Natural Product: NPC28274

Natural Product IDNPC28274
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Syringetin
IUPAC Name 3,5,7-trihydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)chromen-4-one
Synonyms Syringetin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL489142
PubChem CID 5281953
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001136] Flavonols

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey UZMAPBJVXOGOFT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O8/c1-23-11-3-7(4-12(24-2)14(11)20)17-16(22)15(21)13-9(19)5-8(18)6-10(13)25-17/h3-6,18-20,22H,1-2H3
SMILES COc1cc(cc(c1O)OC)c1oc2cc(O)cc(c2c(=O)c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.07 Volume:   326.149
?
Van der Waals volume.
Dense:   1.061 LogP:   1.629
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.808
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.909
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   129.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.568 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.541 Fsp3:   0.118
MCE-18:   20.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.768 Fluc inhibitor:   0.335
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.874
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.64
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.467 Promiscuous compounds:   0.921

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.486 MDCK Permeability:   -4.873
Pgp-inhibitor:   0.97 Pgp-substrate:   0.083
PAMPA:   0.034
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.268
20% Bioavailability (F20%):   0.009 30% Bioavailability (F30%):   0.507
50% Bioavailability (F50%):   0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.782
Plasma Protein Binding (PPB):   98.296% Volume Distribution (VD):   -0.689
Fu: 1.163%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.926

ADMET: Metabolism

CYP1A2-inhibitor:   0.852 CYP1A2-substrate:   0.863
CYP2C19-inhibitor:   0.017 CYP2C19-substrate:   0.959
CYP2C9-inhibitor:   0.34 CYP2C9-substrate:   0.06
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.854
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.996
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  4.072 Half-life (T1/2):  1.674

