化合物筛选
筛选库的设计基于ChEMBL数据库(v35),该版本数据库包含:
- 1,929,473 compound records
- 2,496,335 compounds
- 21,123,501 annotated activities
- 1,740,546 assays
- 16,003 targets
初始数据集经过自动与人工双重筛选整理,并完成数据聚类。每个条目均附有其化合物报告卡和生物活性摘要的链接。通过LCMS和/或NMR分析数据确认化合物纯度均高于90%。
活性谱分析
所提供的生物活性化合物集合中,目标活性记录满足以下标准:
- Inhibition ≥ 25 %
- Ki ≤ 10 µM
- EC50 ≤ 10 µM
- CC50 ≤ 10 µM
- Kd ≤ 10 µM
- Potency ≤ 10 µM
- XC50 ≤ 10 µM
- Residual Activity ≤ 50 %
- AC50 ≤ 10 µM
- IZ > 10 mm
- MIC ≤ 10 µg/mL
- MIC ≤ 10 µM
高阶生物活性筛选子集中的高活性化合物(筛选标准:活性值<1µM,抑制率>70%),以及针对特定靶点类型与治疗领域的聚焦子集,均可根据需求提供。
图1. 通过筛选内部数据库中的化合物,对参与重要细胞过程的蛋白质产生抑制作用的示例。
靶点分析
已排除与治疗无关的实体。下文列出了化合物库中物质已显示活性的部分蛋白靶点示例:
- 11-beta-hydroxysteroid dehydrogenase 1, 2
- 15-hydroxyprostaglandin dehydrogenase [NAD+]
- 3-phosphoinositide dependent protein kinase-1
- 4'-phosphopantetheinyl transferase ffp
- 5'-nucleotidase
- 6-phospho-1-fructokinase
- 78 kDa glucose-regulated protein
- Acetolactate synthase
- Acetylcholinesterase
- Acinetobacter baumannii
- Acyl coenzyme A:cholesterol acyltransferase
- Acyl-CoA desaturase
- Adenosine receptor (A1, A2a, A2b, A3)
- Adenosylmethionine-8-amino-7-oxononanoate aminotransferase
- Adenylate cyclase type VIII
- Adrenergic receptor alpha-1, beta
- Advanced glycosylation end product-specific receptor
- Aldehyde dehydrogenase
- Aldo-keto reductase family 1 member C1, C3
- Aldose reductase
- ALK tyrosine kinase receptor
- Alkaline phosphatase
- Alpha glucosidase
- Alpha trans-inducing protein (VP16)
- Alpha-1a adrenergic receptor (1a, 2a, 2c)
- Alpha-glucosidase MAL12
- AMP-activated protein kinase, AMPK
- Amyloid-beta A4 protein
- Anandamide amidohydrolase
- Androgen Receptor
- Anoctamin-1
- Apelin receptor
- Apoptotic protease-activating factor 1
- Arachidonate lipoxygenase (15, 5)
- Aryl hydrocarbon receptor
- Ataxin-2
- ATPase family AAA domain-containing protein 5
- ATP-binding cassette sub-family G member 2
- ATP-dependent Clp protease proteolytic subunit
- ATP-dependent DNA helicase Q1
- ATP-dependent molecular chaperone HSP82
- ATP-dependent RNA helicase DDX3X
- Bcl-2-related protein A1
- Bcr/Abl fusion protein
- Benomyl/methotrexate resistance protein
- Beta Lactamase
- Beta adrenergic receptor (1-3)
- Beta-glucuronidase
- Beta-hexosaminidase
- Beta-lactamase AmpC
- Beta-secretase 1
- Bifunctional protein GlmU
- Bile acid receptor FXR
- Bloom syndrome protein
- Brain adenylate cyclase 1
- Branched-chain-amino-acid aminotransferase
- Breast cancer type 1 susceptibility protein
- Bromodomain adjacent to zinc finger domain protein 2B
- Bromodomain-containing protein (2-4, 9)
- Butyrylcholinesterase
- CAAX prenyl protease 1, 2
- Calpain 2
- Cannabinoid receptor (CB1, CB2)
- Carbonic anhydrase
- Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1
- Casein kinase
- Caspase
- Cathepsin B
- C-C chemokine receptor type 3, 5
- CDC7/DBF4 (Cell division cycle 7-related protein kinase/Activator of S phase kinase)
- CDGSH iron-sulfur domain-containing protein 1
- CDK8/Cyclin C
- Chitinase
- Cholesterol 24-hydroxylase
- Cholesteryl ester transfer protein
- Cholinesterase
- Chromobox protein homolog 1
- Chromodomain Y-like protein
- c-Jun N-terminal kinase 1-3
- Coagulation factor III
- Coagulation factor XII
- Connector enhancer of kinase suppressor of ras 1
- Corticotropin-releasing factor receptor 2/Corticotropin-releasing factor-binding protein
- CREB-binding protein
- Cyclic nucleotide specific phosphodiesterase
- Cyclin-dependent kinase 2, 7
- Cyclooxygenase
