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Article(id=1308842627047453453, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308842471539442166, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2026-0450, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1776614400000, receivedDateStr=2026-04-20, revisedDate=1780502400000, revisedDateStr=2026-06-04, acceptedDate=null, acceptedDateStr=null, onlineDate=1789981999407, onlineDateStr=2026-09-21, pubDate=1786464000000, pubDateStr=2026-08-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1789981999407, onlineIssueDateStr=2026-09-21, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1789981999407, creator=13701087609, updateTime=1789981999407, updator=13701087609, issue=Issue{id=1308842471539442166, tenantId=1146029695717560320, journalId=1189982191388893191, year='2026', volume='61', issue='8', pageStart='2821', pageEnd='3220', issueExtLink='null', onlineDate='null', pubDate='1786464000000', pubDateStr='2026-08-12', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1789981962332, creator='13701087609', updateTime=1789984137222, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1308851593773150481, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308842471539442166, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1308851593773150482, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308842471539442166, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=3096, endPage=3104, ext={EN=ArticleExt(id=1308842628922307342, articleId=1308842627047453453, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Virtual screening, binding validation and anti-lung squamous cell carcinoma activity of novel NSD3-binding compounds, columnId=1190335348761793317, journalTitle=Acta Pharmaceutica Sinica, columnName=Original Articles, runingTitle=null, highlight=null, articleAbstract=

Nuclear receptor-binding SET domain protein 3 (NSD3) plays an important role in the initiation and progression of lung squamous cell carcinoma (LUSC), whereas small-molecule inhibitors targeting NSD3 remain limited. This study targeted the NSD3-PWWP1 domain and identified 37 potential NSD3-binding compounds through Glide-based hierarchical virtual screening followed by drug-likeness filtering. Surface plasmon resonance (SPR) analysis showed that compounds 2, 4, 20 and 27 could directly bind to NSD3, among which compound 2 exhibited the strongest equilibrium dissociation constant (KD = 0.95 μmol·L-1), approaching that of the positive control BI9321 (0.46 μmol·L-1). Molecular docking analysis indicated that all four candidate compounds could occupy the NSD3-PWWP1 binding pocket and form stable interactions with key residues. At 30 μmol·L-1, the four candidate compounds showed different degrees of inhibitory activity against three NSD3-high LUSC cell lines. Notably, compound 2 displayed a half maximal inhibitory concentration (IC50) of 4.08 ± 1.01 μmol·L-1 in HCC95 cells, which was superior to that of BI9321 (17.62 ± 3.11 μmol·L-1). Meanwhile, these candidate compounds did not show obvious cytotoxicity toward HEK293T cells and exhibited favorable ADMET profiles and physicochemical property distributions. In conclusion, several potential NSD3 inhibitors were identified in this study. Among them, compound 2, a novel coumarin-based scaffold distinct from BI9321, represents a promising lead for further optimization as an anti-LUSC agent.

, authors=Feng-feng GAO, Hua NING*, authorsList=Feng-feng GAO, Hua NING, authorCompany=null, correspAuthors=Hua NING, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2026 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1308842630209958681, articleId=1308842627047453453, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=新型NSD3结合分子的虚拟筛选、结合验证及抗肺鳞癌活性研究, columnId=1190335348896011050, journalTitle=药学学报, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=

核受体结合SET结构域蛋白3 (nuclear receptor-binding SET domain protein 3, NSD3) 在肺鳞癌发生发展中发挥重要作用, 但其小分子抑制剂仍较少。本研究以NSD3-PWWP1结构域为靶点, 采用Glide分级虚拟筛选和成药性过滤后, 共获得37个潜在NSD3结合化合物。表面等离子体共振(surface plasmon resonance, SPR) 结果表明, 化合物2、4、20和27均可与NSD3直接结合, 其中化合物2的结合活性最强(平衡解离常数KD = 0.95 μmol·L-1), 接近阳性对照BI9321 (0.46 μmol·L-1)。分子对接结果显示, 4个候选化合物均可占据NSD3-PWWP1结合口袋并与关键残基形成稳定相互作用。在30 μmol·L-1浓度下, 4个候选化合物对3株NSD3高表达肺鳞癌细胞均表现出不同程度的抑制作用, 其中化合物2对HCC95细胞的IC50 (half maximal inhibitory concentration) 为4.08 ± 1.01 μmol·L-1, 优于BI9321 (17.62 ± 3.11 μmol·L-1)。同时, 候选化合物对HEK293T细胞未表现出明显毒性。综上, 本研究筛选获得了若干可与NSD3-PWWP1结构域结合并具有抗肺鳞癌细胞增殖活性的候选化合物。其中, 化合物2为不同于BI9321的香豆素类新骨架分子, 在靶点结合、细胞活性和初步成药性方面表现较好, 具有进一步优化为抗肺鳞癌先导化合物的潜力。

, authors=高凤凤, 宁华*, authorsList=高凤凤, 宁华, authorCompany=null, correspAuthors=宁华, authorNote=

作者贡献:

