joanna;Emerling, Brooke M.;Hammond, Gerald R., V
脂质磷酸肌醇是细胞生命和死亡的几乎所有方面的主要调节剂，并且由磷酸肌醇激酶的严格调节活性产生。尽管广泛的努力集中在药物I类磷酸肌醇3-激酶（PI 3 K）上，但近年来已经揭示了靶向人类疾病（包括癌症、免疫缺陷、病毒感染和神经退行性疾病）中的几乎所有磷酸肌醇激酶的机会。这导致了在磷酸肌醇激酶的有效和选择性抑制剂的临床开发中的广泛努力。这篇综述总结了我们目前对磷脂酰肌醇激酶参与疾病的分子基础的理解，并评估了磷脂酰肌醇激酶抑制剂的临床前和临床开发。治疗靶向磷酸肌醇激酶（PIK）超过I类PI 3 K的潜力正日益被认识到。在此，Burke等人描述了I类PI 3 K以外的所有临床相关PIK的结构、功能、调节和在疾病中的作用，评估了开发中的强效和特异性小分子抑制剂。
Lipid phosphoinositides are master regulators of almost all aspects of a cell’s life and death and are generated by the tightly regulated activity of phosphoinositide kinases. Although extensive efforts have focused on drugging class I phosphoinositide 3-kinases (PI3Ks), recent years have revealed opportunities for targeting almost all phosphoinositide kinases in human diseases, including cancer, immunodeficiencies, viral infection and neurodegenerative disease. This has led to widespread efforts in the clinical development of potent and selective inhibitors of phosphoinositide kinases. This Review summarizes our current understanding of the molecular basis for the involvement of phosphoinositide kinases in disease and assesses the preclinical and clinical development of phosphoinositide kinase inhibitors. The potential of therapeutically targeting phosphoinositide kinases (PIKs) beyond the class I PI3Ks is increasingly being realized. Here, Burke et al. describe the structure, function, regulation and roles in disease of all clinically relevant PIKs outside of the class I PI3Ks, assessing potent and specific small-molecule inhibitors in development.
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DOI：
10.1126/science.1243292
发表时间：
2013-11-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Angulo I;Vadas O;Garçon F;Banham-Hall E;Plagnol V;Leahy TR;Baxendale H;Coulter T;Curtis J;Wu C;Blake-Palmer K;Perisic O;Smyth D;Maes M;Fiddler C;Juss J;Cilliers D;Markelj G;Chandra A;Farmer G;Kielkowska A;Clark J;Kracker S;Debré M;Picard C;Pellier I;Jabado N;Morris JA;Barcenas-Morales G;Fischer A;Stephens L;Hawkins P;Barrett JC;Abinun M;Clatworthy M;Durandy A;Doffinger R;Chilvers ER;Cant AJ;Kumararatne D;Okkenhaug K;Williams RL;Condliffe A;Nejentsev S
通讯作者：
Nejentsev S
影响因子：
16.6
作者：
Bilanges B;Alliouachene S;Pearce W;Morelli D;Szabadkai G;Chung YL;Chicanne G;Valet C;Hill JM;Voshol PJ;Collinson L;Peddie C;Ali K;Ghazaly E;Rajeeve V;Trichas G;Srinivas S;Chaussade C;Salamon RS;Backer JM;Scudamore CL;Whitehead MA;Keaney EP;Murphy LO;Semple RK;Payrastre B;Tooze SA;Vanhaesebroeck B
通讯作者：
Vanhaesebroeck B
影响因子：
8.2
作者：
Alliouachene S;Bilanges B;Chaussade C;Pearce W;Foukas LC;Scudamore CL;Moniz LS;Vanhaesebroeck B
通讯作者：
Vanhaesebroeck B
影响因子：
7.7
作者：
Al-Ramahi I;Giridharan SSP;Chen YC;Patnaik S;Safren N;Hasegawa J;de Haro M;Wagner Gee AK;Titus SA;Jeong H;Clarke J;Krainc D;Zheng W;Irvine RF;Barmada S;Ferrer M;Southall N;Weisman LS;Botas J;Marugan JJ
通讯作者：
Marugan JJ
影响因子：
8.8
作者：
Alliouachene S;Bilanges B;Chicanne G;Anderson KE;Pearce W;Ali K;Valet C;Posor Y;Low PC;Chaussade C;Scudamore CL;Salamon RS;Backer JM;Stephens L;Hawkins PT;Payrastre B;Vanhaesebroeck B
通讯作者：
Vanhaesebroeck B