3MJW

PI3 Kinase gamma with a benzofuranone inhibitor

3MJW の概要

• エントリーDOI: 10.2210/pdb3mjw/pdb
• 分子名称: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, (2Z)-4,6-dihydroxy-2-[(8-methoxy-1,2,3,4-tetrahydropyrazino[1,2-a]indol-10-yl)methylidene]-1-benzofuran-3(2H)-one (2 entities in total)
• 機能のキーワード: atp-binding, kinase, nucleotide-binding, transferase
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 111134.54

構造登録者

Bard, J.,Svenson, K. (登録日: 2010-04-13, 公開日: 2010-06-09, 最終更新日: 2023-09-06)

主引用文献

Zhang, N.,Ayral-Kaloustian, S.,Anderson, J.T.,Nguyen, T.,Das, S.,Venkatesan, A.M.,Brooijmans, N.,Lucas, J.,Yu, K.,Hollander, I.,Mallon, R.
5-Ureidobenzofuranone indoles as potent and efficacious inhibitors of PI3 kinase-alpha and mTOR for the treatment of breast cancer.
Bioorg.Med.Chem.Lett., 20:3526-3529, 2010

PubMed Abstract: A series of 5-ureidobenzofuran-3-one indoles as potent inhibitors of PI3Kalpha and mTOR has been developed. The best potency in cells was obtained when the urea group was extended to a 4-[2-(dimethylamino)ethyl]methylamino amidophenyl group. A 7-fluoro group on the indole ring also enhanced cellular potency. Compound 18i, incorporating the optimal functional groups, showed high potency in cellular lines and was further studied in vivo. It was able to inhibit the biomarker phosphorylation for 8h when dosed at 25 mg/kg iv. In the MDA-MB-361 breast cancer model, it shrank the tumor size remarkably when dosed at 25 mg/kg iv on days 1, 5, and 9.

PubMed: 20483602
DOI: 10.1016/j.bmcl.2010.04.139

実験手法

X-RAY DIFFRACTION (2.87 Å)