- Cystathionine beta-lyase metC
- Cystic fibrosis transmembrane conductance regulator
- Cystine/glutamate transporter
- Cystinyl aminopeptidase
- Cytochrome P450
- Cytohesin-2
- Cytoplasmic zinc-finger protein
- D-3-phosphoglycerate dehydrogenase
- D-alanine--D-alanine ligase
- D-alanylalanine synthetase
- D-amino-acid oxidase
- D-aspartate oxidase
- dCTP pyrophosphatase 1
- Death-associated protein kinase 3
- Dehydrogenase/reductase SDR family member 9
- Delta-aminolevulinic acid dehydratase
- Diacylglycerol kinase alpha
- Diamine oxidase
- Dihydrofolate reductase
- Dihydrolipoyl dehydrogenase
- Dihydroorotate dehydrogenase
- Dipeptidyl peptidase IV
- DNA (cytosine-5)-methyltransferase 1
- DNA damage-inducible transcript 3 protein
- DNA dC->dU-editing enzyme APOBEC-3F/3G
- DNA polymerase beta, eta, iota, kappa
- DNA repair and recombination protein RAD54/51/52
- DNA repair protein REV1
- DNA topoisomerase I, II alpha
- DNA-(apurinic or apyrimidinic site) lyase
- Dopamine beta-hydroxylase
- Dopamine D4 receptor
- Dopamine transporter
- Dual specificity phosphatase 22
- Dual specificity protein kinase CLK1, CLK4
- Dual specificity protein phosphatase 1, 3
- Dual-specificity tyrosine-phosphorylation regulated kinase 1A
- Dynamin-1
- Ectonucleotide pyrophosphatase/phosphodiesterase family member 2
- Elongation of very long chain fatty acids protein 6
- Endoplasmic reticulum aminopeptidase 1, 2
- Endothelial PAS domain-containing protein 1
- Endothelin receptor ET-B
- Endothelin-converting enzyme 2
- Enoyl-[acyl-carrier-protein] reductase (FabI)
- Enoyl-[acyl-carrier-protein] reductase [NADH]
- Enoyl-acyl carrier reductase
- Enteropeptidase
- Envelope polyprotein GP160
- Ephrin type-A/B receptor 4
- Epidermal growth factor receptor erbB1
- Epoxide hydratase
- Epoxide hydrolase
- Estradiol 17-beta-dehydrogenase 1, 2
- Estradiol 17-beta-dehydrogenase 2
- Estrogen receptor alpha, beta, gamma
- FAD-linked sulfhydryl oxidase ALR
- Fatty acid binding protein
- Fatty acid synthase
- Fibroblast growth factor 22, 1
- Flap endonuclease 1
- Formyl peptide receptor 1
- Free fatty acid receptor 1
- Fructose-bisphosphatase
- G protein-coupled receptor 44, 6
- GABA transporter 1, 3, 4
- GABA-A receptor
- Galactocerebrosidase
- Galanin receptor 3
- Genome polyprotein
- Glucagon-like peptide 1 receptor
- Glucocorticoid receptor
- Glucose transporter
- Glucose-6-phosphate 1-dehydrogenase
- Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase
- Glutamate [NMDA] receptor
- Glutaminase kidney isoform, mitochondrial
- Glutaminyl-peptide cyclotransferase
- Glutathione-independent formaldehyde dehydrogenase
- Glycogen phosphorylase, muscle form
- Glycogen synthase kinase-3 alpha, beta
- Glycoprotein hormones alpha chain
- Glycosyltransferase-like protein LARGE1
- G-protein coupled receptor 1-3, 35, 55
- GTP-binding nuclear protein
- Guanine nucleotide-binding protein G
- Heat shock factor protein
- Hematopoietic cell protein-tyrosine phosphatase
- Heme oxygenase 1
- Hepatitis C virus serine protease, NS3/NS4A
- Hepatocyte growth factor receptor
- Hexose transporter 1
- High-affinity choline transporter
- Histamine H(1-4) receptor
- Histidine-tRNA ligase
- Histone acetyltransferase GCN5, p300, RTT109
- Histone deacetylase
- Histone-lysine N-methyltransferase
- Human immunodeficiency virus type 1 (integrase, protease, transcriptase, Tat protein)
- Hydroxycarboxylic acid receptor 2
- Hypoxia-inducible factor 1 alpha
- Indoleamine 2,3-dioxygenase
