Natural Product: NPC18984

Natural Product IDNPC18984
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1,7-Bis(4-Hydroxy-3-Methoxyphenyl)Hepta-1,6-Diene-3,5-Dione
IUPAC Name 1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3187799
PubChem CID 2889
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids
          • [CHEMONTID:0000356] Curcuminoids

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 VFLDPWHFBUODDF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)13-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h3-12,24-25H,13H2,1-2H3
SMILES COc1cc(C=CC(=O)CC(=O)C=Cc2ccc(c(c2)OC)O)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.13 Volume:   381.036
?
Van der Waals volume.
Dense:   0.966 LogP:   2.374
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.649
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.831
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   16.0
TPSA:   93.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.548 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.426 Fsp3:   0.143
MCE-18:   14.0
?
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:   0.991 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.149
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.766
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.619 Promiscuous compounds:   0.077

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.417 MDCK Permeability:   -4.936
Pgp-inhibitor:   0.022 Pgp-substrate:   0.004
PAMPA:   0.124
?
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):   0.005
20% Bioavailability (F20%):   0.485 30% Bioavailability (F30%):   0.465
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.03 MRP1:   0.881
Plasma Protein Binding (PPB):   90.858% Volume Distribution (VD):   -0.525
Fu: 6.785%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.286
BSEP inhibitor:   0.641

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.257
CYP2C19-inhibitor:   0.425 CYP2C19-substrate:   0.034
CYP2C9-inhibitor:   0.013 CYP2C9-substrate:   0.025
CYP2D6-inhibitor:   0.97 CYP2D6-substrate:   0.885
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.992
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.928
?
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):  9.635 Half-life (T1/2):  1.196

ADMET: Toxicity

hERG Blockers:  0.41 hERG Blockers (10um):  0.707
Human Hepatotoxicity (H-HT):  0.34 Drug-induced Liver Injury (DILI):  0.01
AMES Toxicity:  0.411 Rat Oral Acute Toxicity:  0.177
Maximum Recommended Daily Dose:  0.325 Skin Sensitization:  0.998
Carcinogencity:  0.124 Eye Corrosion:  0.052
Eye Irritation:  0.863 Respiratory Toxicity:  0.744
Drug-induced Neurotoxicity:  0.395 Ototoxicity:  0.188
Hematotoxicity:  0.038 Drug-induced Nephrotoxicity:  0.27
Genotoxicity:  0.015 RPMI-8226 Immunitoxicity:  0.105
A549 Cytotoxicity:  0.628 Hek293 Cytotoxicity:  0.652
BCF:   0.68
?
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:   3.348
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.159
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.755
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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
NPO9241 Adiantum capillus-veneris Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7308 Fraxinus quadrangulata Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25160 Goniothalamus borneensis Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3251 Jacobaea maritima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3532 Tridentata marginata n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO9241 Adiantum capillus-veneris Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7308 Fraxinus quadrangulata Species Oleaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7308 Fraxinus quadrangulata Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9241 Adiantum capillus-veneris Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3251 Jacobaea maritima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9241 Adiantum capillus-veneris Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25160 Goniothalamus borneensis Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3532 Tridentata marginata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO9241 Adiantum capillus-veneris Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7308 Fraxinus quadrangulata Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3251 Jacobaea maritima Species Asteraceae 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

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 NPC18984 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
1.0 High Similarity NPC160900
0.8974 High Similarity NPC71941
0.875 High Similarity NPC106659
0.8158 Intermediate Similarity NPC224814
0.7447 Intermediate Similarity NPC304622
0.7381 Intermediate Similarity NPC14007
0.7292 Intermediate Similarity NPC474784
0.7105 Intermediate Similarity NPC36108
0.7105 Intermediate Similarity NPC233731
0.7105 Intermediate Similarity NPC610203
0.7 Intermediate Similarity NPC39793
0.6889 Remote Similarity NPC60962
0.6667 Remote Similarity NPC107588
0.6667 Remote Similarity NPC137537
0.6596 Remote Similarity NPC109083
0.6585 Remote Similarity NPC78918
0.6585 Remote Similarity NPC139617
0.6471 Remote Similarity NPC253455
0.6458 Remote Similarity NPC110313
0.6316 Remote Similarity NPC246358
0.6154 Remote Similarity NPC68269
0.6122 Remote Similarity NPC70752
0.6087 Remote Similarity NPC202474
0.6078 Remote Similarity NPC189844
0.5957 Remote Similarity NPC66905
0.5882 Remote Similarity NPC276466
0.5882 Remote Similarity NPC158949
0.5854 Remote Similarity NPC159418
0.5854 Remote Similarity NPC185738
0.5849 Remote Similarity NPC269843
0.5833 Remote Similarity NPC246704
0.5789 Remote Similarity NPC471110
0.5745 Remote Similarity NPC276014
0.5686 Remote Similarity NPC83062
0.5686 Remote Similarity NPC15621
0.566 Remote Similarity NPC84076
0.566 Remote Similarity NPC151167
0.56 Remote Similarity NPC289459
0.56 Remote Similarity NPC254659
0.549 Remote Similarity NPC204466
0.549 Remote Similarity NPC485638
0.549 Remote Similarity NPC186898
0.5455 Remote Similarity NPC71579
0.5455 Remote Similarity NPC271785
0.5455 Remote Similarity NPC51698
0.5435 Remote Similarity NPC70744
0.5424 Remote Similarity NPC472410
0.54 Remote Similarity NPC148627
0.537 Remote Similarity NPC60517
0.537 Remote Similarity NPC146886
0.537 Remote Similarity NPC135127
0.537 Remote Similarity NPC20443
0.5333 Remote Similarity NPC56332
0.5333 Remote Similarity NPC10932
0.5333 Remote Similarity NPC606519
0.52 Remote Similarity NPC103823
0.5185 Remote Similarity NPC213552
0.5185 Remote Similarity NPC120225
0.5179 Remote Similarity NPC482462
0.5128 Remote Similarity NPC7097
0.5122 Remote Similarity NPC203719
0.5106 Remote Similarity NPC142985
0.5106 Remote Similarity NPC127937

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC18984 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
1.0 High Similarity NPD4379 Clinical (unspecified phase)
0.5854 Remote Similarity NPD5536 Phase 2

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