Natural Product: NPC170492

Natural Product IDNPC170492
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Artochamin C
IUPAC Name 2-(3,4-dihydroxyphenyl)-5-hydroxy-8,8-dimethylpyrano[2,3-h]chromen-4-one
Synonyms Artochamin C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL445760
PubChem CID 10247422
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0003520] Pyranoflavonoids

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 QNSVTPUDNHNRQZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H16O6/c1-20(2)6-5-11-17(26-20)9-15(24)18-14(23)8-16(25-19(11)18)10-3-4-12(21)13(22)7-10/h3-9,21-22,24H,1-2H3
SMILES Oc1ccc(cc1O)c1cc(=O)c2c(o1)c1C=CC(Oc1cc2O)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   352.09 Volume:   349.264
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Van der Waals volume.
Dense:   1.008 LogP:   3.344
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.745
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.108
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   100.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.577 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.946 Fsp3:   0.15
MCE-18:   52.174
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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:   1
Colloidal aggregators:   0.757 Fluc inhibitor:   0.689
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.98
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.834
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.407 Promiscuous compounds:   0.325

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.961 MDCK Permeability:   -4.716
Pgp-inhibitor:   0.211 Pgp-substrate:   0.018
PAMPA:   0.257
?
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):   0.007
20% Bioavailability (F20%):   0.99 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.068 MRP1:   0.941
Plasma Protein Binding (PPB):   98.181% Volume Distribution (VD):   -0.127
Fu: 1.679%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.979 BCRP inhibitor:   0.946
BSEP inhibitor:   0.978

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.115
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.316 CYP2C9-substrate:   0.016
CYP2D6-inhibitor:   0.093 CYP2D6-substrate:   0.881
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.991
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.575
HLM stability:   0.879
?
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):  9.155 Half-life (T1/2):  1.347

ADMET: Toxicity

hERG Blockers:  0.067 hERG Blockers (10um):  0.565
Human Hepatotoxicity (H-HT):  0.395 Drug-induced Liver Injury (DILI):  0.921
AMES Toxicity:  0.71 Rat Oral Acute Toxicity:  0.564
Maximum Recommended Daily Dose:  0.772 Skin Sensitization:  0.935
Carcinogencity:  0.761 Eye Corrosion:  0.098
Eye Irritation:  0.987 Respiratory Toxicity:  0.767
Drug-induced Neurotoxicity:  0.015 Ototoxicity:  0.22
Hematotoxicity:  0.071 Drug-induced Nephrotoxicity:  0.036
Genotoxicity:  0.949 RPMI-8226 Immunitoxicity:  0.043
A549 Cytotoxicity:  0.5 Hek293 Cytotoxicity:  0.515
BCF:   1.63
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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:   4.439
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.768
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.234
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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
NPO28803 Artocarpus chama Species Moraceae Eukaryota n.a. root n.a. PMID[15165133]
NPO28969 Solanum sarrachoides Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29358 Senecio oxyodon Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29519 Primula glaucescens Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29409 Oenothera laciniata Species Onagraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29462 Helinus ovatus Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29156 Conyza incana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29318 Cereus validus Species Cactaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28803 Artocarpus chama Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29386 Agabus bipustulatus Species Dytiscidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28969 Solanum sarrachoides Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28969 Solanum sarrachoides Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28969 Solanum sarrachoides Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29318 Cereus validus Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29156 Conyza incana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29409 Oenothera laciniata Species Onagraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29358 Senecio oxyodon Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28803 Artocarpus chama Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29462 Helinus ovatus Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29519 Primula glaucescens Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28969 Solanum sarrachoides Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29386 Agabus bipustulatus Species Dytiscidae 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
NPT81 Cell line A549 Homo sapiens ED50 = 3.0 ug ml-1 PMID[15165133]
NPT83 Cell line MCF7 Homo sapiens ED50 = 2.2 ug ml-1 PMID[15165133]
NPT309 Cell line 1A9 Homo sapiens ED50 = 2.0 ug ml-1 PMID[15165133]
NPT180 Cell line HCT-8 Homo sapiens ED50 = 2.3 ug ml-1 PMID[15165133]
NPT308 Cell line CAKI-1 Homo sapiens ED50 = 5.3 ug ml-1 PMID[15165133]
NPT147 Cell line SK-MEL-2 Homo sapiens ED50 = 2.3 ug ml-1 PMID[15165133]
NPT306 Cell line PC-3 Homo sapiens ED50 = 4.2 ug ml-1 PMID[15165133]
NPT82 Cell line MDA-MB-231 Homo sapiens ED50 = 6.2 ug ml-1 PMID[15165133]
NPT91 Cell line KB Homo sapiens ED50 = 3.4 ug ml-1 PMID[15165133]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 7.2 ug ml-1 PMID[15165133]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 3.4 ug ml-1 PMID[15165133]

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 NPC170492 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
0.8525 High Similarity NPC293852
0.6522 Remote Similarity NPC166757
0.5797 Remote Similarity NPC242100
0.5775 Remote Similarity NPC211811
0.5694 Remote Similarity NPC275122
0.5556 Remote Similarity NPC24673
0.5556 Remote Similarity NPC265932
0.55 Remote Similarity NPC276444
0.5467 Remote Similarity NPC471984
0.5429 Remote Similarity NPC157855
0.5417 Remote Similarity NPC17848
0.5333 Remote Similarity NPC57393
0.5309 Remote Similarity NPC189087
0.5309 Remote Similarity NPC62840
0.5309 Remote Similarity NPC603859
0.5294 Remote Similarity NPC108406
0.527 Remote Similarity NPC55662
0.527 Remote Similarity NPC120105
0.527 Remote Similarity NPC5322
0.5238 Remote Similarity NPC198829
0.5211 Remote Similarity NPC88804
0.5205 Remote Similarity NPC259456
0.5195 Remote Similarity NPC486091
0.5195 Remote Similarity NPC15435
0.5181 Remote Similarity NPC217083
0.5181 Remote Similarity NPC478514
0.5128 Remote Similarity NPC214236
0.5062 Remote Similarity NPC482611

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC170492 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