Natural Product: NPC160697

Natural Product IDNPC160697
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Epheneranthol C
IUPAC Name 4-methoxy-9,10-dihydrophenanthrene-2,3,5-triol
Synonyms Epheneranthol C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1085501
PubChem CID 46871898
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000025] Phenanthrenes and derivatives
        • [CHEMONTID:0000223] Hydrophenanthrenes

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 LOICISWPCCICIA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H14O4/c1-19-15-13-9(7-11(17)14(15)18)6-5-8-3-2-4-10(16)12(8)13/h2-4,7,16-18H,5-6H2,1H3
SMILES COc1c2c(CCc3c2c(O)ccc3)cc(c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   258.09 Volume:   261.669
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Van der Waals volume.
Dense:   0.986 LogP:   2.502
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.5
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.547
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   16.0
TPSA:   69.92
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.688 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.529 Fsp3:   0.2
MCE-18:   37.778
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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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.778 Fluc inhibitor:   0.196
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.634
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.21
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.39 Promiscuous compounds:   0.289

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.982 MDCK Permeability:   -4.749
Pgp-inhibitor:   0.002 Pgp-substrate:   0.113
PAMPA:   0.897
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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):   0.186
20% Bioavailability (F20%):   0.834 30% Bioavailability (F30%):   0.921
50% Bioavailability (F50%):   0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.135 MRP1:   0.975
Plasma Protein Binding (PPB):   95.407% Volume Distribution (VD):   -0.332
Fu: 6.374%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.679
OATP1B3 inhibitor:   0.871 BCRP inhibitor:   0.184
BSEP inhibitor:   0.234

ADMET: Metabolism

CYP1A2-inhibitor:   0.184 CYP1A2-substrate:   0.02
CYP2C19-inhibitor:   0.022 CYP2C19-substrate:   0.582
CYP2C9-inhibitor:   0.934 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.921 CYP2D6-substrate:   0.059
CYP3A4-inhibitor:   0.032 CYP3A4-substrate:   0.444
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.842
HLM stability:   0.934
?
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):  11.809 Half-life (T1/2):  1.419

ADMET: Toxicity

hERG Blockers:  0.097 hERG Blockers (10um):  0.604
Human Hepatotoxicity (H-HT):  0.551 Drug-induced Liver Injury (DILI):  0.289
AMES Toxicity:  0.71 Rat Oral Acute Toxicity:  0.415
Maximum Recommended Daily Dose:  0.526 Skin Sensitization:  0.949
Carcinogencity:  0.514 Eye Corrosion:  0.013
Eye Irritation:  0.936 Respiratory Toxicity:  0.905
Drug-induced Neurotoxicity:  0.175 Ototoxicity:  0.538
Hematotoxicity:  0.203 Drug-induced Nephrotoxicity:  0.276
Genotoxicity:  0.496 RPMI-8226 Immunitoxicity:  0.065
A549 Cytotoxicity:  0.683 Hek293 Cytotoxicity:  0.381
BCF:   1.479
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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:   4.141
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.292
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.736
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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
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[11575955]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. n.a. n.a. PMID[16268553]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. Fijian red alga n.a. PMID[16724831]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota stems Yunnan Province, China 2004 PMID[17253844]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. n.a. n.a. PMID[17715978]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota Stems purchased from Kyoungdong Oriental Herbal Market, Seoul, Korea 2006-APR PMID[18052323]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. Fijian red alga n.a. PMID[20141173]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota Stems n.a. n.a. PMID[27310249]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. n.a. n.a. PMID[30407005]
NPO11242 Gynochthodes parvifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15662 Ligustrum ovalifolium Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13053 Corydalis conspersa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5019 Mespilus germanica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1575 Mikania luetzelburgii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO326 Pittosporum brevicalyx Species Pittosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15280 Sideritis grandiflora Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6178 Solanum euacanthum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4581 Ungernia victoris Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5019 Mespilus germanica Species Rosaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5019 Mespilus germanica Species Rosaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO11242 Gynochthodes parvifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6178 Solanum euacanthum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1575 Mikania luetzelburgii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5019 Mespilus germanica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15280 Sideritis grandiflora Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4581 Ungernia victoris Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11242 Gynochthodes parvifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15662 Ligustrum ovalifolium Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO326 Pittosporum brevicalyx Species Pittosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13053 Corydalis conspersa Species Papaveraceae 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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 17600.0 nM PMID[20483604]

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 NPC160697 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
0.6889 Remote Similarity NPC105718
0.6889 Remote Similarity NPC90740
0.6739 Remote Similarity NPC143139
0.6122 Remote Similarity NPC79622
0.587 Remote Similarity NPC278955

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC160697 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