A practical “preTACs-cytoblot” platform accelerates the streamlined development of PROTAC-based protein degraders DOI

Zijian Rao,

Kailin Li, Ju-Eun Hong

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 251, P. 115248 - 115248

Published: March 7, 2023

Language: Английский

Absence of CDK12 in oocyte leads to female infertility DOI Creative Commons
Denisa Jansová,

Veronika Sedmikova,

Fatima J. Berro

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 27, 2025

Language: Английский

Citations

0
Transcriptional cyclin-dependent kinases: Potential drug targets in cancer therapy DOI
Yi Liu, Leilei Fu, Junhao Wu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 229, P. 114056 - 114056

Published: Dec. 16, 2021

Language: Английский

Citations

25
Discovery of ZLC491 as a Potent, Selective, and Orally Bioavailable CDK12/13 PROTAC Degrader DOI Creative Commons
Licheng Zhou,

Kaijie Zhou,

Yu‐Sun Chang

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(20), P. 18247 - 18264

Published: Oct. 10, 2024

Selective degradation of cyclin-dependent kinases 12 and 13 (CDK12/13) emerges as a new potential therapeutic approach for triple-negative breast cancer (TNBC) other human cancers. While several proteolysis-targeting chimera (PROTAC) degraders CDK12/13 were reported, none are orally bioavailable. Here, we report the discovery ZLC491 potent, selective, bioavailable PROTAC degrader. The compound effectively degraded CDK12 CDK13 with DC50 values 32 28 nM, respectively, in TNBC MDA-MB-231 cells. Global proteomic assessment mechanistic studies revealed that selectively induced cereblon- proteasome-dependent manner. Furthermore, molecule efficiently suppressed transcription expression long genes, predominantly subset genes associated DNA damage response, significantly inhibited proliferation multiple cell lines. Importantly, achieved an oral bioavailability 46.8% rats demonstrated potent vivo degradative effects on xenografted mouse model.

Language: Английский

Citations

3
Current progress and novel strategies that target CDK12 for drug discovery DOI

Peng Lei,

Jifa Zhang, Pei‐Yu Liao

et al.

European Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 240, P. 114603 - 114603

Published: July 12, 2022

Language: Английский

Citations

15
A practical “preTACs-cytoblot” platform accelerates the streamlined development of PROTAC-based protein degraders DOI

Zijian Rao,

Kailin Li, Ju-Eun Hong

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 251, P. 115248 - 115248

Published: March 7, 2023

Language: Английский

Citations

7