Natural Product: NPC177160

Natural Product IDNPC177160
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S,3R)-5-Allyl-7-Methoxy-3-Hydroxymethyl-2-(3'-Methoxy-4'-Hydroxyphenyl)-2,3-Dihydrobenzofuran
IUPAC Name 4-[(2S,3R)-3-(hydroxymethyl)-7-methoxy-5-prop-2-enyl-2,3-dihydro-1-benzofuran-2-yl]-2-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL457269
PubChem CID 14258445
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 SCJINMBKEKPVHB-HNAYVOBHSA-N
Standard InCHI InChI=1S/C20H22O5/c1-4-5-12-8-14-15(11-21)19(25-20(14)18(9-12)24-3)13-6-7-16(22)17(10-13)23-2/h4,6-10,15,19,21-22H,1,5,11H2,2-3H3/t15-,19+/m0/s1
SMILES C=CCc1cc2c(c(c1)OC)O[C@@H]([C@H]2CO)c1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   342.15 Volume:   354.303
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Van der Waals volume.
Dense:   0.966 LogP:   3.137
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.047
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.016
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   68.15
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.788 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.37 Fsp3:   0.3
MCE-18:   56.769
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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:   0.458 Fluc inhibitor:   0.694
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.033
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.235
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.247 Promiscuous compounds:   0.28

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.609 MDCK Permeability:   -4.619
Pgp-inhibitor:   0.896 Pgp-substrate:   0.001
PAMPA:   0.001
?
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):   0.006
20% Bioavailability (F20%):   0.631 30% Bioavailability (F30%):   0.929
50% Bioavailability (F50%):   0.979

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.044 MRP1:   0.571
Plasma Protein Binding (PPB):   85.356% Volume Distribution (VD):   0.239
Fu: 16.091%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.954
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.736 CYP1A2-substrate:   0.344
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.419
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.006 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   1.0
HLM stability:   0.039
?
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):  8.106 Half-life (T1/2):  1.809

ADMET: Toxicity

hERG Blockers:  0.08 hERG Blockers (10um):  0.418
Human Hepatotoxicity (H-HT):  0.628 Drug-induced Liver Injury (DILI):  0.317
AMES Toxicity:  0.55 Rat Oral Acute Toxicity:  0.414
Maximum Recommended Daily Dose:  0.379 Skin Sensitization:  0.97
Carcinogencity:  0.466 Eye Corrosion:  0.118
Eye Irritation:  0.973 Respiratory Toxicity:  0.68
Drug-induced Neurotoxicity:  0.579 Ototoxicity:  0.479
Hematotoxicity:  0.295 Drug-induced Nephrotoxicity:  0.297
Genotoxicity:  0.321 RPMI-8226 Immunitoxicity:  0.085
A549 Cytotoxicity:  0.348 Hek293 Cytotoxicity:  0.452
BCF:   1.056
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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:   3.603
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.952
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.343
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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
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota stems Honghe Prefecture of Yunnan Province, China 2005-Oct PMID[18278869]
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[21232955]
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18146 Kadsura angustifolia Species Schisandraceae 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
NPT1452 Cell line C8166 Homo sapiens CC50 = 38070.0 nM PMID[17125239]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 13070.0 nM PMID[19555123]
NPT2 Others Unspecified n.a. Ratio = 2.91 n.a. PMID[18973387]

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 NPC177160 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
0.7895 Intermediate Similarity NPC29799
0.7895 Intermediate Similarity NPC263367
0.7895 Intermediate Similarity NPC54743
0.7069 Intermediate Similarity NPC300757
0.7 Intermediate Similarity NPC156502
0.7 Intermediate Similarity NPC10737
0.6774 Remote Similarity NPC284881
0.6774 Remote Similarity NPC93433
0.6774 Remote Similarity NPC474444
0.6613 Remote Similarity NPC472961
0.6613 Remote Similarity NPC472962
0.6562 Remote Similarity NPC253878
0.6562 Remote Similarity NPC206413
0.6562 Remote Similarity NPC482649
0.6562 Remote Similarity NPC149003
0.6562 Remote Similarity NPC471414
0.6562 Remote Similarity NPC482647
0.6562 Remote Similarity NPC482648
0.6562 Remote Similarity NPC482651
0.6562 Remote Similarity NPC194244
0.6562 Remote Similarity NPC482650
0.6364 Remote Similarity NPC163898
0.5833 Remote Similarity NPC481090
0.5806 Remote Similarity NPC187616
0.5806 Remote Similarity NPC193026
0.5806 Remote Similarity NPC49603
0.5769 Remote Similarity NPC224674
0.5769 Remote Similarity NPC64475
0.5714 Remote Similarity NPC230219
0.5714 Remote Similarity NPC87725
0.5714 Remote Similarity NPC263261
0.5714 Remote Similarity NPC180901
0.5455 Remote Similarity NPC473408
0.5441 Remote Similarity NPC209985
0.5152 Remote Similarity NPC26394
0.5128 Remote Similarity NPC260397
0.5094 Remote Similarity NPC257124
0.5063 Remote Similarity NPC193473
0.5063 Remote Similarity NPC600128

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC177160 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
0.5094 Remote Similarity NPD228 Phase 0

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