Natural Product: NPC200388

Natural Product IDNPC200388
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Oxyayanin A
IUPAC Name 2-(2,5-dihydroxy-4-methoxyphenyl)-5-hydroxy-3,7-dimethoxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL491989
PubChem CID 5281676
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 KGJTXYKKHKRNIM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O8/c1-23-8-4-12(21)15-14(5-8)26-17(18(25-3)16(15)22)9-6-11(20)13(24-2)7-10(9)19/h4-7,19-21H,1-3H3
SMILES COc1cc(c2c(c1)oc(c1cc(c(cc1O)OC)O)c(c2=O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.08 Volume:   343.445
?
Van der Waals volume.
Dense:   1.048 LogP:   2.259
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.309
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.279
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   118.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.608 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.582 Fsp3:   0.167
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:   0.378 Fluc inhibitor:   0.34
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.834
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.644
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.39 Promiscuous compounds:   0.81

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.181 MDCK Permeability:   -4.787
Pgp-inhibitor:   0.94 Pgp-substrate:   0.269
PAMPA:   0.066
?
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):   0.07
20% Bioavailability (F20%):   0.019 30% Bioavailability (F30%):   0.175
50% Bioavailability (F50%):   0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.788
Plasma Protein Binding (PPB):   96.43% Volume Distribution (VD):   -0.549
Fu: 3.479%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.834
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.976
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   0.987 CYP1A2-substrate:   0.822
CYP2C19-inhibitor:   0.379 CYP2C19-substrate:   0.156
CYP2C9-inhibitor:   0.981 CYP2C9-substrate:   0.491
CYP2D6-inhibitor:   0.994 CYP2D6-substrate:   0.83
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.938
HLM stability:   0.935
?
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):  7.328 Half-life (T1/2):  1.549

ADMET: Toxicity

hERG Blockers:  0.057 hERG Blockers (10um):  0.478
Human Hepatotoxicity (H-HT):  0.385 Drug-induced Liver Injury (DILI):  0.746
AMES Toxicity:  0.561 Rat Oral Acute Toxicity:  0.422
Maximum Recommended Daily Dose:  0.603 Skin Sensitization:  0.593
Carcinogencity:  0.703 Eye Corrosion:  0.374
Eye Irritation:  0.988 Respiratory Toxicity:  0.826
Drug-induced Neurotoxicity:  0.048 Ototoxicity:  0.117
Hematotoxicity:  0.163 Drug-induced Nephrotoxicity:  0.091
Genotoxicity:  0.608 RPMI-8226 Immunitoxicity:  0.114
A549 Cytotoxicity:  0.307 Hek293 Cytotoxicity:  0.473
BCF:   1.042
?
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:   3.641
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.397
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.752
?
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
NPO22842 Lissoclinum bistratum Species Didemnidae Eukaryota n.a. n.a. n.a. PMID[12608858]
NPO23263 Crinum yemense Species Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[15270564]
NPO23510 Vicia faba Species Fabaceae Eukaryota flowers n.a. n.a. PMID[16180811]
NPO23510 Vicia faba Species Fabaceae Eukaryota n.a. leaf n.a. PMID[22014228]
NPO23510 Vicia faba Species Fabaceae Eukaryota n.a. branch n.a. PMID[22014228]
NPO23510 Vicia faba Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22014228]
NPO17909 Berberis vulgaris Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[30701972]
NPO17909 Berberis vulgaris Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[38731544]
NPO23510 Vicia faba Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[39355945]
NPO22842 Lissoclinum bistratum Species Didemnidae Eukaryota n.a. n.a. n.a. PMID[7807120]
NPO18832 Berberis thunbergii Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO547 Thalictrum lucidum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23562 Pachyphragma macrophyllum Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23107 Adiantum monochlamys Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23263 Crinum yemense Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11640 Berberis fortunei Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22186 Baileya pauciradiata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17909 Berberis vulgaris Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22842 Lissoclinum bistratum Species Didemnidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18884 Apuleia leiocarpa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23427 Becium grandiflorum n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO23510 Vicia faba Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23510 Vicia faba Species Fabaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO23510 Vicia faba Species Fabaceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO23510 Vicia faba Species Fabaceae Eukaryota Oil n.a. n.a. Database[FooDB]
NPO23510 Vicia faba Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO23510 Vicia faba Species Fabaceae Eukaryota Sprout Seedling n.a. n.a. Database[FooDB]
NPO23510 Vicia faba Species Fabaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO23510 Vicia faba Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO18832 Berberis thunbergii Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22186 Baileya pauciradiata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17909 Berberis vulgaris Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23510 Vicia faba Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1473 Xanthorhiza simplicissima Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18295 Berberis amurensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO547 Thalictrum lucidum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31574 Mahonia fortunei n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18295 Berberis amurensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22186 Baileya pauciradiata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO547 Thalictrum lucidum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23107 Adiantum monochlamys Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11640 Berberis fortunei Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17909 Berberis vulgaris Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1473 Xanthorhiza simplicissima Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18832 Berberis thunbergii Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23510 Vicia faba Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18832 Berberis thunbergii Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23510 Vicia faba Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO547 Thalictrum lucidum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22186 Baileya pauciradiata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31574 Mahonia fortunei n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17909 Berberis vulgaris Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18295 Berberis amurensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1473 Xanthorhiza simplicissima Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11640 Berberis fortunei Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6943 Vernonanthura chamaedrys Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22186 Baileya pauciradiata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20857 Commiphora erythraea Species Burseraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23107 Adiantum monochlamys Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13731 Centaurea webbiana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23562 Pachyphragma macrophyllum Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1473 Xanthorhiza simplicissima Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23263 Crinum yemense Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23510 Vicia faba Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23648 Spilanthes mauritiana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23427 Becium grandiflorum n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22842 Lissoclinum bistratum Species Didemnidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18295 Berberis amurensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17909 Berberis vulgaris Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18832 Berberis thunbergii Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO547 Thalictrum lucidum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11640 Berberis fortunei Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18884 Apuleia leiocarpa Species Fabaceae 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
NPT91 Cell line KB Homo sapiens ED50 = 1.99 ug ml-1 PMID[1955888]

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 NPC200388 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
0.7636 Intermediate Similarity NPC55619
0.7455 Intermediate Similarity NPC246204
0.7273 Intermediate Similarity NPC100916
0.6842 Remote Similarity NPC270620
0.661 Remote Similarity NPC78326
0.6607 Remote Similarity NPC103904
0.6607 Remote Similarity NPC262094
0.6491 Remote Similarity NPC76376
0.6491 Remote Similarity NPC146679
0.6491 Remote Similarity NPC188871
0.6441 Remote Similarity NPC58382
0.6441 Remote Similarity NPC206604
0.6167 Remote Similarity NPC236769
0.5806 Remote Similarity NPC193842
0.5692 Remote Similarity NPC99671
0.5645 Remote Similarity NPC124784
0.5484 Remote Similarity NPC200740
0.5484 Remote Similarity NPC604677
0.5397 Remote Similarity NPC223579
0.5238 Remote Similarity NPC153758
0.5238 Remote Similarity NPC328119
0.5161 Remote Similarity NPC48479
0.5161 Remote Similarity NPC87125
0.5161 Remote Similarity NPC605755
0.5156 Remote Similarity NPC177298
0.5079 Remote Similarity NPC108406
0.5077 Remote Similarity NPC252933
0.5077 Remote Similarity NPC137062

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC200388 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