高凤凤负责分子对接、生物实验与活性数据整理、分析及论文撰写等; 宁华负责论文指导与修改等工作。

, correspAuthorsNote=
宁华, Tel: 86-10-88196147, E-mail:
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Design, synthesis, and antitumor activity of NSDs inhibitors targeting lung squamous cell carcinoma [J]. Eur J Med Chem, 2025, 289: 117388., articleTitle=null, refAbstract=null), Reference(id=1308842638002975573, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=19, rfOrder=18, authorNames=null, journalName=null, refType=null, unstructuredReference=Luo G, Wang G, Liao CB, et al. Next-generation inhibitors of SARS-CoV-2 Mpro overcome the deficiencies of Paxlovid [J]. Nat Commun, 2026, 17: 4897., articleTitle=null, refAbstract=null), Reference(id=1308842638078473046, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=20, rfOrder=19, authorNames=null, journalName=null, refType=null, unstructuredReference=Cai W, Li Z, Zhao ML, et al. Design, synthesis, and evaluation of phenylpyrrole derivatives as small-molecule activators of BAX [J]. J Med Chem, 2026, 69: 7541-7571., articleTitle=null, refAbstract=null), Reference(id=1308842638158164823, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=21, rfOrder=20, authorNames=null, journalName=null, refType=null, unstructuredReference=Xue MZ, Liang YQ, Yuan Z, et al. Inhibiting RhoA activation via GDP-state stabilization to relieve heart failure [J]. Circ Res, 2026, 138: e327107., articleTitle=null, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1308842630407090970, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, xref=null, ext=[AuthorCompanyExt(id=1308842630415479579, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, companyId=1308842630407090970, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Peking University Cancer Hospital & Beijing Institute for Cancer Prevention and Treatment, Department of Pharmacy Key Laboratory of Carcinogenesis and Translational Research, Beijing 100142, China), AuthorCompanyExt(id=1308842630537114396, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, companyId=1308842630407090970, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=北京大学肿瘤医院暨北京市肿瘤防治研究所药剂科, 恶性肿瘤发病机制及转化研究教育部重点实验室, 北京 100142)])], figs=[ArticleFig(id=1308842633502487345, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=EN, label=null, caption=null, figureFileSmall=RB14XRiTmM92H3mQyVRkCQ==, figureFileBig=ywM/0yUiLmu4qblf/QrmLA==, tableContent=null), ArticleFig(id=1308842633573790514, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=CN, label=Fig.1, caption=Surface plasmon resonance (SPR) analysis confirms direct binding of compounds 2, 4, 20 and 27 to the NSD3-PWWP1 domain. NSD3 protein was immobilized on a CM5 sensor chip by amine coupling, and the interactions between compounds and NSD3 were recorded on a Biacore 8K instrument. BI9321 was used as a positive control. The KD values were obtained by fitting the sensorgrams using the Biacore evaluation software, figureFileSmall=RB14XRiTmM92H3mQyVRkCQ==, figureFileBig=ywM/0yUiLmu4qblf/QrmLA==, tableContent=null), ArticleFig(id=1308842633758339891, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=EN, label=null, caption=null, figureFileSmall=T0MliNM+opnfzI8usMrgtA==, figureFileBig=FQpUA5NjNWGyjg/o5mQvcw==, tableContent=null), ArticleFig(id=1308842633825448756, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=CN, label=Fig.2, caption=Molecular docking models of compounds 2, 4, 20, 27 and BI9321 in the NSD3-PWWP1 binding pocket. Three-dimensional docking poses of compounds 2, 4, 20, 27 and the positive control BI9321 in the binding pocket of NSD3-PWWP1 were generated using Schrödinger Glide XP mode. The docking models were visualized with Maestro. Key interactions, including hydrogen bonding, hydrophobic interactions and aromatic interactions, are shown, figureFileSmall=T0MliNM+opnfzI8usMrgtA==, figureFileBig=FQpUA5NjNWGyjg/o5mQvcw==, tableContent=null), ArticleFig(id=1308842633892557621, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=EN, label=null, caption=null, figureFileSmall=o+s/9aepSN/mo9DBdClePw==, figureFileBig=xBRkKDJxn2V7hqXRPUfyaA==, tableContent=null), ArticleFig(id=1308842633955472182, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=CN, label=Fig.3, caption=Compound 2 shows the best structural overlap with BI9321 in the NSD3-PWWP1 binding pocket. Overlay of docking conformations of compounds 2, 4, 20 and 27 with the co-crystallized ligand BI9321 (blue) in the NSD3-PWWP1 binding pocket. Docking poses were generated using Schrödinger and visualized with Maestro, figureFileSmall=o+s/9aepSN/mo9DBdClePw==, figureFileBig=xBRkKDJxn2V7hqXRPUfyaA==, tableContent=null), ArticleFig(id=1308842634026775351, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=EN, label=null, caption=null, figureFileSmall=4/qp6WTgRuQ7JIR4dAT+tA==, figureFileBig=sdryL27nHfBgQtNDOvRxow==, tableContent=null), ArticleFig(id=1308842634131632952, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=CN, label=Fig.4, caption=Candidate compounds do not show obvious cytotoxicity in HEK293T cells. Cytotoxicity of compounds 2, 4, 20, 27 and BI9321 toward HEK293T cells was evaluated by CCK-8 assay after treatment with compounds at 50 μmol·L-1 for 6 days. Cell viability was calculated relative to the untreated control group. n = 3, $ \overline{x} $ ± s, figureFileSmall=4/qp6WTgRuQ7JIR4dAT+tA==, figureFileBig=sdryL27nHfBgQtNDOvRxow==, tableContent=null), ArticleFig(id=1308842634202936121, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=EN, label=null, caption=null, figureFileSmall=J5gB6wm5UzeDqZ4daD2j3w==, figureFileBig=s4EKvzTHAdRqJ8yKSz7EUQ==, tableContent=null), ArticleFig(id=1308842634265850682, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=CN, label=Fig.5, caption=Comparison of predicted physicochemical properties of candidate compounds and BI9321. Predicted physicochemical properties of compounds 2, 4, 20, 27 and BI9321, including molecular weight, lipophilicity, hydrogen bond donor count, hydrogen bond acceptor count, rotatable bond count and topological polar surface area, were obtained using ADMETlab 3.0, figureFileSmall=J5gB6wm5UzeDqZ4daD2j3w==, figureFileBig=s4EKvzTHAdRqJ8yKSz7EUQ==, tableContent=null), ArticleFig(id=1308842634337153851, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
Compd.IDMWDocking score
13381-0485449.85-10.31
2D154-0426363.46-10.13
3S841-0123446.51-10.08
4E614-0268420.47-10.01
5S629-1410325.37-9.99
65251-2231359.36-9.54
7V020-3118442.48-9.37
8C611-0424463.01-9.32
9V005-5923487.58-9.23
10Y041-4071359.23-9.13
118011-6647365.39-9.05
12S824-2421328.42-8.91
138008-6642314.32-8.85
14Y205-8942422.46-8.84
15S606-0462367.41-8.80
16V031-0095401.49-8.78
17SC07-0375397.48-8.77
18V030-9625436.42-8.62
19G025-0088399.52-8.59
20V004-8936395.42-8.55
21Y043-2271363.42-8.53
223702-0127460.49-8.45
23D256-0112443.53-8.38
24Y512-4404372.43-8.36
25V028-0360435.43-8.35
264100-3375382.42-8.32
27G070-1367419.55-8.26
28SA67-0668352.4-8.24
29D715-0527331.33-8.14
30S751-0135377.41-8.08
31S687-2006419.49-8.08
32Y044-1166337.77-8.03
33C520-0230442.97-7.94
341692-0068428.86-7.92
35Y044-5024448.53-7.87
362279-3516374.48-7.85
37V010-6083461.44-7.85
), ArticleFig(id=1308842634408457020, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=CN, label=Tab.1, caption=

