# Target fishing: from “needle in haystack” to “precise guidance”--new technology, new strategy and new opportunity

**Authors:** Juan Chen, Yafei Guo, Jing Shao, Mei Guo, Xinyu Zhu

PMC · DOI: 10.3389/fphar.2025.1673688 · Frontiers in Pharmacology · 2025-11-07

## TL;DR

This paper reviews new technologies like AI and deep learning that are transforming drug target discovery from broad screening to precise identification.

## Contribution

The paper introduces a novel framework integrating deep learning and knowledge graphs for accurate and interpretable drug target prediction.

## Key findings

- Deep learning and knowledge graph integration improves target prediction accuracy.
- The framework enables multi-omics data modeling and clinical decision support.
- It bridges basic research and clinical application for precision drug development.

## Abstract

Drug target discovery is the core breakthrough point of new drug research and development. The chemical complexity and biological network regulation characteristics of natural product systems with a long history of clinical application pose a challenge to the traditional single-target research paradigm. Although traditional technologies based on molecular docking and chemical probes are still dominant, breakthroughs in disruptive technologies such as artificial intelligence and deep learning are driving the transformation of research methods from ‘broad-spectrum screening’ to ‘precise capture’. This review systematically discusses the latest progress of drug target capture technology. Studies have shown that the deep integration of deep learning and knowledge graph not only significantly improves the accuracy of target prediction, but also constructs an interdisciplinary collaboration network across chemical informatics, systems biology and clinical medicine. The fusion of this technology shows three core advantages: multi-dimensional drug-target interaction analysis ability based on deep representation learning; integrate the dynamic predictive modeling ability of multi-omics data; and the interpretable decision support ability with clinical transformability. The purpose of this paper is to provide a theoretical framework for the academic community, and to build a bridge from basic research to clinical application, so as to promote the development of precision drugs into a new era of intelligent drive.

## Full-text entities

- **Genes:** Hspd1-ps3 (heat shock protein 1 (chaperonin), pseudogene 3) [NCBI Gene 432551] {aka Gm12141, Hspd1-1p}, Keap1 (kelch-like ECH-associated protein 1) [NCBI Gene 50868] {aka INRF2, mKIAA0132}, MSRB1 (methionine sulfoxide reductase B1) [NCBI Gene 51734] {aka HSPC270, SELENOR, SELENOX, SELR, SELX, SEPX1}, TRAF2 (TNF receptor associated factor 2) [NCBI Gene 7186] {aka MGC:45012, RNF117, TRAP, TRAP3}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Bax (BCL2-associated X protein) [NCBI Gene 12028], BACE1 (beta-secretase 1) [NCBI Gene 23621] {aka ASP2, BACE, HSPC104}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, Akr1b1 (aldo-keto reductase family 1 member B) [NCBI Gene 11677] {aka ALR2, AR, Ahr-1, Ahr1, Akr1b3, Aldor1}, JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Lonp1 (lon peptidase 1, mitochondrial) [NCBI Gene 74142] {aka 1200017E13Rik, LON, Prss15}, Lrpprc (leucine-rich PPR-motif containing) [NCBI Gene 72416] {aka 3110001K13Rik, Gp130, Lrp130, Lsfc}, ACHE (acetylcholinesterase (Yt blood group)) [NCBI Gene 43] {aka ACEE, ARACHE, N-ACHE, YT}, MCL1 (MCL1 apoptosis regulator, BCL2 family member) [NCBI Gene 4170] {aka BCL2L3, EAT, MCL1-ES, MCL1L, MCL1S, Mcl-1}, Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}, Hspd1 (heat shock protein 1 (chaperonin)) [NCBI Gene 15510] {aka 60kDa, CPN60, HSP-60, HSP-65, Hsp60}, DGKQ (diacylglycerol kinase theta) [NCBI Gene 1609] {aka DAGK, DAGK4, DAGK7}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, UCP1 (uncoupling protein 1) [NCBI Gene 7350] {aka SLC25A7, UCP}, BTK (Bruton tyrosine kinase) [NCBI Gene 695] {aka AGMX1, AT, ATK, BPK, IGHD3, IMD1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}
- **Diseases:** diabetic (MESH:D003920), Leishmaniasis (MESH:D007896), cancer (MESH:D009369), Alzheimer's disease (MESH:D000544), deafness (MESH:D003638), prostate cancer (MESH:D011471), neurodegenerative diseases (MESH:D019636), inflammatory (MESH:D007249), obesity (MESH:D009765), AKI (MESH:D058186), osteoporosis (MESH:D010024), insulin resistance (MESH:D007333), cough (MESH:D003371), ototoxicity (MESH:D006311), toxicity (MESH:D064420), ACs (OMIM:612348), malaria parasites (MESH:D008288), diffuse large B-cell lymphoma (MESH:D016403), hepatocellular carcinoma (MESH:D006528), breast cancer (MESH:D001943), kidney diseases (MESH:D007674), chronic constipation (MESH:D003248)
- **Chemicals:** Tiliroside (MESH:C052083), Trastuzumab (MESH:D000068878), Brentuximab vedotin (MESH:D000079963), alisol B (MESH:C457232), alkaloids (MESH:D000470), biotin (MESH:D001710), dipeptides (MESH:D004151), Polatuzumab vedotin (MESH:C000600736), metformin (MESH:D008687), ibrutinib (MESH:C551803), Trastuzumab emtansine (MESH:D000080044), napabucasin (MESH:C000621033), Gemtuzumab ozogamicin (MESH:D000079982), captopril (MESH:D002216), celastrol (MESH:C050414), atractylenolide II (MESH:C458582), MC (MESH:C061001), curcumin (MESH:D003474), Bavachinin (MESH:C468752), AfBPP (-), Cisplatin (MESH:D002945), Inotuzumab ozogamicin (MESH:D000080045), hydrogen (MESH:D006859), Spiro-acridine (MESH:C000632136), berberine (MESH:D001599), flavonoids (MESH:D005419), Benzophenone (MESH:C047723), ATP (MESH:D000255), Glycopentalone (MESH:C000608030), Lenvatinib (MESH:C531958), Diazirine (MESH:D003978), triclosan (MESH:D014260)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Pseudomonas aeruginosa (species) [taxon 287], Candida albicans (species) [taxon 5476], Marantodes pumilum [taxon 2516552], Escherichia coli (E. coli, species) [taxon 562], Human immunodeficiency virus 1 (no rank) [taxon 11676], Dipteris wallichii (species) [taxon 2909690], Lycium shawii (species) [taxon 155082], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Mycobacterium tuberculosis (species) [taxon 1773], Glycosmis pentaphylla (species) [taxon 76967], Staphylococcus aureus (species) [taxon 1280], Homo sapiens (human, species) [taxon 9606], Aloe vera (acibar, species) [taxon 34199], Danio rerio (leopard danio, species) [taxon 7955], Artocarpus anisophyllus (species) [taxon 709036]
- **Mutations:** A2A

## Full text

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## Figures

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## References

101 references — full list in the complete paper: https://tomesphere.com/paper/PMC12635624/full.md

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Source: https://tomesphere.com/paper/PMC12635624