Natural Product: NPC179726

Natural Product IDNPC179726
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1E,6E)-1,7-Diphenylhepta-1,6-Diene-3,5-Dione
IUPAC Name (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL102914
PubChem CID 5469422
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 UXLWOYFDJVFCBR-PHEQNACWSA-N
Standard InCHI InChI=1S/C19H16O2/c20-18(13-11-16-7-3-1-4-8-16)15-19(21)14-12-17-9-5-2-6-10-17/h1-14H,15H2/b13-11+,14-12+
SMILES O=C(CC(=O)/C=C/c1ccccc1)/C=C/c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   276.12 Volume:   311.283
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Van der Waals volume.
Dense:   0.887 LogP:   3.315
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.404
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.47
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   16.0
TPSA:   34.14
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.591 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.031 Fsp3:   0.053
MCE-18:   10.0
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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:   1.0 Fluc inhibitor:   1.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.059
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.752
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.998 Promiscuous compounds:   0.297

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.914 MDCK Permeability:   -4.651
Pgp-inhibitor:   0.984 Pgp-substrate:   0.001
PAMPA:   0.129
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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):   0.001
20% Bioavailability (F20%):   0.088 30% Bioavailability (F30%):   0.332
50% Bioavailability (F50%):   0.888

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.986 MRP1:   0.38
Plasma Protein Binding (PPB):   98.013% Volume Distribution (VD):   -0.449
Fu: 1.605%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.949
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.004
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.99
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.731
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.314
CYP2D6-inhibitor:   0.902 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.053
?
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):  11.792 Half-life (T1/2):  0.679

ADMET: Toxicity

hERG Blockers:  0.744 hERG Blockers (10um):  0.681
Human Hepatotoxicity (H-HT):  0.605 Drug-induced Liver Injury (DILI):  0.113
AMES Toxicity:  0.199 Rat Oral Acute Toxicity:  0.043
Maximum Recommended Daily Dose:  0.442 Skin Sensitization:  0.996
Carcinogencity:  0.036 Eye Corrosion:  0.073
Eye Irritation:  0.967 Respiratory Toxicity:  0.612
Drug-induced Neurotoxicity:  0.812 Ototoxicity:  0.042
Hematotoxicity:  0.017 Drug-induced Nephrotoxicity:  0.169
Genotoxicity:  0.117 RPMI-8226 Immunitoxicity:  0.031
A549 Cytotoxicity:  0.571 Hek293 Cytotoxicity:  0.573
BCF:   1.052
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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:   4.365
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.455
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.312
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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
NPO21600 Aconitum variegatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20584 Cheilanthes fragrans Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21344 Fadogia agrestis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21534 Ostrya carpinifolia Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22500 Stephania dielsiana Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21600 Aconitum variegatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22500 Stephania dielsiana Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21600 Aconitum variegatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22500 Stephania dielsiana Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21600 Aconitum variegatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21534 Ostrya carpinifolia Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21344 Fadogia agrestis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22500 Stephania dielsiana Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21600 Aconitum variegatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20584 Cheilanthes fragrans Species Pteridaceae 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
NPT12 Individual protein Human immunodeficiency virus type 1 integrase Human immunodeficiency virus 1 IC50 > 300000.0 nM PMID[9301668]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens IC50 > 200000.0 nM PMID[26894841]
NPT71 Cell line HEK293 Homo sapiens CC50 > 20000.0 nM PMID[36608774]
NPT1018 Organism Trypanosoma brucei Trypanosoma brucei EC50 > 4000.0 nM PMID[36608774]

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 NPC179726 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
0.7037 Intermediate Similarity NPC311343
0.6333 Remote Similarity NPC95289
0.625 Remote Similarity NPC68269
0.5714 Remote Similarity NPC17497
0.5714 Remote Similarity NPC305602
0.5517 Remote Similarity NPC169222
0.5517 Remote Similarity NPC235059
0.5517 Remote Similarity NPC16190
0.5429 Remote Similarity NPC185738
0.5405 Remote Similarity NPC51698
0.5185 Remote Similarity NPC269586

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC179726 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
0.5429 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