Thirty-seven candidate compounds identified by Glide-based virtual screening. MW: Molecular weight

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Compd.IDMWDocking score
13381-0485449.85-10.31
2D154-0426363.46-10.13
3S841-0123446.51-10.08
4E614-0268420.47-10.01
5S629-1410325.37-9.99
65251-2231359.36-9.54
7V020-3118442.48-9.37
8C611-0424463.01-9.32
9V005-5923487.58-9.23
10Y041-4071359.23-9.13
118011-6647365.39-9.05
12S824-2421328.42-8.91
138008-6642314.32-8.85
14Y205-8942422.46-8.84
15S606-0462367.41-8.80
16V031-0095401.49-8.78
17SC07-0375397.48-8.77
18V030-9625436.42-8.62
19G025-0088399.52-8.59
20V004-8936395.42-8.55
21Y043-2271363.42-8.53
223702-0127460.49-8.45
23D256-0112443.53-8.38
24Y512-4404372.43-8.36
25V028-0360435.43-8.35
264100-3375382.42-8.32
27G070-1367419.55-8.26
28SA67-0668352.4-8.24
29D715-0527331.33-8.14
30S751-0135377.41-8.08
31S687-2006419.49-8.08
32Y044-1166337.77-8.03
33C520-0230442.97-7.94
341692-0068428.86-7.92
35Y044-5024448.53-7.87
362279-3516374.48-7.85
37V010-6083461.44-7.85
), ArticleFig(id=1308842634483954493, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
Compd.Docking scoreHydrogen-bond interactionπ-π/cation-π interactionHydrophobic interactionSalt bridge
2-10.13Ser314Tyr281/Trp284Trp284/
4-10.01Ser314/Gln367/Tyr281Tyr281/Trp284Tyr281/Trp284/Phe312/
20-8.55Ser314/Arg363Tyr281/Trp284/Phe312/Glu318
27-8.26/Tyr281/Trp284Tyr281/Trp284/Phe312/
BI9321-11.02Ser314Tyr281/Trp284Glu318
), ArticleFig(id=1308842634559451966, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=CN, label=Tab.2, caption=

Predicted binding interactions of candidate compounds with NSD3-PWWP1 based on molecular docking

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Compd.Docking scoreHydrogen-bond interactionπ-π/cation-π interactionHydrophobic interactionSalt bridge
2-10.13Ser314Tyr281/Trp284Trp284/
4-10.01Ser314/Gln367/Tyr281Tyr281/Trp284Tyr281/Trp284/Phe312/
20-8.55Ser314/Arg363Tyr281/Trp284/Phe312/Glu318
27-8.26/Tyr281/Trp284Tyr281/Trp284/Phe312/
BI9321-11.02Ser314Tyr281/Trp284Glu318
), ArticleFig(id=1308842634634949439, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
Compd.Inhibition rate at 30 μmol·L-1/%
NCI-H1703NCI-H520HCC95
264.22 ± 5.8792.71 ± 6.5499.92 ± 4.51
456.93 ± 6.7284.21 ± 2.2191.93 ± 5.52
2047.27 ± 7.4749.62 ± 2.7471.01 ± 9.73
2765.16 ± 4.2277.25 ± 6.9889.61 ± 3.41
BI932134.85 ± 7.9356.73 ± 2.7480.15 ± 2.98
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Inhibitory effects of candidate compounds on three NSD3-high LUSC cell lines at 30 μmol·L-1. Cell growth inhibition was determined by CCK-8 assay after treatment with compounds at 30 μmol·L-1 for 6 days. n = 3, $ \overline{x} $ ± s

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Compd.Inhibition rate at 30 μmol·L-1/%
NCI-H1703NCI-H520HCC95
264.22 ± 5.8792.71 ± 6.5499.92 ± 4.51
456.93 ± 6.7284.21 ± 2.2191.93 ± 5.52
2047.27 ± 7.4749.62 ± 2.7471.01 ± 9.73
2765.16 ± 4.2277.25 ± 6.9889.61 ± 3.41
BI932134.85 ± 7.9356.73 ± 2.7480.15 ± 2.98
), ArticleFig(id=1308842634865636161, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
Compd.AbsorptionDistributionMetabolismExcretionToxicity
HIAPPBHLM stability/mint1/2/hRat oral acute toxicity/ mg·kg-1
2≥ 30%98.06%> 300.54> 500
4≥ 30%98.13%> 300.39> 500
20≥ 30%98.34%≤ 300.86> 500
27≥ 30%96.93%≤ 300.41> 500
BI 9321≥ 30%82.64%> 300.38< 500
), ArticleFig(id=1308842634928550722, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842627047453453, language=CN, label=Tab.4, caption=

