7QK0

Crystal structure of human BCL6 BTB domain in complex with compound 12a

7QK0 の概要

• エントリーDOI: 10.2210/pdb7qk0/pdb
• 分子名称: B-cell lymphoma 6 protein, (2~{S})-10-[[5-chloranyl-2-[(3~{S},5~{R})-3-methyl-5-oxidanyl-piperidin-1-yl]pyrimidin-4-yl]amino]-2-cyclopropyl-3,3-bis(fluoranyl)-7-methyl-2,4-dihydro-1~{H}-[1,4]oxazepino[2,3-c]quinolin-6-one, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: inhibitor, transcription
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17361.81

構造登録者

Gunnell, E.A.,Le Bihan, Y.-V.,van Montfort, R.L.M. (登録日: 2021-12-17, 公開日: 2022-06-15, 最終更新日: 2024-01-31)

主引用文献

Huckvale, R.,Harnden, A.C.,Cheung, K.J.,Pierrat, O.A.,Talbot, R.,Box, G.M.,Henley, A.T.,de Haven Brandon, A.K.,Hallsworth, A.E.,Bright, M.D.,Akpinar, H.A.,Miller, D.S.J.,Tarantino, D.,Gowan, S.,Hayes, A.,Gunnell, E.A.,Brennan, A.,Davis, O.A.,Johnson, L.D.,de Klerk, S.,McAndrew, C.,Le Bihan, Y.V.,Meniconi, M.,Burke, R.,Kirkin, V.,van Montfort, R.L.M.,Raynaud, F.I.,Rossanese, O.W.,Bellenie, B.R.,Hoelder, S.
Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 In Vivo .
J.Med.Chem., 65:8191-8207, 2022

PubMed Abstract: The transcriptional repressor BCL6 is an oncogenic driver found to be deregulated in lymphoid malignancies. Herein, we report the optimization of our previously reported benzimidazolone molecular glue-type degrader to , a highly potent probe suitable for sustained depletion of BCL6 . We observed a sharp degradation SAR, where subtle structural changes conveyed the ability to induce degradation of BCL6. showed modest efficacy in a lymphoma xenograft mouse model following oral dosing.

PubMed: 35653645
DOI: 10.1021/acs.jmedchem.1c02175

実験手法

X-RAY DIFFRACTION (1.96 Å)