ADMET: Toxicity

hERG Blockers:  0.054 hERG Blockers (10um):  0.443
Human Hepatotoxicity (H-HT):  0.402 Drug-induced Liver Injury (DILI):  0.713
AMES Toxicity:  0.493 Rat Oral Acute Toxicity:  0.485
Maximum Recommended Daily Dose:  0.711 Skin Sensitization:  0.526
Carcinogencity:  0.718 Eye Corrosion:  0.463
Eye Irritation:  0.995 Respiratory Toxicity:  0.779
Drug-induced Neurotoxicity:  0.053 Ototoxicity:  0.111
Hematotoxicity:  0.122 Drug-induced Nephrotoxicity:  0.046
Genotoxicity:  0.828 RPMI-8226 Immunitoxicity:  0.085
A549 Cytotoxicity:  0.259 Hek293 Cytotoxicity:  0.597
BCF:   0.979
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.608
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.347
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.8
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. leaf n.a. DOI[10.1016/S0031-9422(01)00320-X]
NPO21179 Streptomyces griseoaurantiacus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[10048567]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. leaf n.a. PMID[11738417]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. PMID[19919095]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. fruit n.a. PMID[21462031]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota flower buds and leaves Khon Kaen province, Thailand 2010 PMID[23270663]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Leaves n.a. n.a. PMID[23642481]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Flowers n.a. n.a. PMID[26462418]
NPO21179 Streptomyces griseoaurantiacus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13308 Polycitor adriaticus Species Polycitoridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18881 Loropetalum chinense Species Hamamelidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14307 Rhizopus oryzae Species Rhizopodaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22530 Vigna luteola Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18881 Loropetalum chinense Species Hamamelidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14307 Rhizopus oryzae Species Rhizopodaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18881 Loropetalum chinense Species Hamamelidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18881 Loropetalum chinense Species Hamamelidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23194 Berberis beaniana Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18881 Loropetalum chinense Species Hamamelidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22147 Goniothalamus macrophyllus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21894 Psychotria granadensis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22968 Elaeocarpus serratus Species Elaeocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15469 Myodocarpus gracilis Species Myodocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6953.1 Aconitum sachalinense subsp. yezoense Subspecies Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20425 Epimedium macranthum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26293 Ginkgo biloba Species Ginkgoaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21704 Papaver suaveolens Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23157 Wigandia kunthii Species Namaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14307 Rhizopus oryzae Species Rhizopodaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13308 Polycitor adriaticus Species Polycitoridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21179 Streptomyces griseoaurantiacus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO22530 Vigna luteola Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT13 Individual protein Tyrosine-protein kinase LCK Homo sapiens IC50 = 20.0 ug.mL-1 PMID[1479375]
NPT1443 Individual protein Pyruvate dehydrogenase kinase isoform 1 Homo sapiens Inhibition = 14.98 % PMID[28049590]
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens FC = 1.9 n.a. PMID[19807106]
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens FC = 1.2 n.a. PMID[19807106]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT191 Organism Hepatitis C virus Hepatitis C virus EC50 = 15500.0 nM PMID[22445328]
NPT2 Others Unspecified n.a. IC50 = 24.0 ug.mL-1 PMID[1800636]
NPT2 Others Unspecified n.a. IC50 = 2100.0 nM PMID[8882428]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC28274 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.82 Intermediate Similarity NPC219330
0.7778 Intermediate Similarity NPC133953
0.7778 Intermediate Similarity NPC125062
0.7407 Intermediate Similarity NPC54394
0.7407 Intermediate Similarity NPC159103
0.7358 Intermediate Similarity NPC50403
0.7358 Intermediate Similarity NPC241838
0.7273 Intermediate Similarity NPC609179
0.7037 Intermediate Similarity NPC120464
0.6604 Remote Similarity NPC179271
0.6538 Remote Similarity NPC116775
0.6538 Remote Similarity NPC187432
0.6441 Remote Similarity NPC483775
0.6415 Remote Similarity NPC169749
0.6415 Remote Similarity NPC20791
0.5862 Remote Similarity NPC62536
0.5862 Remote Similarity NPC610359
0.5833 Remote Similarity NPC606638
0.5818 Remote Similarity NPC601197
0.5738 Remote Similarity NPC183950
0.5738 Remote Similarity NPC252933
0.5738 Remote Similarity NPC279989
0.5714 Remote Similarity NPC216361
0.5614 Remote Similarity NPC256042
0.5593 Remote Similarity NPC143799
0.5593 Remote Similarity NPC483773
0.5574 Remote Similarity NPC162351
0.5574 Remote Similarity NPC12200
0.5574 Remote Similarity NPC603596
0.5574 Remote Similarity NPC610401
0.5424 Remote Similarity NPC123886
0.5424 Remote Similarity NPC184536
0.5424 Remote Similarity NPC103342
0.5424 Remote Similarity NPC152042
0.541 Remote Similarity NPC200740
0.541 Remote Similarity NPC82325
0.541 Remote Similarity NPC166753
0.5385 Remote Similarity NPC205046
0.5333 Remote Similarity NPC286342
0.5333 Remote Similarity NPC59951
0.5333 Remote Similarity NPC231772
0.5333 Remote Similarity NPC87125
0.5333 Remote Similarity NPC197285
0.5333 Remote Similarity NPC601901
0.5333 Remote Similarity NPC605755
0.5323 Remote Similarity NPC52005
0.5323 Remote Similarity NPC602125
0.5303 Remote Similarity NPC200694
0.5286 Remote Similarity NPC171821
0.5278 Remote Similarity NPC254306
0.5263 Remote Similarity NPC606270
0.5254 Remote Similarity NPC26227
0.5246 Remote Similarity NPC600900
0.5238 Remote Similarity NPC604021
0.5167 Remote Similarity NPC284552
0.5167 Remote Similarity NPC44079
0.5167 Remote Similarity NPC98661
0.5156 Remote Similarity NPC227192
0.5082 Remote Similarity NPC201451
0.5082 Remote Similarity NPC48479
0.5067 Remote Similarity NPC21100
0.5067 Remote Similarity NPC325555
0.5067 Remote Similarity NPC226304

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC28274 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.6415 Remote Similarity NPD1512 Phase 3

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data