Absorption, distribution, metabolism, excretion and toxicity (ADMET) evaluation of candidate compounds and BI9321, ADMET properties were predicted using the ADMETlab 3.0 platform. HIA: Human intestinal absorption; PPB: Plasma protein binding; HLM: Human liver microsomal; t1/2: Predicted half-life

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Compd.AbsorptionDistributionMetabolismExcretionToxicity
HIAPPBHLM stability/mint1/2/hRat oral acute toxicity/ mg·kg-1
2≥ 30%98.06%> 300.54> 500
4≥ 30%98.13%> 300.39> 500
20≥ 30%98.34%≤ 300.86> 500
27≥ 30%96.93%≤ 300.41> 500
BI 9321≥ 30%82.64%> 300.38< 500
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新型NSD3结合分子的虚拟筛选、结合验证及抗肺鳞癌活性研究
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高凤凤 , 宁华 *
药学学报 | 研究论文 2026,61(8): 3096-3104
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药学学报 |研究论文 2026 , 61 (8) : 3096 -3104
新型NSD3结合分子的虚拟筛选、结合验证及抗肺鳞癌活性研究
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高凤凤, 宁华*
作者信息
  • 北京大学肿瘤医院暨北京市肿瘤防治研究所药剂科, 恶性肿瘤发病机制及转化研究教育部重点实验室, 北京 100142
通讯作者:
宁华, Tel: 86-10-88196147, E-mail:
作者简介:

作者贡献:

高凤凤负责分子对接、生物实验与活性数据整理、分析及论文撰写等; 宁华负责论文指导与修改等工作。

Virtual screening, binding validation and anti-lung squamous cell carcinoma activity of novel NSD3-binding compounds
Feng-feng GAO, Hua NING*
Affiliations
  • Peking University Cancer Hospital & Beijing Institute for Cancer Prevention and Treatment, Department of Pharmacy Key Laboratory of Carcinogenesis and Translational Research, Beijing 100142, China
出版时间: 2026-08-12 doi: 10.16438/j.0513-4870.2026-0450
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摘要
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核受体结合SET结构域蛋白3 (nuclear receptor-binding SET domain protein 3, NSD3) 在肺鳞癌发生发展中发挥重要作用, 但其小分子抑制剂仍较少。本研究以NSD3-PWWP1结构域为靶点, 采用Glide分级虚拟筛选和成药性过滤后, 共获得37个潜在NSD3结合化合物。表面等离子体共振(surface plasmon resonance, SPR) 结果表明, 化合物2、4、20和27均可与NSD3直接结合, 其中化合物2的结合活性最强(平衡解离常数KD = 0.95 μmol·L-1), 接近阳性对照BI9321 (0.46 μmol·L-1)。分子对接结果显示, 4个候选化合物均可占据NSD3-PWWP1结合口袋并与关键残基形成稳定相互作用。在30 μmol·L-1浓度下, 4个候选化合物对3株NSD3高表达肺鳞癌细胞均表现出不同程度的抑制作用, 其中化合物2对HCC95细胞的IC50 (half maximal inhibitory concentration) 为4.08 ± 1.01 μmol·L-1, 优于BI9321 (17.62 ± 3.11 μmol·L-1)。同时, 候选化合物对HEK293T细胞未表现出明显毒性。综上, 本研究筛选获得了若干可与NSD3-PWWP1结构域结合并具有抗肺鳞癌细胞增殖活性的候选化合物。其中, 化合物2为不同于BI9321的香豆素类新骨架分子, 在靶点结合、细胞活性和初步成药性方面表现较好, 具有进一步优化为抗肺鳞癌先导化合物的潜力。

核受体结合SET结构域蛋白3  /  PWWP1结构域  /  虚拟筛选  /  肺鳞癌  /  小分子抑制剂

Nuclear receptor-binding SET domain protein 3 (NSD3) plays an important role in the initiation and progression of lung squamous cell carcinoma (LUSC), whereas small-molecule inhibitors targeting NSD3 remain limited. This study targeted the NSD3-PWWP1 domain and identified 37 potential NSD3-binding compounds through Glide-based hierarchical virtual screening followed by drug-likeness filtering. Surface plasmon resonance (SPR) analysis showed that compounds 2, 4, 20 and 27 could directly bind to NSD3, among which compound 2 exhibited the strongest equilibrium dissociation constant (KD = 0.95 μmol·L-1), approaching that of the positive control BI9321 (0.46 μmol·L-1). Molecular docking analysis indicated that all four candidate compounds could occupy the NSD3-PWWP1 binding pocket and form stable interactions with key residues. At 30 μmol·L-1, the four candidate compounds showed different degrees of inhibitory activity against three NSD3-high LUSC cell lines. Notably, compound 2 displayed a half maximal inhibitory concentration (IC50) of 4.08 ± 1.01 μmol·L-1 in HCC95 cells, which was superior to that of BI9321 (17.62 ± 3.11 μmol·L-1). Meanwhile, these candidate compounds did not show obvious cytotoxicity toward HEK293T cells and exhibited favorable ADMET profiles and physicochemical property distributions. In conclusion, several potential NSD3 inhibitors were identified in this study. Among them, compound 2, a novel coumarin-based scaffold distinct from BI9321, represents a promising lead for further optimization as an anti-LUSC agent.

