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TMT analysis of MOLM-13 cells treated with series 3 CK1a degraders

ABSTRACT: Targeted Protein Degradation (TPD) encompasses two approaches that generate small molecules with similar proteasome-dependent mechanisms of action: Proteolysis-Targeting Chimeras (PROTACs) and Molecular Glues (MGs). Our goal is to develop novel MG approaches that exploit the E3 ubiquitin ligase Cereblon (CRBN) to degrade key oncogenic drivers in the leading causes of childhood cancer death: acute myeloid leukemia (AML). This project will identify new vulnerabilities and compounds that degrade hitherto undruggable transcription factors in high-risk acute leukemia (AL) and medulloblastoma (MB). Based on our preliminary data, we hypothesize that these compounds target AML cells via CK1a degradation. Our aims are to understand the mechanism by which compounds SJ001041330, SJ001043149, and SJ001043301 target AML cells using TMT proteomic approach and confirm CK1a degradation by these compounds leading to AML cell death.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Yingxue Fu

LAB HEAD: Junmin Peng

PROVIDER: PXD045230 | Pride | 2023-12-01

REPOSITORIES: Pride

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			Action	DRS
	TMT_channel.txt	Txt
	checksum.txt	Txt
	rankgrp_103122_mgtmt_f01.1.pepXML	Pepxml
	rankgrp_103122_mgtmt_f01.raw	Raw
	rankgrp_103122_mgtmt_f02.1.pepXML	Pepxml

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Project description:Targeted Protein Degradation (TPD) encompasses two approaches that generate small molecules with similar proteasome-dependent mechanisms of action: Proteolysis-Targeting Chimeras (PROTACs) and Molecular Glues (MGs). Our goal is to develop novel MG approaches that exploit the E3 ubiquitin ligase Cereblon (CRBN) to degrade key oncogenic drivers in the leading causes of childhood cancer death: acute myeloid leukemia (AML). This project will identify new vulnerabilities and compounds that degrade hitherto undruggable transcription factors in high-risk acute leukemia (AL) and medulloblastoma (MB). Based on our preliminary data, we hypothesize that compound SJ001007095 targets AML cells independent of GSPT1 degradation. Our aims are to understand the mechanism by which compound SJ001007095 targets AML cells using TMT proteomic approach and identify proteins targeted by the compound SJ001007095 leading to their degradation and consequently AML cell death.

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