# Structural pharmacology of Chinese medicine: technological breakthroughs in decoding multi-target synergy and precision mechanisms **Authors:** Caiyan Wang, Yanling Li, Lin Zhuo, Songzhu Xu, Mengyao Wang, Zhongqiu Liu PMC · DOI: 10.1007/s44307-026-00095-x · Advanced Biotechnology · 2026-03-13 ## TL;DR This review explores how modern technologies are helping to understand the complex mechanisms of Traditional Chinese Medicine, enabling its integration into precision medicine. ## Contribution The paper highlights technological breakthroughs in structural pharmacology that decode TCM's multi-target synergy and precision mechanisms. ## Key findings - High-resolution structural techniques and AI-driven modeling are advancing TCM mechanism understanding. - Persistent challenges include capturing transient interactions and modeling multi-component dynamics. - Future research aims to build a predictive foundation for TCM modernization and global application. ## Abstract Traditional Chinese Medicine (TCM) offers valuable therapeutic strategies for chronic and infectious diseases, yet the inherent complexity of its multi-component, multi-target formulations and synergistic effects presents substantial challenges to pharmacological mechanistic understanding. Structural pharmacology of Chinese Medicine has emerged as a transformative discipline, integrating structural biology, computational chemistry, and pharmacology to elucidate the precise mechanisms underlying TCM efficacy. This review synthesizes technological advancements that enable the characterization of synergistic mechanisms and dynamic molecular interactions in TCM. Key advancements include high-resolution structural techniques such as X-ray crystallography, cryo-electron microscopy, sophisticated computational approaches such as AI-driven predictive modeling, and advanced analytical platforms. We critically examine persistent technical hurdles, such as capturing transient binding events and modeling complex multi-component system dynamics. Finally, we outline future research trajectories to establish a predictive and adaptable scientific foundation for TCM modernization, facilitating its evidence-based global integration and application in precision medicine. ## Full-text entities - **Genes:** ORF1ab (ORF1a polyprotein;ORF1ab polyprotein) [NCBI Gene 43740578], NR1H4 (nuclear receptor subfamily 1 group H member 4) [NCBI Gene 9971] {aka BAR, FXR, HRR-1, HRR1, PFIC5, RIP14}, CXCR6 (C-X-C motif chemokine receptor 6) [NCBI Gene 10663] {aka BONZO, CD186, CDw186, STRL33, TYMSTR}, CDH5 (cadherin 5) [NCBI Gene 1003] {aka 7B4, CD144}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, UGCG (UDP-glucose ceramide glucosyltransferase) [NCBI Gene 7357] {aka GCS, GLCT1}, F2R (coagulation factor II thrombin receptor) [NCBI Gene 2149] {aka CF2R, HTR, PAR-1, PAR1, TR}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817] {aka INrf2, KLHL19}, Mpro [NCBI Gene 8673700], ACLY (ATP citrate lyase) [NCBI Gene 47] {aka ACL, ATPCL, CLATP}, ZHX2 (zinc fingers and homeoboxes 2) [NCBI Gene 22882] {aka AFR1, RAF}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, Hif1a (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 29560] {aka HIF1-alpha, MOP1}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, Prkaa2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 