Natural Product: NPC277394

Natural Product IDNPC277394
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (4E,6E)-7-(3,4-Dihydroxyphenyl)-1-(4-Hydroxyphenyl)Hepta-4,6-Dien-3-One
IUPAC Name (4E,6E)-7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)hepta-4,6-dien-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2398587
PubChem CID 72164688
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids

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 UWTOEMORWLXHJO-ZPUQHVIOSA-N
Standard InCHI InChI=1S/C19H18O4/c20-16(9-5-14-6-10-17(21)11-7-14)4-2-1-3-15-8-12-18(22)19(23)13-15/h1-4,6-8,10-13,21-23H,5,9H2/b3-1+,4-2+
SMILES C(=Cc1ccc(c(c1)O)O)/C=C/C(=O)CCc1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   310.12 Volume:   331.5
?
Van der Waals volume.
Dense:   0.936 LogP:   2.432
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.43
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.367
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   15.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.433 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.42 Fsp3:   0.105
MCE-18:   12.0
?
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:   1
Colloidal aggregators:   0.98 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.134
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.687
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.82 Promiscuous compounds:   0.241

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.914 MDCK Permeability:   -4.812
Pgp-inhibitor:   0.074 Pgp-substrate:   0.004
PAMPA:   0.546
?
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):   0.0
20% Bioavailability (F20%):   0.898 30% Bioavailability (F30%):   0.961
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.029
Plasma Protein Binding (PPB):   94.555% Volume Distribution (VD):   -0.562
Fu: 5.316%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.008
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.007
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.044
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.01
CYP2D6-inhibitor:   0.994 CYP2D6-substrate:   0.972
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.978
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.678
?
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):  14.835 Half-life (T1/2):  1.233

ADMET: Toxicity

hERG Blockers:  0.463 hERG Blockers (10um):  0.792
Human Hepatotoxicity (H-HT):  0.599 Drug-induced Liver Injury (DILI):  0.124
AMES Toxicity:  0.665 Rat Oral Acute Toxicity:  0.202
Maximum Recommended Daily Dose:  0.749 Skin Sensitization:  0.999
Carcinogencity:  0.218 Eye Corrosion:  0.017
Eye Irritation:  0.952 Respiratory Toxicity:  0.472
Drug-induced Neurotoxicity:  0.092 Ototoxicity:  0.548
Hematotoxicity:  0.038 Drug-induced Nephrotoxicity:  0.07
Genotoxicity:  0.626 RPMI-8226 Immunitoxicity:  0.018
A549 Cytotoxicity:  0.723 Hek293 Cytotoxicity:  0.776
BCF:   1.166
?
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:   4.223
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.244
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.041
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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
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/np100392m]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota rhizomes Kampaengsaen district, Nakhon Pathom province, Thailand n.a. PMID[18554915]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota aerial parts n.a. n.a. PMID[20196571]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota rhizomes n.a. n.a. PMID[23707257]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[23910596]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[8176399]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22901 Curcuma comosa Species Zingiberaceae 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
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition < 17.0 % PMID[22295903]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT34 Cell line BV-2 Mus musculus Activity = 103.61 % PMID[26402726]
NPT34 Cell line BV-2 Mus musculus IC50 = 14360.0 nM Open TG-GATES in vivo data: Biochemistry
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 16.3 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 23.4 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 30.5 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 37.8 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 27.8 % PMID[23910596]

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 NPC277394 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
0.8636 High Similarity NPC299252
0.8605 High Similarity NPC69332
0.766 Intermediate Similarity NPC95178
0.72 Intermediate Similarity NPC19290
0.6981 Remote Similarity NPC151167
0.6923 Remote Similarity NPC485985
0.6 Remote Similarity NPC276466
0.5833 Remote Similarity NPC139901
0.5818 Remote Similarity NPC86900
0.5714 Remote Similarity NPC470848
0.5625 Remote Similarity NPC29989
0.5625 Remote Similarity NPC51698
0.5577 Remote Similarity NPC88141
0.5472 Remote Similarity NPC70843
0.5306 Remote Similarity NPC201967
0.5283 Remote Similarity NPC120693
0.52 Remote Similarity NPC61062
0.5192 Remote Similarity NPC49529
0.5179 Remote Similarity NPC23402
0.5111 Remote Similarity NPC260000
0.5091 Remote Similarity NPC297657

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC277394 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