nuclear receptor-binding SET domain protein 3  /  PWWP1 domain  /  virtual screening  /  lung squamous cell carcinoma  /  small-molecule inhibitor
高凤凤, 宁华. 新型NSD3结合分子的虚拟筛选、结合验证及抗肺鳞癌活性研究. 药学学报, 2026 , 61 (8) : 3096 -3104 . DOI: 10.16438/j.0513-4870.2026-0450
Feng-feng GAO, Hua NING. Virtual screening, binding validation and anti-lung squamous cell carcinoma activity of novel NSD3-binding compounds[J]. Acta Pharmaceutica Sinica, 2026 , 61 (8) : 3096 -3104 . DOI: 10.16438/j.0513-4870.2026-0450
正文
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肺癌是严重威胁人类健康的恶性肿瘤之一, 其中肺鳞癌(lung squamous cell carcinoma, LUSC) 是非小细胞肺癌的重要组成部分[1, 2]。与肺腺癌相比, 肺鳞癌可用于临床精准治疗的分子靶点相对有限, 患者总体治疗选择仍较为受限, 因此开发针对肺鳞癌的新型治疗靶点及候选药物具有重要意义。近年来, 表观遗传调控异常在肺鳞癌发生发展中的作用受到广泛关注, 相关表观遗传调控蛋白也逐渐成为抗肿瘤药物研发的重要方向[3]。
核受体结合SET结构域蛋白3 (nuclear receptor-binding SET domain protein 3, NSD3) 是NSD家族的重要成员, 具有组蛋白赖氨酸甲基转移酶相关结构域, 可通过调控染色质状态和基因转录参与肿瘤细胞增殖、分化及转移等多种生物学过程[4-6]。研究表明, NSD3在多种恶性肿瘤中异常表达, 并与肿瘤进展密切相关。尤其在肺鳞癌中, NSD3被认为是具有致癌驱动作用的关键表观遗传调控因子, 其高表达或功能激活可促进肿瘤细胞生长并维持恶性表型。因此, 靶向NSD3有望为肺鳞癌治疗提供新的干预策略[7-10]。
从结构与功能上看, NSD3蛋白含有PWWP、PHD及SET等多个功能结构域, 其中PWWP结构域可介导蛋白与甲基化组蛋白及染色质的识别, 在NSD3募集至染色质和发挥转录调控作用过程中具有重要意义[11-13]。相较于直接靶向催化结构域, 针对PWWP结构域的小分子配体筛选为开发NSD3调控剂提供了新的思路。已有研究报道了首个具有较好活性和选择性的NSD3-PWWP1拮抗剂BI9321[14], 该化合物可作为研究NSD3功能的重要化学探针, 也为后续先导化合物发现提供了参考。尽管如此, 目前针对NSD3的小分子抑制剂研究总体仍较少[15-18], 可同时兼顾靶点结合能力、细胞活性与初步成药性的候选分子仍有待进一步发掘。
虚拟筛选因具有高效、低成本和可快速聚焦优势化学骨架等特点, 已成为早期药物发现的重要技术手段[19]。结合表面等离子体共振(surface plasmon resonance, SPR) 技术, 可进一步从生物物理层面验证候选化合物与靶蛋白之间的直接相互作用, 并结合分子对接、细胞活性及成药性预测实现对候选分子的多维度评价[20, 21]。基于此, 本研究以NSD3为靶点, 采用Glide虚拟筛选从化合物库中筛选潜在结合分子, 并通过SPR实验、分子对接、肺鳞癌细胞增殖抑制实验、正常细胞毒性评价及吸收、分布、代谢、排泄和毒性(absorption, distribution, metabolism, excretion and toxicity, ADMET) 预测, 对候选化合物进行系统分析, 旨在发现具有潜力的新型NSD3结合分子, 为肺鳞癌靶向药物的进一步优化和开发提供实验依据。
结果与讨论
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1　分级虚拟筛选获得37个符合成药性要求的NSD3潜在结合化合物
为筛选能够与NSD3-PWWP1结构域结合的小分子化合物, 本研究基于NSD3-PWWP1蛋白晶体结构(PDB: 6G2O), 采用Schrödinger软件对ChemDiv化合物库中约160万个小分子进行了逐级虚拟筛选。首先, 依据利平斯基五规则(Lipinski's rule of five) 对化合物库进行初步过滤, 以提高候选分子的类药性; 随后, 采用Glide模块, 依次按照高通量虚拟筛选(high throughput virtual screening, HTVS)、标准精度筛选(standard precision, SP) 和高精度筛选(extra precision, XP) 3个阶段进行逐级筛选, 每轮保留评分排名前10%的化合物进入下一轮筛选; XP精筛结束后, 进一步结合ADMETlab 3.0剔除含有泛干扰化合物结构(pan-assay interference compounds, PAINS) 的分子。
在此基础上, 结合对接评分、配体与NSD3-PWWP1结合口袋关键残基的相互作用方式及化合物结构多样性, 对候选分子进行人工复筛, 最终获得37个潜在NSD3结合化合物, 其基本信息见表1。结果表明, 基于分级虚拟筛选结合成药性预测的策略, 能够从大规模化合物库中有效富集具有潜在结合活性且具备一定类药性特征的候选分子, 为后续SPR结合实验和细胞活性评价提供了化合物基础。
