Natural Product: NPC138942

Natural Product IDNPC138942
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,5'-Dipropylbiphenyl-2,2'-Diol
IUPAC Name 2-(2-hydroxy-5-propylphenyl)-4-propylphenol
Synonyms tetrahydro-magnolol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL32362
PubChem CID 5321851
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000041] Biphenyls and derivatives

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 OYAQUBKYAKSHOA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H22O2/c1-3-5-13-7-9-17(19)15(11-13)16-12-14(6-4-2)8-10-18(16)20/h7-12,19-20H,3-6H2,1-2H3
SMILES CCCc1ccc(c(c1)c1cc(CCC)ccc1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   270.16 Volume:   304.533
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Van der Waals volume.
Dense:   0.887 LogP:   4.834
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.69
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.448
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   12.0
TPSA:   40.46
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.828 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.066 Fsp3:   0.333
MCE-18:   12.0
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.869 Fluc inhibitor:   0.061
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.68
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.04
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.794 Promiscuous compounds:   0.055

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.482 MDCK Permeability:   -4.687
Pgp-inhibitor:   0.026 Pgp-substrate:   0.78
PAMPA:   0.228
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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):   0.155
20% Bioavailability (F20%):   0.657 30% Bioavailability (F30%):   0.63
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.048 MRP1:   0.79
Plasma Protein Binding (PPB):   99.644% Volume Distribution (VD):   0.802
Fu: 0.493%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.961
OATP1B3 inhibitor:   0.903 BCRP inhibitor:   0.737
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.792 CYP1A2-substrate:   0.958
CYP2C19-inhibitor:   0.922 CYP2C19-substrate:   0.074
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.005 CYP3A4-substrate:   0.026
CYP2B6-substrate:   0.035 CYP2C8-inhibitor:   1.0
HLM stability:   0.048
?
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):  10.156 Half-life (T1/2):  1.109

ADMET: Toxicity

hERG Blockers:  0.455 hERG Blockers (10um):  0.883
Human Hepatotoxicity (H-HT):  0.597 Drug-induced Liver Injury (DILI):  0.133
AMES Toxicity:  0.205 Rat Oral Acute Toxicity:  0.216
Maximum Recommended Daily Dose:  0.431 Skin Sensitization:  0.916
Carcinogencity:  0.159 Eye Corrosion:  0.595
Eye Irritation:  0.977 Respiratory Toxicity:  0.75
Drug-induced Neurotoxicity:  0.171 Ototoxicity:  0.513
Hematotoxicity:  0.272 Drug-induced Nephrotoxicity:  0.568
Genotoxicity:  0.003 RPMI-8226 Immunitoxicity:  0.148
A549 Cytotoxicity:  0.848 Hek293 Cytotoxicity:  0.672
BCF:   1.634
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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:   4.492
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.2
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.777
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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
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[1659613]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota stem bark n.a. n.a. PMID[17918910]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota Stems; Barks n.a. n.a. PMID[19086868]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. bark n.a. PMID[23823874]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[28485933]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[7463094]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[8201313]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[8699182]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17566 Magnolia biloba Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17566 Magnolia biloba Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17566 Magnolia biloba Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17566 Magnolia biloba Species Magnoliaceae 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
NPT2552 Individual protein Calcium-activated potassium channel subunit alpha-1 Homo sapiens Control current = 95.9 % PMID[12668007]
NPT1287 Individual protein Cannabinoid CB2 receptor Homo sapiens Ratio EC50 = 19.0 n.a. PMID[24900561]
NPT1287 Individual protein Cannabinoid CB2 receptor Homo sapiens Efficacy = 49.0 % PMID[24900561]
NPT232 Individual protein Cannabinoid CB1 receptor Homo sapiens Efficacy = 124.0 % PMID[24900561]
NPT232 Individual protein Cannabinoid CB1 receptor Homo sapiens EC50 = 9010.0 nM PMID[24900561]
NPT1287 Individual protein Cannabinoid CB2 receptor Homo sapiens Ki = 416.0 nM PMID[24900561]
NPT232 Individual protein Cannabinoid CB1 receptor Homo sapiens Ki = 2260.0 nM PMID[24900561]
NPT1287 Individual protein Cannabinoid CB2 receptor Homo sapiens EC50 = 170.0 nM PMID[24900561]
NPT4120 Individual protein G-protein coupled receptor 55 Homo sapiens Kb = 13300.0 nM PMID[24900561]
NPT4120 Individual protein G-protein coupled receptor 55 Homo sapiens Inhibition = 96.0 % PMID[24900561]

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 = 23400.0 nM PMID[15582432]

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 NPC138942 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
0.6452 Remote Similarity NPC288411
0.6216 Remote Similarity NPC473136
0.575 Remote Similarity NPC262365
0.575 Remote Similarity NPC602856
0.5676 Remote Similarity NPC473137
0.5667 Remote Similarity NPC608485
0.561 Remote Similarity NPC286222
0.5556 Remote Similarity NPC488678
0.5349 Remote Similarity NPC488675
0.5349 Remote Similarity NPC182240
0.5263 Remote Similarity NPC95344
0.5227 Remote Similarity NPC488578
0.5227 Remote Similarity NPC231767
0.5227 Remote Similarity NPC601260
0.5227 Remote Similarity NPC608771
0.5227 Remote Similarity NPC608772
0.5128 Remote Similarity NPC295034
0.5128 Remote Similarity NPC308689
0.5122 Remote Similarity NPC12656
0.5122 Remote Similarity NPC488674

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC138942 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