- Indolethylamine N-methyltransferase
- Induced myeloid leukemia cell differentiation protein Mcl-1
- Inhibitor of nuclear factor kappa B kinase beta subunit
- Inosine-5'-monophosphate dehydrogenase
- Insulin-degrading enzyme
- Insulin-like growth factor I receptor
- Integrin alpha-L
- Interleukin-8
- Ionotropic glutamate receptor NMDA 1/2D
- Isocitrate dehydrogenase [NADP] cytoplasmic
- Kappa opioid receptor
- Kinesin-like protein 1
- Krueppel-like factor 5, 10
- Kynurenine 3-monooxygenase
- L-asparaginase
- Lethal(3)malignant brain tumor-like protein 1
- Leucine-rich repeat serine/threonine-protein kinase 2
- Leukocyte elastase
- Leukotriene A4 hydrolase
- Likely tRNA 2'-phosphotransferase
- LIM domain kinase 1
- L-lactate dehydrogenase A chain
- L-methionine gamma-lyase
- Luciferase
- Luciferin 4-monooxygenase
- Lysine-specific demethylase 4A, 4B, 4D, 5B
- Lysine-tRNA ligase
- Lysophosphatidic acid receptor Edg-4
- Lysosomal alpha-glucosidase
- Lysyl oxidase homolog 2
- M14, M17, M18, M21 aminopeptidase
- Macrophage migration inhibitory factor
- Macrophage-stimulating protein receptor
- MAP kinase
- Matriptase
- Matrix metalloproteinase 2, 3, 8, 9
- Melatonin receptor
- Menin/Histone-lysine N-methyltransferase MLL
- Metabotropic glutamate receptor 1, 4, 5
- Methionine aminopeptidase
- Methionyl-tRNA synthetase
- Microphthalmia-associated transcription factor
- Microtubule-associated protein tau
- Mitochondrial import inner membrane translocase subunit TIM10, TIM23
- Mitogen-activated protein kinase
- Monoamine oxidase A, B
- Monocarboxylate transporter 1
- Monoglyceride lipase
- Mucosa-associated lymphoid tissue lymphoma translocation protein 1
- Muscarinic acetylcholine receptor M1, M2, M4, M5
- Myc proto-oncogene protein
- Myeloperoxidase
- NAD-dependent deacetylase sirtuin 1, 2, 6
- N-arachidonyl glycine receptor
- Neuronal acetylcholine receptor
- Neuropeptide S/Y receptor
- Neutrophil cytosol factor 1
- N-glycosylase/DNA lyase
- Nicotinamide phosphoribosyltransferase
- Niemann-Pick C1 protein
- Nitric oxide synthase
- Nociceptin receptor
- Nonstructural protein 1
- Norepinephrine transporter
- Nuclear factor
- Nuclear receptor
- Nucleosome-remodeling factor subunit BPTF
- Nucleotide-binding oligomerization domain-containing protein 1, 2
- Oleandomycin glycosyltransferase
- Olfactory receptor 5K1
- Orexin receptor 1, 2
- Orphan nuclear receptor LRH-1
- P2X purinoceptor 4, 7
- p53-binding protein Mdm-2
- Paired box protein Pax-8
- Palmitoleoyl-protein carboxylesterase NOTUM
- Pancreatic alpha-amylase
- Pancreatic lipase
- Pantothenate kinase 3
- Parathyroid hormone receptor
- PAS domain-containing serine/threonine-protein kinase
- Patatin-like phospholipase domain-containing protein 2
- Peptide deformylase
- Peripheral-type benzodiazepine receptor
- Peroxisome proliferator-activated receptor Phenylethanolamine N-methyltransferase
- Phosphatidylcholine transfer protein
- Phosphatidylinositol kinase, PI4K, PI3K
- Phosphodiesterase 1-5, 7, 9-11
- Phosphoglycerate kinase
- Phospholipase
- Phosphotyrosine-protein phosphatase PTPB
- Photoreceptor-specific nuclear receptor
- Photosystem Q(B) protein
- Platelet activating factor receptor
- Platelet-derived growth factor receptor
- Poly [ADP-ribose] polymerase 1, 11, 12, 14
- Poly(ADP-ribose) glycohydrolase
- Potassium channel subfamily K, T
- Pregnane X receptor
- Prenyl protein specific protease
- Progesterone receptor
- Proline racemase
- Prostaglandin E synthase
