Natural Product: NPC56031

Natural Product IDNPC56031
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1-(2,4-Dihydroxy-6-Methoxyphenyl)-3-(4-Methoxyphenyl)Prop-2-En-1-One
IUPAC Name (E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL494264
PubChem CID 11449431
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003472] 2'-Hydroxychalcones

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 YROJPKUFDFWHAO-VMPITWQZSA-N
Standard InCHI InChI=1S/C17H16O5/c1-21-13-6-3-11(4-7-13)5-8-14(19)17-15(20)9-12(18)10-16(17)22-2/h3-10,18,20H,1-2H3/b8-5+
SMILES COc1ccc(cc1)/C=C/C(=O)c1c(cc(cc1OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   308.335
?
Van der Waals volume.
Dense:   0.973 LogP:   2.944
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.128
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.838
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.655 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.125 Fsp3:   0.118
MCE-18:   13.0
?
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:   0.81 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.372
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.835
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.65 Promiscuous compounds:   0.668

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.048 MDCK Permeability:   -4.859
Pgp-inhibitor:   0.942 Pgp-substrate:   0.001
PAMPA:   0.009
?
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):   0.011
20% Bioavailability (F20%):   0.739 30% Bioavailability (F30%):   0.926
50% Bioavailability (F50%):   0.965

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.0
Plasma Protein Binding (PPB):   97.672% Volume Distribution (VD):   -0.026
Fu: 1.888%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.991
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.037 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.996
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.178
?
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):  9.3 Half-life (T1/2):  0.747

ADMET: Toxicity

hERG Blockers:  0.244 hERG Blockers (10um):  0.506
Human Hepatotoxicity (H-HT):  0.564 Drug-induced Liver Injury (DILI):  0.545
AMES Toxicity:  0.529 Rat Oral Acute Toxicity:  0.158
Maximum Recommended Daily Dose:  0.618 Skin Sensitization:  0.653
Carcinogencity:  0.399 Eye Corrosion:  0.103
Eye Irritation:  0.989 Respiratory Toxicity:  0.777
Drug-induced Neurotoxicity:  0.531 Ototoxicity:  0.179
Hematotoxicity:  0.188 Drug-induced Nephrotoxicity:  0.334
Genotoxicity:  0.374 RPMI-8226 Immunitoxicity:  0.104
A549 Cytotoxicity:  0.2 Hek293 Cytotoxicity:  0.611
BCF:   1.614
?
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:   4.211
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.737
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.122
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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
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO583 Goniothalamus gardneri Species Annonaceae 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
NPT111 Cell line K562 Homo sapiens GI50 = 17000.0 nM PMID[18798609]
NPT306 Cell line PC-3 Homo sapiens GI50 = 19300.0 nM PMID[18798609]
NPT139 Cell line HT-29 Homo sapiens GI50 = 21600.0 nM PMID[18798609]
NPT387 Cell line M14 Homo sapiens GI50 = 19600.0 nM PMID[18798609]
NPT83 Cell line MCF7 Homo sapiens GI50 = 17300.0 nM PMID[18798609]
NPT90 Cell line DU-145 Homo sapiens GI50 = 9000.0 nM PMID[18798609]
NPT397 Cell line NCI-H460 Homo sapiens GI50 = 14000.0 nM PMID[18798609]
NPT886 Cell line NIH3T3 Mus musculus GI50 = 6700.0 nM PMID[18798609]
NPT165 Cell line HeLa Homo sapiens IC50 = 47700.0 nM PMID[25629304]
NPT81 Cell line A549 Homo sapiens IC50 > 50000.0 nM PMID[25629304]
NPT65 Cell line HepG2 Homo sapiens IC50 = 18100.0 nM PMID[25629304]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 > 25000.0 nM PMID[18798609]
NPT1596 Organism Leishmania peruviana Leishmania peruviana IC50 = 23000.0 nM PMID[19962891]
NPT1208 Organism Leishmania braziliensis Leishmania braziliensis IC50 = 7600.0 nM PMID[19962891]
NPT634 Organism Leishmania amazonensis Leishmania amazonensis IC50 = 10000.0 nM PMID[19962891]
NPT634 Organism Leishmania amazonensis Leishmania amazonensis IC50 = 14300.0 nM PMID[19962891]
NPT2 Others Unspecified n.a. Ratio IC50 = 16.6 n.a. PMID[19962891]

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 NPC56031 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
0.8222 Intermediate Similarity NPC87231
0.8222 Intermediate Similarity NPC129132
0.7391 Intermediate Similarity NPC242294
0.6875 Remote Similarity NPC265045
0.6667 Remote Similarity NPC262359
0.64 Remote Similarity NPC263670
0.6383 Remote Similarity NPC139813
0.62 Remote Similarity NPC188646
0.6182 Remote Similarity NPC25287
0.6 Remote Similarity NPC482939
0.5882 Remote Similarity NPC605344
0.5849 Remote Similarity NPC472365
0.5818 Remote Similarity NPC91236
0.5818 Remote Similarity NPC99333
0.5769 Remote Similarity NPC119660
0.5769 Remote Similarity NPC93034
0.5741 Remote Similarity NPC472364
0.5714 Remote Similarity NPC212631
0.5714 Remote Similarity NPC608685
0.5686 Remote Similarity NPC205468
0.566 Remote Similarity NPC471417
0.566 Remote Similarity NPC150399
0.56 Remote Similarity NPC192304
0.5556 Remote Similarity NPC473391
0.549 Remote Similarity NPC257756
0.549 Remote Similarity NPC64359
0.5472 Remote Similarity NPC20560
0.5417 Remote Similarity NPC45438
0.5417 Remote Similarity NPC73532
0.5417 Remote Similarity NPC211120
0.5345 Remote Similarity NPC317119
0.5345 Remote Similarity NPC284080
0.5345 Remote Similarity NPC606423
0.5333 Remote Similarity NPC21350
0.5319 Remote Similarity NPC212379
0.5306 Remote Similarity NPC176930
0.5306 Remote Similarity NPC485640
0.5306 Remote Similarity NPC602047
0.5283 Remote Similarity NPC312318
0.5283 Remote Similarity NPC308037
0.5283 Remote Similarity NPC477243
0.5273 Remote Similarity NPC287789
0.5254 Remote Similarity NPC249606
0.5192 Remote Similarity NPC336114
0.5091 Remote Similarity NPC102003
0.5091 Remote Similarity NPC476333
0.5091 Remote Similarity NPC175098
0.5091 Remote Similarity NPC337373
0.5091 Remote Similarity NPC472366
0.5091 Remote Similarity NPC144281
0.5085 Remote Similarity NPC477244
0.5075 Remote Similarity NPC88484

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC56031 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