Natural Product: NPC54743

Natural Product IDNPC54743
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (7S,8S)-Dihydrodehydrodiconiferyl Alcohol
IUPAC Name 4-[(2S,3S)-3-(hydroxymethyl)-5-(3-hydroxypropyl)-7-methoxy-2,3-dihydro-1-benzofuran-2-yl]-2-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3098865
PubChem CID 11595642
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 SBLZVJIHPWRSQQ-DNVCBOLYSA-N
Standard InCHI InChI=1S/C20H24O6/c1-24-17-10-13(5-6-16(17)23)19-15(11-22)14-8-12(4-3-7-21)9-18(25-2)20(14)26-19/h5-6,8-10,15,19,21-23H,3-4,7,11H2,1-2H3/t15-,19-/m1/s1
SMILES OCCCc1cc2c(c(c1)OC)O[C@@H]([C@@H]2CO)c1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.16 Volume:   365.729
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Van der Waals volume.
Dense:   0.985 LogP:   2.254
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.445
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.429
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   16.0
TPSA:   88.38
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.703 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.267 Fsp3:   0.4
MCE-18:   56.571
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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:   0
Colloidal aggregators:   0.272 Fluc inhibitor:   0.66
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.035
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.356
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.074 Promiscuous compounds:   0.22

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.205 MDCK Permeability:   -4.897
Pgp-inhibitor:   0.674 Pgp-substrate:   0.582
PAMPA:   0.112
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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):   0.03
20% Bioavailability (F20%):   0.156 30% Bioavailability (F30%):   0.278
50% Bioavailability (F50%):   0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.022 MRP1:   0.68
Plasma Protein Binding (PPB):   75.544% Volume Distribution (VD):   -0.19
Fu: 24.672%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.694
BSEP inhibitor:   0.973

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.971 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.97 CYP2D6-substrate:   0.814
CYP3A4-inhibitor:   0.939 CYP3A4-substrate:   0.066
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
HLM stability:   0.001
?
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):  6.306 Half-life (T1/2):  1.506

ADMET: Toxicity

hERG Blockers:  0.096 hERG Blockers (10um):  0.384
Human Hepatotoxicity (H-HT):  0.824 Drug-induced Liver Injury (DILI):  0.109
AMES Toxicity:  0.461 Rat Oral Acute Toxicity:  0.184
Maximum Recommended Daily Dose:  0.104 Skin Sensitization:  0.785
Carcinogencity:  0.344 Eye Corrosion:  0.012
Eye Irritation:  0.973 Respiratory Toxicity:  0.248
Drug-induced Neurotoxicity:  0.152 Ototoxicity:  0.773
Hematotoxicity:  0.429 Drug-induced Nephrotoxicity:  0.71
Genotoxicity:  0.151 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.093 Hek293 Cytotoxicity:  0.248
BCF:   0.67
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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:   3.133
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.744
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.839
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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
NPO31082 Pulsatilla koreana Species Ranunculaceae Eukaryota n.a. root n.a. PMID[15473660]
NPO31082 Pulsatilla koreana Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[15730260]
NPO31082 Pulsatilla koreana Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[24360605]
NPO31082 Pulsatilla koreana Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT2 Others Unspecified n.a. IC50 = 35900.0 nM PMID[15620242]

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 NPC54743 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
1.0 High Similarity NPC29799
1.0 High Similarity NPC263367
0.7895 Intermediate Similarity NPC177160
0.7368 Intermediate Similarity NPC230219
0.7069 Intermediate Similarity NPC300757
0.6721 Remote Similarity NPC156502
0.6721 Remote Similarity NPC10737
0.6613 Remote Similarity NPC472961
0.6613 Remote Similarity NPC472962
0.6508 Remote Similarity NPC284881
0.6508 Remote Similarity NPC93433
0.6508 Remote Similarity NPC474444
0.64 Remote Similarity NPC224674
0.64 Remote Similarity NPC64475
0.6308 Remote Similarity NPC253878
0.6308 Remote Similarity NPC206413
0.6308 Remote Similarity NPC482649
0.6308 Remote Similarity NPC149003
0.6308 Remote Similarity NPC471414
0.6308 Remote Similarity NPC482647
0.6308 Remote Similarity NPC482648
0.6308 Remote Similarity NPC482651
0.6308 Remote Similarity NPC194244
0.6308 Remote Similarity NPC482650
0.6301 Remote Similarity NPC193473
0.6301 Remote Similarity NPC600128
0.6119 Remote Similarity NPC163898
0.6053 Remote Similarity NPC114505
0.6053 Remote Similarity NPC213074
0.5974 Remote Similarity NPC15956
0.5882 Remote Similarity NPC316539
0.5833 Remote Similarity NPC481090
0.5714 Remote Similarity NPC180901
0.5616 Remote Similarity NPC181615
0.56 Remote Similarity NPC79429
0.56 Remote Similarity NPC217635
0.5556 Remote Similarity NPC187616
0.5556 Remote Similarity NPC193026
0.5556 Remote Similarity NPC49603
0.5526 Remote Similarity NPC471667
0.5476 Remote Similarity NPC479449
0.5469 Remote Similarity NPC87725
0.5469 Remote Similarity NPC263261
0.5455 Remote Similarity NPC5851
0.5405 Remote Similarity NPC199539
0.5373 Remote Similarity NPC86030
0.5373 Remote Similarity NPC605857
0.5287 Remote Similarity NPC98624
0.5224 Remote Similarity NPC473408
0.519 Remote Similarity NPC115203
0.5111 Remote Similarity NPC485396
0.5111 Remote Similarity NPC485394
0.5111 Remote Similarity NPC485395

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC54743 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