78975] {aka Ampk, Ampka2}, Hsp90aa1 (heat shock protein 90 alpha family class A member 1) [NCBI Gene 299331] {aka Hsp86, Hsp90, Hspca}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, Rtn4 (reticulon 4) [NCBI Gene 68585] {aka 1110020G17Rik, ASY, C130026I10Rik, NOGO, NSP-CL, NgA}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, DGKQ (diacylglycerol kinase theta) [NCBI Gene 1609] {aka DAGK, DAGK4, DAGK7}, WARS1 (tryptophanyl-tRNA synthetase 1) [NCBI Gene 7453] {aka GAMMA-2, HMN9, HMND9, IFI53, IFP53, NEDMSBA}, VN1R17P (vomeronasal 1 receptor 17 pseudogene) [NCBI Gene 441931] {aka GPCR}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, ASB2 (ankyrin repeat and SOCS box containing 2) [NCBI Gene 51676] {aka ASB-2}, Cdk6 (cyclin-dependent kinase 6) [NCBI Gene 114483], Ubr5 (ubiquitin protein ligase E3 component n-recognin 5) [NCBI Gene 70790] {aka Edd, Edd1}, CHPF2 (chondroitin polymerizing factor 2) [NCBI Gene 54480] {aka CSGLCA-T, CSGlcAT, ChSy-3, chPF-2}, ALDH1A1 (aldehyde dehydrogenase 1 family member A1) [NCBI Gene 216] {aka ALDC, ALDH-E1, ALDH1, ALDH11, HEL-9, HEL-S-53e}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, BCL2A1 (BCL2 related protein A1) [NCBI Gene 597] {aka ACC-1, ACC-2, ACC1, ACC2, BCL2L5, BFL1}, CYP3A4 (cytochrome P450 family 3 subfamily A member 4) [NCBI Gene 1576] {aka CP33, CP34, CYP3A, CYP3A3, CYPIIIA3, CYPIIIA4}, Ldlr (low density lipoprotein receptor) [NCBI Gene 300438] {aka LDLRA}, HSF1 (heat shock transcription factor 1) [NCBI Gene 3297] {aka HSTF1}, PDE4A (phosphodiesterase 4A) [NCBI Gene 5141] {aka DPDE2, PDE4, PDE46}, PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3) [NCBI Gene 5209] {aka IPFK2, PFK2, iPFK-2}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, CSPG4 (chondroitin sulfate proteoglycan 4) [NCBI Gene 1464] {aka CSPG4A, HMW-MAA, MCSP, MCSPG, MEL-CSPG, MSK16}, Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, ORM2 (orosomucoid 2) [NCBI Gene 5005] {aka AGP-B, AGP-B', AGP2}, COX2 (COXII) [NCBI Gene 26198] {aka COII}, GYPA (glycophorin A (MNS blood group)) [NCBI Gene 2993] {aka CD235a, GPA, GPErik, GPSAT, HGpMiV, HGpMiXI}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, Kdr (kinase insert domain receptor) [NCBI Gene 25589] {aka Vegfr-2}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, GJB2 (gap junction protein beta 2) [NCBI Gene 2706] {aka BAPS, CX26, DFNA3, DFNA3A, DFNB1, DFNB1A}, EPHB2 (EPH receptor B2) [NCBI Gene 2048] {aka BDPLT22, CAPB, DRT, EK5, EPHT3, ERK}, SPR (sepiapterin reductase) [NCBI Gene 6697] {aka SDR38C1}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, BCAT1 (branched chain amino acid transaminase 1) [NCBI Gene 586] {aka BCATC, BCT1, ECA39, MECA39, PNAS121, PP18}, Mul1 (mitochondrial ubiquitin ligase activator of NFKB 1) [NCBI Gene 68350] {aka 0610009K11Rik, Gide, Tnrip-1}, COL9A3 (collagen type IX alpha 3 chain) [NCBI Gene 1299] {aka DJ885L7.4.1, EDM3, IDD, MED, STL6} - **Diseases:** malaria (MESH:D008288), ulcerative colitis (MESH:D003093), deaths (MESH:D003643), cancer (MESH:D009369), LSFM (MESH:D020795), triple-negative breast cancer (MESH:D064726), Myocardial Ischemic Reperfusion Injury (MESH:D015428), Type 2 Diabetes Mellitus (MESH:D003924), pancreatic ductal adenocarcinoma (MESH:D021441), synaptic toxicity (MESH:D012183), APL (MESH:D015473), insulin resistance (MESH:D007333), chronic