Natural Product: NPC207613

Natural Product IDNPC207613
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-[(E,3S)-3-Hydroxy-7-(4-Hydroxyphenyl)Hept-6-Enyl]-2-Methoxyphenol
IUPAC Name 4-[(E,3S)-3-hydroxy-7-(4-hydroxyphenyl)hept-6-enyl]-2-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2426106
PubChem CID 72164689
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 RDXGNAHMAOEPKS-WVMJFEGXSA-N
Standard InCHI InChI=1S/C20H24O4/c1-24-20-14-16(9-13-19(20)23)8-12-17(21)5-3-2-4-15-6-10-18(22)11-7-15/h2,4,6-7,9-11,13-14,17,21-23H,3,5,8,12H2,1H3/b4-2+/t17-/m0/s1
SMILES COc1cc(CC[C@H](CC/C=C/c2ccc(cc2)O)O)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.17 Volume:   354.069
?
Van der Waals volume.
Dense:   0.927 LogP:   3.423
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.515
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.837
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   13.0
TPSA:   69.92
?
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:   0.687 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.704 Fsp3:   0.3
MCE-18:   24.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.583 Fluc inhibitor:   0.803
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.419
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.595 Promiscuous compounds:   0.362

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.189 MDCK Permeability:   -4.913
Pgp-inhibitor:   0.752 Pgp-substrate:   0.034
PAMPA:   0.003
?
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%):   0.878 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.065
Plasma Protein Binding (PPB):   88.886% Volume Distribution (VD):   -0.521
Fu: 8.028%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.899
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.028 CYP1A2-substrate:   0.006
CYP2C19-inhibitor:   0.956 CYP2C19-substrate:   0.007
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.086
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.171
CYP3A4-inhibitor:   0.509 CYP3A4-substrate:   0.124
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.687
?
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):  9.425 Half-life (T1/2):  1.164

ADMET: Toxicity

hERG Blockers:  0.513 hERG Blockers (10um):  0.811
Human Hepatotoxicity (H-HT):  0.827 Drug-induced Liver Injury (DILI):  0.045
AMES Toxicity:  0.198 Rat Oral Acute Toxicity:  0.024
Maximum Recommended Daily Dose:  0.94 Skin Sensitization:  0.922
Carcinogencity:  0.1 Eye Corrosion:  0.007
Eye Irritation:  0.848 Respiratory Toxicity:  0.553
Drug-induced Neurotoxicity:  0.316 Ototoxicity:  0.752
Hematotoxicity:  0.107 Drug-induced Nephrotoxicity:  0.811
Genotoxicity:  0.038 RPMI-8226 Immunitoxicity:  0.08
A549 Cytotoxicity:  0.32 Hek293 Cytotoxicity:  0.726
BCF:   1.339
?
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:   3.906
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.152
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.675
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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]
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]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 37.8 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 27.2 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 28.9 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 8.9 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 13.7 % 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 NPC207613 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
0.7255 Intermediate Similarity NPC216468
0.7255 Intermediate Similarity NPC78119
0.6727 Remote Similarity NPC147634
0.6727 Remote Similarity NPC79793
0.6667 Remote Similarity NPC473853
0.6667 Remote Similarity NPC470212
0.6545 Remote Similarity NPC51333
0.6226 Remote Similarity NPC312675
0.6226 Remote Similarity NPC262156
0.6226 Remote Similarity NPC184651
0.6226 Remote Similarity NPC113865
0.6167 Remote Similarity NPC215941
0.6167 Remote Similarity NPC123196
0.6167 Remote Similarity NPC311419
0.614 Remote Similarity NPC164386
0.6 Remote Similarity NPC310718
0.5873 Remote Similarity NPC90128
0.5862 Remote Similarity NPC343720
0.5862 Remote Similarity NPC54872
0.5789 Remote Similarity NPC98631
0.5789 Remote Similarity NPC206615
0.5763 Remote Similarity NPC137427
0.569 Remote Similarity NPC324571
0.5667 Remote Similarity NPC311595
0.5667 Remote Similarity NPC481913
0.5667 Remote Similarity NPC24474
0.5593 Remote Similarity NPC55617
0.5593 Remote Similarity NPC62258
0.5469 Remote Similarity NPC65935
0.5469 Remote Similarity NPC319282
0.5345 Remote Similarity NPC186843
0.5312 Remote Similarity NPC275724
0.5312 Remote Similarity NPC244246
0.5312 Remote Similarity NPC611247
0.5254 Remote Similarity NPC481914
0.5179 Remote Similarity NPC164449
0.5179 Remote Similarity NPC184030
0.5167 Remote Similarity NPC285350
0.5156 Remote Similarity NPC304622
0.5094 Remote Similarity NPC8547
0.5085 Remote Similarity NPC71941
0.5077 Remote Similarity NPC84076
0.5077 Remote Similarity NPC151167

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC207613 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