PXD054680-1

PXD054680 is an original dataset announced via ProteomeXchange.

Title	In silico approach and mass spectrometry-based proteome profiling unravel IGF-1R inhibition potential of 3-(2-furoyl)-indole scaffolds in hepatocellular carcinoma
Description	Considering the multi-targeting potential of furan-indole hybrids as anticancer agents, this study aimed to unveil the mechanism of new 3-(2-furoyl)-indole derivatives for their cytotoxicy on hepatocellular carcinoma cells. Initially, we conducted an in vitro cytotoxicity assay for thirteen 3-(2-furoyl)-indole derivatives on HepG2 and MCF-7 cells using MTT assay, correlating the results with in silico screening of the selected drug targets. Among them, compounds 4a, 4b, and 4c demonstrated better selectivity towards HepG2 cells than MCF-7 cells. This was in good agreement with docking studies, which showed the high binding affinity of compound 4a to the Chain A of IGF-1R at Ile1160, Glu 1080, Met 1082 and Asp-1086, similar to reference ligand. Molecular dynamic study inferred the stable and high binding affinity of compound 4a to IGF-1R. The RMSD and RMSF values were found to be acceptable, and accordingly, a pharmacophore model was constructed. Hence, we conducted label-free quantitative proteome profiling of HepG2 cells treated with active compounds using an in-solution trypsin digestion procedure followed by high-resolution mass spectrometric analysis. We noticed that compound 4a targets IGF-1R pathway by dysregulation of proteins such as SHC-transforming protein 1(P29353), Mitogen-activated protein kinase kinase 3 isoform B variant (Q53EZ9), dual specificity mitogen-activated protein kinase kinase 4 (P45985), stress-activated protein kinase JNK (A0A286YF97), and mitogen-activated protein kinase (E9PQW4). In addition, the apoptotic activities of 4a, 4b, and 4c were studied against HepG2 cells using FACS. These findings are in good agreement with our in silico results, proteome profiling, and also earlier reports on indole compounds. Furthermore, we predicted the in silico ADMET property of the compounds.
HostingRepository	PRIDE
AnnounceDate	2026-03-09
AnnouncementXML	Submission_2026-03-08_18:02:37.329.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD054680
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	RAMALINGAM PERAMAN
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-07 12:18:46	ID requested
⏵ 1	2026-03-08 18:02:38	announced

10.6019/PXD054680;

Myrsing E, Mouli HMC, Nikhil P, Deepali, Sahu A, Jana A, Ramalingam P, Protein profiling uncovers IGF-1R inhibition potential of 3-(2-furoyl)-indole scaffolds in hepatocellular carcinoma. Future Med Chem, 17(5):513-528(2025) [pubmed]

10.1080/17568919.2025.2467616;

submitter keyword: IGF-1R, Hepatocellular carcinoma, Label-free proteomics,3-(2-furoyl)-indole, EGFR

Dr. P. Ramalingam
contact affiliation	Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, 844102, Bihar, India
contact email	drramalingamp@gmail.com
lab head
RAMALINGAM PERAMAN
contact affiliation	National Institute of Pharmaceutical Education and Research, Hajipur
contact email	drramalingamp@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054680
     1. Label: PRIDE project
     2. Name: In silico approach and mass spectrometry-based proteome profiling unravel IGF-1R inhibition potential of 3-(2-furoyl)-indole scaffolds in hepatocellular carcinoma