obstructive pulmonary disease (MESH:D029424), FEL (MESH:D028361), osteosarcoma (MESH:D012516), hepatic fibrosis (MESH:D008103), COVID-19 (MESH:D000086382), colorectal cancer carcinoids (MESH:D015179), pancreatic cancer (MESH:D010190), rheumatoid arthritis (MESH:D001172), fatty liver (MESH:D005234), neurodegenerative (MESH:D019636), inflammation (MESH:D007249), infectious diseases (MESH:D003141), breast cancer (MESH:D001943), toxicity (MESH:D064420), fever (MESH:D005334), asthma (MESH:D001249), Parkinson's disease (MESH:D010300), psoriatic lesions (MESH:D015535), Alzheimer's disease (MESH:D000544), SPCM (MESH:C562377), hepatocellular carcinoma (MESH:D006528), metabolic syndrome (MESH:D024821) - **Chemicals:** carbon (MESH:D002244), lignans (MESH:D017705), imidazole (MESH:C029899), paclitaxel (MESH:D017239), beta-(1 3) glucan (MESH:C033363), Astragaloside IV (MESH:C052064), terpene (MESH:D013729), paeoniflorin (MESH:C015423), puerarin (MESH:C033607), oxygen (MESH:D010100), phenylpropanol (MESH:C439395), amino acids (MESH:D000596), bisdemethoxycurcumin (MESH:C034786), ergosterol (MESH:D004875), BCAA (MESH:D000597), polyketide (MESH:D061065), glutathione (MESH:D005978), sulfhydryl (MESH:D013438), phenol (MESH:D019800), ruthenium (MESH:D012428), Ponicidin (MESH:C090365), alpha-mangostin (MESH:C021053), pyridine (MESH:C023666), EB (MESH:C571217), alpha-MG (MESH:C027020), Artemisinin (MESH:C031327), curcumin (MESH:D003474), Hydrogen (MESH:D006859), ester (MESH:D004952), epoxide (MESH:D004852), chromium (MESH:D002857), ROS (MESH:D017382), magnolol (MESH:C005498), Geniposidic Acid (MESH:C058966), Atractylodin II (-), phenanthrenequinone (MESH:C005399), phenolic acids (MESH:C017616), naphthoquinone (MESH:D009285), benzene (MESH:D001554), water (MESH:D014867), xanthone (MESH:C009689), beta-(1 4)-glucan (MESH:C040088), Deuterium (MESH:D003903), Schiff base (MESH:D012545), sugar (MESH:D000073893), gemcitabine (MESH:D000093542), Indirubin (MESH:C027185), SAB (MESH:C076944), licochalcone A (MESH:C070840), lipid (MESH:D008055), tretinoin (MESH:D014212), nitrogen (MESH:D009584), adriamycin (MESH:D004317), quercetin (MESH:D011794), diterpene alkaloids (MESH:D000077743), polysaccharide (MESH:D011134), sulochrin (MESH:C111298), geodin (MESH:C052047), methyl jasmonate (MESH:C072239), baicalein (MESH:C006680) - **Species:** Coptis chinensis (species) [taxon 261450], Ganoderma lucidum (species) [taxon 5315], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Ephedra sinica (cao ma-huang, species) [taxon 33152], Rattus norvegicus (brown rat, species) [taxon 10116], Monkeypox virus (no rank) [taxon 10244], Pseudostellaria heterophylla (hai er shen, species) [taxon 418402], Salvia miltiorrhiza (Chinese salvia, species) [taxon 226208], Mus musculus (house mouse, species) [taxon 10090], Gammacoronavirus (genus) [taxon 694013], Phellodendron amurense (species) [taxon 68554], Agaricus bisporus (common mushroom, species) [taxon 5341], Homo sapiens (human, species) [taxon 9606] - **Mutations:** G12D, T790M ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12988076/full.md ## Figures 6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12988076/full.md ## References 3 references — full list in the complete paper: https://tomesphere.com/paper/PMC12988076/full.md --- Source: https://tomesphere.com/paper/PMC12988076