Natural Product: NPC124784

Natural Product IDNPC124784
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Artocarpetin
IUPAC Name 2-(2,4-dihydroxyphenyl)-5-hydroxy-7-methoxychromen-4-one
Synonyms Artocarpetin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL460552
PubChem CID 12308618
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 VOCATNAJXJSCLN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O6/c1-21-9-5-12(19)16-13(20)7-14(22-15(16)6-9)10-3-2-8(17)4-11(10)18/h2-7,17-19H,1H3
SMILES COc1cc(O)c2c(c1)oc(cc2=O)c1ccc(cc1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.06 Volume:   291.273
?
Van der Waals volume.
Dense:   1.03 LogP:   2.495
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.456
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.152
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.672 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.42 Fsp3:   0.062
MCE-18:   18.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.604 Fluc inhibitor:   0.946
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.948
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.618
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.52 Promiscuous compounds:   0.905

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.995 MDCK Permeability:   -4.814
Pgp-inhibitor:   0.268 Pgp-substrate:   0.221
PAMPA:   0.099
?
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):   0.033
20% Bioavailability (F20%):   0.228 30% Bioavailability (F30%):   0.608
50% Bioavailability (F50%):   0.964

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.026 MRP1:   0.576
Plasma Protein Binding (PPB):   96.384% Volume Distribution (VD):   -0.21
Fu: 4.125%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.966
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.961
BSEP inhibitor:   0.647

ADMET: Metabolism

CYP1A2-inhibitor:   0.985 CYP1A2-substrate:   0.7
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.135
CYP2C9-inhibitor:   0.992 CYP2C9-substrate:   0.956
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.963
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.058
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.803
HLM stability:   0.761
?
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):  2.108 Half-life (T1/2):  1.63

ADMET: Toxicity

hERG Blockers:  0.084 hERG Blockers (10um):  0.51
Human Hepatotoxicity (H-HT):  0.418 Drug-induced Liver Injury (DILI):  0.759
AMES Toxicity:  0.65 Rat Oral Acute Toxicity:  0.475
Maximum Recommended Daily Dose:  0.817 Skin Sensitization:  0.528
Carcinogencity:  0.749 Eye Corrosion:  0.242
Eye Irritation:  0.995 Respiratory Toxicity:  0.845
Drug-induced Neurotoxicity:  0.061 Ototoxicity:  0.096
Hematotoxicity:  0.084 Drug-induced Nephrotoxicity:  0.06
Genotoxicity:  0.944 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.374 Hek293 Cytotoxicity:  0.76
BCF:   1.152
?
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:   3.765
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.219
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.692
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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
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. root n.a. DOI[10.1016/0031-9422(95)00135-T]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. root n.a. PMID[11395279]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota whole plants Shawnee National Forest, Harrisburg, IL, US n.a. PMID[11678652]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota whole plants n.a. n.a. PMID[11678652]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. PMID[12419367]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota leaves Kaohsiung, Taiwan 2006-SEP PMID[18986201]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota Fruits n.a. n.a. PMID[19296617]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota Wood n.a. n.a. PMID[23113717]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. formosan n.a. PMID[8864236]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. formosan n.a. PMID[8864236]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. PMID[9358644]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota Latex Exudate n.a. n.a. Database[FooDB]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. Database[FooDB]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. Database[FooDB]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17767 Artocarpus heterophyllus Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5495 Broussonetia papyrifera Species Moraceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 88.2 % PMID[8864236]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 85.7 % PMID[8864236]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 73.8 % PMID[8864236]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 0.0 % PMID[8864236]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 95900.0 nM PMID[8864236]

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 NPC124784 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
0.7593 Intermediate Similarity NPC234133
0.6842 Remote Similarity NPC108406
0.6786 Remote Similarity NPC127447
0.6786 Remote Similarity NPC29353
0.678 Remote Similarity NPC137062
0.6667 Remote Similarity NPC48479
0.661 Remote Similarity NPC223579
0.6545 Remote Similarity NPC274121
0.6441 Remote Similarity NPC328119
0.6379 Remote Similarity NPC33265
0.6333 Remote Similarity NPC195202
0.6232 Remote Similarity NPC194593
0.6176 Remote Similarity NPC603508
0.6066 Remote Similarity NPC177298
0.6027 Remote Similarity NPC55443
0.5972 Remote Similarity NPC265624
0.597 Remote Similarity NPC241100
0.597 Remote Similarity NPC59739
0.5857 Remote Similarity NPC600396
0.5833 Remote Similarity NPC205026
0.5833 Remote Similarity NPC143799
0.5833 Remote Similarity NPC146679
0.5775 Remote Similarity NPC159707
0.5714 Remote Similarity NPC67654
0.5714 Remote Similarity NPC90665
0.5694 Remote Similarity NPC121649
0.5667 Remote Similarity NPC16935
0.5645 Remote Similarity NPC200388
0.5634 Remote Similarity NPC158027
0.5616 Remote Similarity NPC18699
0.5574 Remote Similarity NPC198826
0.5556 Remote Similarity NPC14606
0.5556 Remote Similarity NPC55619
0.5352 Remote Similarity NPC248739
0.5333 Remote Similarity NPC213216
0.5323 Remote Similarity NPC231772
0.5323 Remote Similarity NPC87125
0.5323 Remote Similarity NPC188871
0.5323 Remote Similarity NPC120163
0.5238 Remote Similarity NPC222830
0.5238 Remote Similarity NPC78913
0.5231 Remote Similarity NPC183950
0.5231 Remote Similarity NPC252933
0.5231 Remote Similarity NPC78326
0.5172 Remote Similarity NPC31872
0.5161 Remote Similarity NPC103904
0.5161 Remote Similarity NPC262094
0.5161 Remote Similarity NPC152042
0.5156 Remote Similarity NPC230943
0.5156 Remote Similarity NPC200740
0.5156 Remote Similarity NPC270620
0.5156 Remote Similarity NPC246204
0.5147 Remote Similarity NPC55018
0.5147 Remote Similarity NPC602829
0.5135 Remote Similarity NPC331652
0.5079 Remote Similarity NPC57030
0.5079 Remote Similarity NPC250266
0.5079 Remote Similarity NPC120464
0.5079 Remote Similarity NPC483773
0.5077 Remote Similarity NPC58382
0.5077 Remote Similarity NPC52005
0.5068 Remote Similarity NPC600972
0.5068 Remote Similarity NPC601984
0.5067 Remote Similarity NPC39360
0.5067 Remote Similarity NPC29763
0.5067 Remote Similarity NPC210003
0.5065 Remote Similarity NPC27942

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC124784 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
NPD

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