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Direct-to-biology: Accelerated E3 ligase modulator discovery

ABSTRACT: Quatintative analysis of the effects of the E14 compound on the proteome of MM.1S cells.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell

SUBMITTER: Valeriia Sapozhnikova

LAB HEAD: Philipp Mertins

PROVIDER: PXD046752 | Pride | 2024-01-26

REPOSITORIES: Pride

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			Action	DRS
	20230814_E14results.csv	Csv
	Exp_design.txt	Txt
	Janice_20230810_VS_HS_dia_E14comp_01.raw	Raw
	Janice_20230810_VS_HS_dia_E14comp_02.raw	Raw
	Janice_20230810_VS_HS_dia_E14comp_03.raw	Raw

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Publications

Direct-to-biology, automated, nano-scale synthesis, and phenotypic screening-enabled E3 ligase modulator discovery.

Wang Zefeng Z Shaabani Shabnam S Gao Xiang X Ng Yuen Lam Dora YLD Sapozhnikova Valeriia V Mertins Philipp P Krönke Jan J Dömling Alexander A

Nature communications 20231219 1

Thalidomide and its analogs are molecular glues (MGs) that lead to targeted ubiquitination and degradation of key cancer proteins via the cereblon (CRBN) E3 ligase. Here, we develop a direct-to-biology (D2B) approach for accelerated discovery of MGs. In this platform, automated, high throughput, and nano scale synthesis of hundreds of pomalidomide-based MGs was combined with rapid phenotypic screening, enabling an unprecedented fast identification of potent CRBN-acting MGs. The small molecules w ...[more]

PMID: 38114468

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