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Evaluating the Molecular Effects of Two Quinoline-Containing Anti-Proliferative Compounds Using a Multi-Omics Approach

ABSTRACT: Cancer is a major health concern worldwide, necessitating the discovery of more targeted approaches adequate management and therapy of tumors that are especially malignant, such as triple-negative breast cancer (TNBC). Through various biochemical studies carried out on TNBC, the MAPK pathway was implicated in cancer progression. MAPK involves the activation of multiple kinases, one of which is the C-RAF kinase. Therefore, small-molecule kinase inhibitors that can inhibit C-RAF and the MAPK pathway are of great interest in cancer research. This study investigates two C-RAF kinase inhibitors synthesized as quinoline-containing small molecules based on the design of the established kinase inhibitor sorafenib and other lead compounds. MDA-MB-468 and BT-549, both TNBC cell lines, were treated with the compounds separately and in combination, followed by metabolomics and proteomics analyses using LC-MS/MS. Upon identifying altered metabolic pathways and dysregulated proteins, the compounds’ mechanisms of action were found to involve DNA damage and repair, tRNA synthesis, protein expression, and energy production. The combination of the two C-RAF kinase inhibitors on TNBC cell lines led to earlier impact on amino acid metabolism and subsequent protein expression. This study hopes to enrich the current understanding of cancer biochemistry and reveal key biomarkers which can ultimately be targeted cancer therapies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Core Facility

LAB HEAD: Prof. Mohammad Semreen

PROVIDER: PXD073897 | Pride | 2026-04-12

REPOSITORIES: Pride

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			Action	DRS
	BT-549_1_combined.zip	Other
	BT-549_2_combined.zip	Other
	C1-14674.d.zip	Other
	C2-14675.d.zip	Other
	C3-14676.d.zip	Other

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