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Proteome profiling of MOLM-13 cells treated with proposed CK1α 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 each of these compounds (SJ001010039, SJ001010040, SJ001010041, SJ001010047, SJ001010050) degrades CK1α in this cell line and may degrade other proteins. Our aims are to confirm that CK1α is degraded by treatment with each of these compounds and to identify any additional proteins that are targeted for degradation by these compounds.

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: PXD045228 | Pride | 2023-12-01

REPOSITORIES: Pride

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			Action	DRS
	KlcoGrp_f01.1.pepXML	Pepxml
	KlcoGrp_f01.raw	Raw
	KlcoGrp_f02.1.pepXML	Pepxml
	KlcoGrp_f02.raw	Raw
	KlcoGrp_f03.1.pepXML	Pepxml

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

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 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.

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2024-01-04 | PXD045327 | Pride

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