- Efficient photocaging of a tight-binding bisubstrate inhibitor of cAMP-dependent protein kinase
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Photocaging of a tight-binding bisubstrate inhibitor of cAMP-dependent protein kinase (PKA) with a nitrodibenzofuran-based group fully abolished its inhibitory potency. The affinity difference between the photocaged and the active inhibitor was over 5 orders of magnitude. The photocaged inhibitor disrupted the PKA holoenzyme in cell lysates upon photolysis under a 398 nm LED.
- S?rmus, Tanel,Lavogina, Darja,Enkvist, Erki,Uri, Asko,Viht, Kaido
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supporting information
p. 11147 - 11150
(2019/09/20)
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- Structural optimization elaborates novel potent Akt inhibitors with promising anticancer activity
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Targeting of Akt has been validated as a well rationalized approach to cancer treatment, and represents a promising therapeutic strategy for aggressive hematologic malignancies. We describe herein an exploration of novel Akt inhibitors for cancer therapy through structural optimization of previously described 4-(piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives. Our studies yielded a novel series of pyrrolopyrimidine based phenylpiperidine carboxamides capable of potent inhibition of Akt1. Notably, 10h exhibited robust antiproliferative effects in both mantle cell lymphoma cell lines and primary patient tumor cells. Low micromolar doses of 10h induced cell apoptosis and cell cycle arrest in G2/M phase, and significantly downregulated the phosphorylation of Akt downstream effectors GSK3β and S6 in Jeko-1 cells.
- Liu, Yang,Yin, Yanzhen,Zhang, Zhen,Li, Carrie J.,Zhang, Hui,Zhang, Daoguang,Jiang, Changying,Nomie, Krystle,Zhang, Liang,Wang, Michael L.,Zhao, Guisen
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p. 543 - 551
(2017/07/12)
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- AXL KINASE INHIBITORS
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Axl kinase inhibitory compounds are disclosed, as well as compositions and methods of using the same in the treatment of cancer and other conditions mediated by and/or associated with Axl kinase.
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Page/Page column 35
(2008/12/08)
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- Monocyclic-7H-pyrrolo[2,3-d]pyrimidine compounds, compositions, and methods of use
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Novel pyrrolo[2,3-d]pyrimidine compounds useful as inhibitors of the enzyme protein tyrosine kinases such as Janus Kinase 3 as well as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases are described.
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Page/Page column 19
(2008/06/13)
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