2　SPR证实4个小分子与NSD3具有较高亲和力结合
为验证虚拟筛选结果, 采用SPR技术检测候选化合物与NSD3-PWWP1结构域的结合能力。结果显示, 化合物2、4、20和27均可与NSD3发生浓度依赖性结合, 其平衡解离常数(KD) 分别为0.95、1.62、9.08和5.88 μmol·L-1 (图1)。其中, 香豆素(coumarin) 骨架化合物2的结合活性最强, 接近阳性对照BI9321的0.46 μmol·L-1, 表明作者通过虚拟筛选不仅获得了能够有效结合NSD3-PWWP1的候选分子, 还发现了具有进一步优化潜力的新骨架化合物。
3　分子对接的关键相互作用残基
为分析候选化合物与NSD3-PWWP1结构域的潜在结合模式, 对SPR活性较好的化合物2、4、20、27及阳性对照BI9321进行了分子对接。以6G2O中BI9321的共晶结合构象为参考, 结果显示(表2), 这些化合物在对接模型中均可进入NSD3-PWWP1的甲基赖氨酸识别口袋, 并与口袋关键残基形成潜在氢键、π-π/阳离子-π、电荷-电荷或盐桥等作用, 提示其可能具有与NSD3-PWWP1结合的结构基础。已报道的BI9321能够与NSD3-PWWP1芳香笼中的氨基酸Tyr281和Trp284形成π-π相互作用, 并且与Ser314和Glu318形成关键氢键/离子键相互作用。
进一步分析发现, 4个候选化合物与BI9321的结合模式总体相似, 均可较好地占据PWWP1芳香笼口袋, 并与多个关键残基形成静电作用或氢键作用, 从而稳定结合于NSD3-PWWP1口袋(图2)。其中, 化合物2在口袋中的构象更为合理, 且与BI9321表现出较好的构象叠合效果(图3)。化合物2的香豆素母核可与芳香笼区域形成较好的疏水或芳香相互作用, 并与Ser314形成关键氢键, 提示其作为不同于BI9321的新型香豆素类先导骨架具有进一步优化潜力, 这一结果与SPR检测结果一致。
4　候选化合物对3株NSD3高表达肺鳞癌细胞的增殖抑制作用
为评价候选化合物的体外抗肺鳞癌活性, 采用CCK-8法检测30 μmol·L-1浓度下4个候选化合物及阳性对照BI9321对NCI-H1703、NCI-H520和HCC95 3株NSD3高表达肺鳞癌细胞增殖的抑制作用(表3)。结果显示, 4个候选化合物对3株肺鳞癌细胞均具有不同程度的抑制活性, 但抑制效果存在明显差异。
其中, 化合物2表现出最优的细胞抑制活性, 对NCI-H1703、NCI-H520和HCC95细胞的抑制率分别为(64.22 ± 5.87)%、(92.71 ± 6.54)%和(99.92 ± 4.51)%, 均高于阳性对照BI9321的(34.85 ± 7.93)%、(56.73 ± 2.74)%和(80.15 ± 2.98)%。化合物4和27也表现出较好的抑制作用, 尤其在NCI-H520和HCC95细胞中抑制率较高; 相比之下, 化合物20的细胞抑制活性相对较弱。
5　候选化合物在HCC95细胞中表现出优于BI9321的抑制活性
由于HCC95细胞对候选化合物整体更为敏感, 进一步采用CCK-8法检测4个候选化合物及阳性对照BI9321对HCC95细胞的半数抑制浓度(half maximal inhibitory concentration, IC50)。结果显示, 化合物2、4、20和27对HCC95细胞的IC50分别为4.08 ± 1.01、8.95 ± 0.37、18.92 ± 2.17和8.16 ± 1.33 μmol·L-1, 而BI9321的IC50为17.62 ± 3.11 μmol·L-1。化合物2表现出最强的细胞抑制活性, 其IC50最低, 明显优于阳性对照BI9321; 化合物4和27也表现出较好的抑制作用, 其IC50均低于BI9321; 相比之下, 化合物20的活性相对较弱, 与BI9321接近。上述结果表明, 虚拟筛选获得的候选化合物中, 尤其是化合物2具有较好的抗肺鳞癌活性, 可作为后续结构优化和机制研究的重点分子。
6　候选化合物对HEK293T非肿瘤细胞的初步毒性评价
为初步评价候选化合物的细胞毒性风险, 采用CCK-8法检测50 μmol·L-1浓度下4个候选化合物及阳性对照BI9321对HEK293T非肿瘤细胞活力的影响。由于HEK293T细胞不能代表正常肺上皮细胞, 本实验仅用于早期非肿瘤细胞毒性初筛。筛选结果显示, 在相同处理条件下, 化合物2、4、20和27处理后HEK293T细胞存活率总体处于较高水平, 未见明显细胞毒性(图4)。其中, 化合物2和27处理后细胞存活率与BI9321接近, 化合物20处理后细胞存活率略低, 但总体仍维持在较高水平, 化合物4处理后细胞存活率最高, 提示其对正常细胞影响较小。结合前述肺鳞癌细胞抑制实验结果可见, 化合物2、4和27在保持较低正常细胞毒性的同时, 对NSD3高表达肺鳞癌细胞表现出较好的抑制活性, 提示其具有进一步研究和优化的潜力。
7　候选化合物ADMET预测及理化性质分析
为初步评价候选化合物的成药性, 对4个候选化合物及阳性对照BI9321进行了ADMET预测分析(表4)。结果显示, 4个候选化合物预测人体肠道吸收(human intestinal absorption, HIA) 水平均≥ 30%, 提示其可能具有一定吸收潜力。然而, 候选化合物预测血浆蛋白结合(plasma protein binding, PPB) 较高, 为96.93%~98.34%, 提示其游离药物比例可能较低; 同时, 其预测半衰期为0.39~0.86 h, 提示体内暴露时间可能有限。ADMETlab 3.0预测可为早期结构优化提供参考, 但尚不能直接证明候选化合物具有良好的体内药代动力学性质。后续仍需通过体外代谢稳定性、血浆蛋白结合率及体内药代动力学实验进一步验证。
