Natural Product: NPC95716

Natural Product IDNPC95716
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Effusol
IUPAC Name 5-ethenyl-1-methyl-9,10-dihydrophenanthrene-2,7-diol
Synonyms NSC-371300
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL205119
PubChem CID 100801
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 GEXAPRXWKRZPCK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H16O2/c1-3-11-8-13(18)9-12-4-5-14-10(2)16(19)7-6-15(14)17(11)12/h3,6-9,18-19H,1,4-5H2,2H3
SMILES C=Cc1cc(cc2CCc3c(C)c(ccc3-c12)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   252.12 Volume:   276.044
?
Van der Waals volume.
Dense:   0.913 LogP:   3.349
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.221
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.15
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.81 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.828 Fsp3:   0.176
MCE-18:   37.4
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.813 Fluc inhibitor:   0.117
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.67
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.206
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.568 Promiscuous compounds:   0.071

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.972 MDCK Permeability:   -4.803
Pgp-inhibitor:   0.136 Pgp-substrate:   0.208
PAMPA:   0.18
?
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):   0.004
20% Bioavailability (F20%):   0.428 30% Bioavailability (F30%):   0.658
50% Bioavailability (F50%):   0.958

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.175 MRP1:   0.889
Plasma Protein Binding (PPB):   93.694% Volume Distribution (VD):   0.737
Fu: 7.225%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.944
OATP1B3 inhibitor:   0.911 BCRP inhibitor:   0.686
BSEP inhibitor:   0.835

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.979
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.921
CYP2C9-inhibitor:   0.956 CYP2C9-substrate:   0.024
CYP2D6-inhibitor:   0.741 CYP2D6-substrate:   0.99
CYP3A4-inhibitor:   0.889 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.048 CYP2C8-inhibitor:   1.0
HLM stability:   0.862
?
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):  9.961 Half-life (T1/2):  1.013

ADMET: Toxicity

hERG Blockers:  0.164 hERG Blockers (10um):  0.646
Human Hepatotoxicity (H-HT):  0.641 Drug-induced Liver Injury (DILI):  0.233
AMES Toxicity:  0.77 Rat Oral Acute Toxicity:  0.597
Maximum Recommended Daily Dose:  0.658 Skin Sensitization:  0.968
Carcinogencity:  0.793 Eye Corrosion:  0.092
Eye Irritation:  0.976 Respiratory Toxicity:  0.962
Drug-induced Neurotoxicity:  0.703 Ototoxicity:  0.492
Hematotoxicity:  0.272 Drug-induced Nephrotoxicity:  0.159
Genotoxicity:  0.723 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.423 Hek293 Cytotoxicity:  0.62
BCF:   1.776
?
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:   4.803
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.525
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.216
?
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
NPO40173 Juncus inflexus Species Juncaceae Eukaryota n.a. n.a. n.a. PMID[27808510]
NPO1150 Juncus effusus Species Juncaceae Eukaryota n.a. n.a. n.a. PMID[30892891]
NPO1150 Juncus effusus Species Juncaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1150 Juncus effusus Species Juncaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1150 Juncus effusus Species Juncaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1150 Juncus effusus Species Juncaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1150 Juncus effusus Species Juncaceae 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
NPT108 Individual protein Estrogen receptor alpha Homo sapiens IC50 = 240.0 nM PMID[16412638]
NPT248 Individual protein Estrogen receptor beta Homo sapiens IC50 = 12.0 nM PMID[16412638]
NPT2981 Individual protein dTDP-4-dehydrorhamnose reductase Mycobacterium tuberculosis IC50 = 25000.0 nM PMID[22014548]
NPT669 Individual protein Solute carrier family 22 member 8 Homo sapiens Inhibition > 50.0 % PMID[30892891]
NPT669 Individual protein Solute carrier family 22 member 8 Homo sapiens IC50 = 22700.0 nM PMID[30892891]
NPT665 Individual protein Solute carrier family 22 member 6 Homo sapiens IC50 = 23300.0 nM PMID[30892891]
NPT665 Individual protein Solute carrier family 22 member 6 Homo sapiens Inhibition > 50.0 % PMID[30892891]
NPT544 Protein family Estrogen receptor Homo sapiens Ratio IC50 = 20.0 n.a. PMID[16412638]

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 = 15100.0 nM PMID[29280630]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus Ratio = 16.0 n.a. PMID[27808510]
NPT790 Organism Mycobacterium tuberculosis H37Rv Mycobacterium tuberculosis H37Rv MIC = 20.0 ug.mL-1 PMID[22014548]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity = 7.8 n.a. PMID[29280630]
NPT32 Organism Mus musculus Mus musculus TIME = 0.02097 hr PMID[29280630]





 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 NPC95716 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
0.7073 Intermediate Similarity NPC46940
0.625 Remote Similarity NPC483362
0.58 Remote Similarity NPC29980
0.5682 Remote Similarity NPC311518
0.5625 Remote Similarity NPC603244

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC95716 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