- Prostanoid EP2/EP3 receptor
- Protein disulfide-isomerase
- Protein kinase C zeta, Pfmrk
- Protein tyrosine kinase 2 beta
- Protein-arginine N-methyltransferase 1
- Proteinase-activated receptor 1
- Protein-tyrosine phosphatase 2C, LC-PTP
- Pteridine reductase
- Purinergic receptor P2Y1
- Putative fructose-1,6-bisphosphate aldolase
- Putative hexokinase HKDC1
- Putative hydrolase RBBP9
- Pyruvate dehydrogenase kinase
- Quinolone resistance protein norA
- Quinone oxidoreductase
- Rap guanine nucleotide exchange factor 4
- Ras-related protein Rab-9A
- Receptor-interacting serine/threonine-protein kinase 1
- Regulator of G-protein signaling 12
- Regulatory protein RhlR
- Relaxin receptor 1
- Replicase polyprotein 1ab
- Replicative DNA helicase
- Retinoic acid receptor
- Rho-associated protein kinase 1, 2
- Ribosomal protein S6 kinase 1
- rRNA adenine N-6-methyltransferase
- Runt-related transcription factor 1/Core-binding factor subunit beta
- S-adenosylmethionine synthase isoform type-2
- SARS coronavirus 3C-like proteinase
- Sentrin-specific protease 1, 6, 7, 8
- Sepiapterin reductase
- Serine hydroxymethyltransferase, mitochondrial
- Serine protease hepsin
- Serine/threonine-protein kinase Serine/threonine-protein phosphatase
- Serotonin 1/2/3/6/7 receptor
- Serotonin N-acetyltransferase
- Short transient receptor potential channel 4
- Sialidase 3
- Signal transducer and activator of transcription 1, 3, 6
- Sodium channel protein type II alpha subunit
- Solute carrier organic anion transporter
- Sonic hedgehog protein
- Spermidine synthase
- Sphingosine 1-phosphate receptor Edg-1, Edg-5
- Sphingosine kinase 1
- STAM-binding protein
- Stem cell growth factor receptor
- Steroid 5-alpha-reductase 2
- Sterol 14-alpha demethylase
- Steryl-sulfatase
- Stimulator of interferon genes protein
- Streptokinase A
- Succinyl-diaminopimelate desuccinylase
- Sulfonylurea receptor 1, Kir6.2
- Sulfotransferase 1A1
- SUMO-activating enzyme
- Survival motor neuron protein
- Taq polymerase 1
- TAR DNA-binding protein 43
- Taste receptor type 2 member 14, 38, 39
- Testis-specific androgen-binding protein
- TGF-beta receptor type I
- Thioredoxin glutathione reductase
- Thymidine phosphorylase
- Thymidylate synthase
- Thyroid hormone receptor
- Toll-like receptor 2, 4, 7
- Trace amine-associated receptor 1
- Trans-cinnamate 4-monooxygenase
- Transcription factor SKN7
- Transcription intermediary factor 1-alpha
- Transcriptional activator protein lasR, luxR
- Transcriptional regulator MvfR
- Transient receptor potential cation channel Triosephosphate isomerase, glycosomal
- Tryptophan 2,3-dioxygenase
- Tumor necrosis factor receptor superfamily member 6
- Tumor susceptibility gene 101 protein
- Tumour suppressor p53/oncoprotein Mdm2
- Type-1 angiotensin II receptor
- Tyrosine-protein kinase
- Tyrosyl-DNA phosphodiesterase 1
- Ubiquitin carboxyl-terminal hydrolase 2, 8
- Ubiquitin-conjugating enzyme E2 N
- 1-carboxyvinyltransferase
- N-acetylglucosaminyltransferase 110 kDa subunit
- Urea transporter 1, 2
- Uridine phosphorylase 1
- Vanilloid receptor
- Vascular cell adhesion protein 1
- Vascular endothelial growth factor receptor 2
- Vasoactive intestinal polypeptide receptor 1
- Vasopressin V1b receptor
- Voltage-gated calcium channel
- Voltage-gated potassium channel subunit Kv7.2
- WD repeat-containing protein 5
- Werner syndrome ATP-dependent helicase
- X-box-binding protein 1
- Zinc finger protein GLI1, mex-5