Natural Product: NPC181209

Natural Product IDNPC181209
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Odoratin
IUPAC Name 7-hydroxy-3-(3-hydroxy-4-methoxyphenyl)-6-methoxychromen-4-one
Synonyms Odoratin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL469824
PubChem CID 13965473
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids
            • [CHEMONTID:0003651] 3'-hydroxy,4'-methoxyisoflavonoids

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 BYNYZQQDQIQLSO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O6/c1-21-14-4-3-9(5-12(14)18)11-8-23-15-7-13(19)16(22-2)6-10(15)17(11)20/h3-8,18-19H,1-2H3
SMILES COc1ccc(cc1O)c1coc2cc(c(cc2c1=O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.08 Volume:   308.569
?
Van der Waals volume.
Dense:   1.018 LogP:   1.457
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.675
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.646
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.772 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.262 Fsp3:   0.118
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.442 Fluc inhibitor:   0.926
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.98
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.631
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.451 Promiscuous compounds:   0.63

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.062 MDCK Permeability:   -4.765
Pgp-inhibitor:   0.182 Pgp-substrate:   0.18
PAMPA:   0.086
?
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):   0.165
20% Bioavailability (F20%):   0.406 30% Bioavailability (F30%):   0.663
50% Bioavailability (F50%):   0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.714
Plasma Protein Binding (PPB):   90.869% Volume Distribution (VD):   -0.537
Fu: 9.987%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.967
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.959
BSEP inhibitor:   0.535

ADMET: Metabolism

CYP1A2-inhibitor:   0.902 CYP1A2-substrate:   0.948
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.118
CYP2C9-inhibitor:   0.887 CYP2C9-substrate:   0.394
CYP2D6-inhibitor:   0.837 CYP2D6-substrate:   0.019
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.318
CYP2B6-substrate:   0.004 CYP2C8-inhibitor:   0.999
HLM stability:   0.376
?
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):  2.824 Half-life (T1/2):  1.97

ADMET: Toxicity

hERG Blockers:  0.166 hERG Blockers (10um):  0.561
Human Hepatotoxicity (H-HT):  0.5 Drug-induced Liver Injury (DILI):  0.739
AMES Toxicity:  0.599 Rat Oral Acute Toxicity:  0.525
Maximum Recommended Daily Dose:  0.737 Skin Sensitization:  0.368
Carcinogencity:  0.768 Eye Corrosion:  0.058
Eye Irritation:  0.971 Respiratory Toxicity:  0.8
Drug-induced Neurotoxicity:  0.334 Ototoxicity:  0.26
Hematotoxicity:  0.227 Drug-induced Nephrotoxicity:  0.313
Genotoxicity:  0.54 RPMI-8226 Immunitoxicity:  0.151
A549 Cytotoxicity:  0.274 Hek293 Cytotoxicity:  0.458
BCF:   0.865
?
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:   3.492
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.232
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.781
?
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
NPO15117 Chromolaena odorata Species Asteraceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)88710-5]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. root n.a. DOI[10.1021/np50075a009]
NPO20635 Dalbergia frutescens Species Fabaceae Eukaryota bark n.a. n.a. PMID[11076565]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. root n.a. PMID[15763368]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. root n.a. PMID[17253088]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22209460]
NPO15117 Chromolaena odorata Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23186307]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25068786]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25844502]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[30758201]
NPO20635 Dalbergia frutescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15117 Chromolaena odorata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO277 Caulis millettiae n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5195.1 Odontites vernus subsp. serotinus Subspecies Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29789 Odontites serotina Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29789 Odontites serotina Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO277 Caulis millettiae n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO5195.1 Odontites vernus subsp. serotinus Subspecies Orobanchaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15117 Chromolaena odorata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5195.1 Odontites vernus subsp. serotinus Subspecies Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20635 Dalbergia frutescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28914 Caragana sinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15117 Chromolaena odorata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15715 Astragalus mongholicus 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 70000.0 nM PMID[24047800]
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens EC50 = 3100.0 nM PMID[23186307]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT848 Cell line N9 Homo sapiens IC50 = 11210.0 nM PMID[28073678]
NPT34 Cell line BV-2 Mus musculus IC50 = 18460.0 nM PMID[28911817]

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 NPC181209 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
0.8269 Intermediate Similarity NPC121522
0.7593 Intermediate Similarity NPC100971
0.75 Intermediate Similarity NPC80710
0.7288 Intermediate Similarity NPC260640
0.7193 Intermediate Similarity NPC487216
0.7143 Intermediate Similarity NPC209487
0.7069 Intermediate Similarity NPC134726
0.6897 Remote Similarity NPC100263
0.6724 Remote Similarity NPC264289
0.661 Remote Similarity NPC194653
0.6441 Remote Similarity NPC139293
0.6207 Remote Similarity NPC603503
0.5932 Remote Similarity NPC10467
0.5833 Remote Similarity NPC209560
0.5833 Remote Similarity NPC490700
0.5667 Remote Similarity NPC35763
0.5645 Remote Similarity NPC12377
0.5574 Remote Similarity NPC245382
0.5574 Remote Similarity NPC124714
0.5556 Remote Similarity NPC139364
0.5517 Remote Similarity NPC120924
0.55 Remote Similarity NPC605229
0.5493 Remote Similarity NPC184755
0.5424 Remote Similarity NPC195919
0.5395 Remote Similarity NPC229729
0.5323 Remote Similarity NPC181124
0.5323 Remote Similarity NPC69430
0.5323 Remote Similarity NPC203747
0.5312 Remote Similarity NPC195763
0.5254 Remote Similarity NPC182428
0.5238 Remote Similarity NPC250557
0.5238 Remote Similarity NPC487217
0.5231 Remote Similarity NPC200060
0.5161 Remote Similarity NPC116632
0.5161 Remote Similarity NPC474340
0.5161 Remote Similarity NPC333691
0.5161 Remote Similarity NPC269451
0.5079 Remote Similarity NPC186507
0.5079 Remote Similarity NPC294409
0.5079 Remote Similarity NPC490701
0.5079 Remote Similarity NPC609386
0.5079 Remote Similarity NPC610981
0.5077 Remote Similarity NPC191741
0.507 Remote Similarity NPC604255
0.5065 Remote Similarity NPC488441
0.5063 Remote Similarity NPC243877

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC181209 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