进一步对候选化合物的理化性质进行比较分析(图5) 发现, 4个候选化合物的分子质量、脂水分配系数、氢键供体数、氢键受体数、可旋转键数和拓扑极性表面积等参数总体分布于类药性合理范围内。总体来看, 化合物2和4在结合活性、细胞抑制活性及ADMET特征之间表现出较好的平衡, 尤其化合物2兼具较强的NSD3结合能力、较优的抗肺鳞癌活性及可接受的成药性特征, 提示其具有进一步作为先导化合物开展结构优化的潜力。
结论
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NSD3是肺鳞癌中具有重要研究价值的表观遗传调控靶点, 其异常扩增或高表达与肿瘤细胞增殖、存活及恶性表型维持密切相关。近年来, 针对NSD3的小分子化学探针研究逐渐受到关注, 其中靶向PWWP1结构域的BI9321为NSD3功能研究提供了重要工具。然而, 目前NSD3抑制剂总体报道仍较少, 尤其是兼具靶点结合能力、细胞活性和初步成药性的候选分子仍有待进一步发现。本研究以NSD3-PWWP1结构域为靶点, 构建了“虚拟筛选-SPR验证-分子对接-细胞活性评价-ADMET预测”的筛选流程, 从约160万个化合物中获得37个候选分子, 并进一步筛选出4个与NSD3具有较好结合活性的化合物, 其中化合物2表现最优。
本研究结果表明, 基于结构的虚拟筛选结合SPR生物物理验证, 是发现NSD3-PWWP1小分子配体的有效策略。4个候选化合物均可与NSD3直接结合, 提示虚拟筛选具有较好的命中效率。进一步的分子对接结果显示, 这些化合物均可占据NSD3-PWWP1的芳香笼口袋, 并与关键残基形成稳定相互作用, 其中化合物2与BI9321具有较好的构象叠合, 同时保留了与关键残基的有利相互作用。值得注意的是, 化合物2属于不同于BI9321的香豆素类骨架, 提示本研究不仅获得了新的NSD3结合分子, 而且发现了可用于后续结构优化的新型先导骨架。这一点对于拓展NSD3-PWWP1配体的化学空间具有一定意义。
除靶点结合能力外, 候选化合物的细胞活性也是评价其先导价值的重要指标。本研究发现, 4个候选化合物均对3株NSD3高表达肺鳞癌细胞表现出不同程度的抑制作用, 其中化合物2的活性最强, 在HCC95细胞中的IC50明显优于BI9321, 说明其不仅具有较好的体外结合能力, 还能够在细胞水平发挥更强的抑制作用。与此同时, 化合物2、4和27对HEK293T细胞未表现出明显毒性, 提示其具有一定的选择性窗口。ADMET预测进一步显示, 候选化合物总体具有较好的口服吸收潜力和较低的急性毒性风险, 其中化合物2在结合活性、细胞活性和成药性特征之间表现出较好的平衡。因此, 化合物2可作为后续围绕NSD3靶点开展构效关系研究和先导优化的重点分子。
需要指出的是, 本研究目前主要从体外生物物理结合、分子模拟和细胞增殖抑制层面评价候选化合物的活性, 尚不能完全证明其细胞抑制作用由NSD3靶向作用直接介导。后续研究需进一步开展NSD3敲低或过表达、CETSA、蛋白互作下拉实验(pull-down)、竞争结合实验及NSD3下游表观遗传标志物和转录调控网络分析, 以明确候选化合物在细胞内的靶点占有情况及其抗肺鳞癌作用的靶点依赖性; 其次, 本研究主要进行了细胞增殖抑制评价, 尚未进一步阐明候选化合物是否通过阻断NSD3染色质识别功能进而影响下游转录调控网络; 再次, ADMET结果基于计算预测, 仍需结合体外代谢稳定性、药代动力学及体内药效实验进一步验证。后续研究可围绕化合物2的香豆素骨架开展系统构效关系优化, 并结合靶点结合、表观遗传调控和体内外药效实验, 进一步评价其作为抗肺鳞癌先导化合物的应用潜力。
实验部分
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1　虚拟筛选
采用Schrödinger软件对ChemDiv化合物库中的约160万个小分子化合物进行虚拟筛选。首先依据利平斯基五规则对化合物库进行初步过滤, 以提高候选分子的类药性。以NSD3-PWWP1结构域晶体结构为受体蛋白, 蛋白结构坐标文件下载自Protein Data Bank, PDB编号6G2O。对受体蛋白进行预处理后, 基于配体结合口袋建立对接网格, 随后按照Schrödinger Glide标准流程开展分级筛选。
虚拟筛选分为HTVS、SP和XP 3个阶段。每一轮筛选均保留评分排名前10%的化合物进入下一轮, 以逐步缩小候选化合物范围并提高筛选准确性。XP精筛结束后, 进一步结合ADMETlab 3.0剔除含有PAINS警示结构的分子。随后对候选分子进行人工复筛, 筛选标准包括: ① Glide docking score排名靠前; ②分子能够合理占据NSD3-PWWP1甲基赖氨酸识别口袋; ③与芳香笼区域或Ser314、Glu318等关键残基形成潜在氢键、疏水作用、π-π作用或静电作用; ④化合物骨架具有一定结构多样性, 避免候选分子过度集中于单一化学类型; ⑤化合物具有商业可获得性, 并具备后续SPR和细胞实验验证的可行性。最终筛选获得37个候选化合物用于后续实验验证。
2　SPR分析
采用SPR技术检测候选化合物与NSD3-PWWP1结构域蛋白的结合能力。所有实验均在Biacore 8K仪器上进行, 使用CM5传感芯片。首先采用pH 4.0的乙酸钠缓冲液将NSD3蛋白稀释至100 ng·μL-1, 随后通过氨基偶联法将其固定于CM5芯片表面, 固定水平约为15 000 RU。参比通道仅进行活化和封闭处理, 不固定NSD3-PWWP1蛋白, 用于扣除背景信号及非特异性吸附。实验采用PBS-P作为运行缓冲液。候选化合物及阳性对照化合物BI9321先用二甲基亚砜(dimethyl sulfoxide, DMSO) 配制成储备液, 再将运行缓冲液稀释为不同浓度梯度, 样品中DMSO终体积分数均为5%。同时配制DMSO体积分数为4.5%~5.8%的校准溶液, 用于溶剂校正。
待基线稳定后, 将不同浓度梯度的化合物依次注入流路系统, 使其流经固定有NSD3-PWWP1蛋白的芯片表面, 实时记录化合物与蛋白相互作用产生的结合和解离信号。实验数据采用Biacore 8K配套软件进行处理, 首先扣除参比通道信号, 并结合DMSO校正结果消除溶剂效应, 获得真实响应值。根据不同浓度化合物的传感曲线特征评价其与NSD3-PWWP1蛋白的相互作用能力, 并筛选出结合活性较好的候选化合物用于后续分子对接及细胞活性评价。
3　分子对接分析
采用Schrödinger软件对SPR检测中结合活性较好的4个候选化合物及阳性对照化合物BI9321与NSD3-PWWP1结构域的结合模式进行分子对接分析。根据对接结果, 结合Glide打分及配体与靶蛋白关键氨基酸残基之间的相互作用方式, 对候选化合物在NSD3-PWWP1结合口袋中的构象进行分析。重点考察候选化合物与口袋关键残基之间形成的氢键作用、疏水作用、π-π堆积及阳离子-π相互作用等, 以评价其潜在结合能力。各化合物与NSD3-PWWP1结构域的三维结合模式采用Maestro软件进行可视化展示。
4　细胞培养及肺鳞癌细胞增殖的增殖抑制评价和初步细胞毒性评价
人肺鳞癌细胞NCI-H520、NCI-H1703和HCC95采用RPMI-1640培养基培养, 培养基中加入10%胎牛血清和1%双抗, 配制成完全培养基, 于37 ℃、5% CO2细胞培养箱中常规培养。取对数生长期细胞消化后接种于96孔板中, 每孔接种1 000个细胞, 待细胞贴壁后加入候选化合物或阳性对照化合物BI9321进行处理。候选化合物均以DMSO配制储备液, 并用完全培养基稀释至相应工作浓度; 各给药组及溶剂对照组中DMSO终体积分数保持一致。细胞以低密度接种后进行连续6天处理, 处理期间每3天更换一次含相同浓度化合物或等体积DMSO的新鲜完全培养基, 以评价化合物对肺鳞癌细胞连续增殖过程的抑制作用。实验过程中设置空白孔、细胞对照孔和等体积DMSO溶剂对照孔。在初筛实验中, 参考候选化合物的SPR亲和力、溶解性及早期小分子细胞活性筛选常用浓度范围, 选择30 μmol·L-1作为统一筛选浓度, 用于比较不同候选化合物对肺鳞癌细胞增殖的相对抑制作用。对于HEK293T细胞毒性评价, 选择50 μmol·L-1作为较高测试浓度, 以初步观察候选化合物在高浓度条件下的细胞毒性风险。所有给药组均设置等体积DMSO溶剂对照, 且DMSO终体积分数保持一致。
处理结束后, 采用细胞计数试剂盒-8 (cell counting kit-8, CCK-8) 检测细胞活力。按照试剂说明书向各孔加入CCK-8工作液, 孵育适当时间后, 于酶标仪检测450 nm波长处吸光度(A) 值。根据公式(1) 和(2) 分别计算细胞抑制率和细胞存活率:
$\begin{array}{l}{\rm{细胞抑制率}} \ (\%)=\left(A_{\text {对照 }}-A_{\text {实验 }}\right) /\left(A_{\text {对照 }}-A_{\text {空白 }}\right) \times \\\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ 100\%\end{array}$
$\begin{array}{l}{\rm{细胞存活率}} \ (\%)=\left(A_{\text {实验 }}-A_{\text {空白 }}\right) /\left(A_{\text {对照 }}-A_{\text {空白 }}\right) \times \\\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ 100 \%\end{array}$
IC50采用GraphPad Prism 9.5.1软件进行剂量-效应曲线拟合。
5　候选化合物的ADMET及理化性质预测
采用ADMETlab3.0在线工具对候选化合物及阳性对照化合物BI9321进行ADMET性质预测, 并对其理化性质进行评估。将各化合物的二维结构输入ADMETlab 3.0平台, 获得与药物开发相关的参数, 包括吸收、分布、代谢、排泄及毒性等指标, 用于初步评价候选化合物的成药性特征。
同时, 对候选化合物及BI9321的相对分子质量、脂水分配系数、氢键供体数、氢键受体数、可旋转键数、拓扑极性表面积等理化性质参数进行预测和比较分析。结合ADMET预测结果与理化性质参数, 综合评价候选化合物的类药性及进一步结构优化潜力。

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doi: 10.16438/j.0513-4870.2026-0450
  • 接收时间：2026-04-20
  • 首发时间：2026-09-21
  • 出版时间：2026-08-12
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  • 收稿日期：2026-04-20
  • 修回日期：2026-06-04
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    北京大学肿瘤医院暨北京市肿瘤防治研究所药剂科, 恶性肿瘤发病机制及转化研究教育部重点实验室, 北京 100142

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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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