Natural Product: NPC106739

Natural Product IDNPC106739
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-[(1S,2R,3R)-4-(1,3-Benzodioxol-5-Yl)-1-Hydroxy-2,3-Dimethylbutyl]-2-Methoxyphenol
IUPAC Name 4-[(1S,2R,3R)-4-(1,3-benzodioxol-5-yl)-1-hydroxy-2,3-dimethylbutyl]-2-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL253433
PubChem CID 44447179
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001969] Dibenzylbutane lignans

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 GSIZVLCQLAZSSP-IZDJOXEWSA-N
Standard InCHI InChI=1S/C20H24O5/c1-12(8-14-4-7-17-19(9-14)25-11-24-17)13(2)20(22)15-5-6-16(21)18(10-15)23-3/h4-7,9-10,12-13,20-22H,8,11H2,1-3H3/t12-,13-,20+/m1/s1
SMILES COc1cc(ccc1O)[C@H]([C@@H]([C@@H](Cc1ccc2c(c1)OCO2)C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.16 Volume:   356.939
?
Van der Waals volume.
Dense:   0.964 LogP:   3.12
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.903
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.306
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   16.0
TPSA:   68.15
?
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:   0.837 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.303 Fsp3:   0.4
MCE-18:   55.286
?
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:   0.558 Fluc inhibitor:   0.356
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.025
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.059
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.19 Promiscuous compounds:   0.375

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.985 MDCK Permeability:   -4.694
Pgp-inhibitor:   0.063 Pgp-substrate:   0.115
PAMPA:   0.04
?
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):   0.0
20% Bioavailability (F20%):   0.058 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.881

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.243 MRP1:   0.716
Plasma Protein Binding (PPB):   95.921% Volume Distribution (VD):   0.056
Fu: 3.544%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.904
OATP1B3 inhibitor:   0.837 BCRP inhibitor:   0.027
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.01 CYP1A2-substrate:   0.324
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.625
CYP2C9-inhibitor:   0.092 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.958 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.253
HLM stability:   0.856
?
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):  6.757 Half-life (T1/2):  1.538

ADMET: Toxicity

hERG Blockers:  0.165 hERG Blockers (10um):  0.514
Human Hepatotoxicity (H-HT):  0.497 Drug-induced Liver Injury (DILI):  0.274
AMES Toxicity:  0.483 Rat Oral Acute Toxicity:  0.185
Maximum Recommended Daily Dose:  0.568 Skin Sensitization:  0.282
Carcinogencity:  0.543 Eye Corrosion:  0.027
Eye Irritation:  0.874 Respiratory Toxicity:  0.504
Drug-induced Neurotoxicity:  0.434 Ototoxicity:  0.607
Hematotoxicity:  0.249 Drug-induced Nephrotoxicity:  0.471
Genotoxicity:  0.4 RPMI-8226 Immunitoxicity:  0.119
A549 Cytotoxicity:  0.213 Hek293 Cytotoxicity:  0.509
BCF:   0.795
?
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:   3.361
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.788
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.052
?
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
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota seeds n.a. n.a. PMID[17998162]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[1955885]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. fruit n.a. PMID[20879744]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[27419473]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[32515616]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[33444950]
NPO7237 Xanthostemon oppositifolius Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2665 Andinobates fulguritus Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17811 Cephalonoplos segetum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5162 Comaster multifida Species Comatulidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8532 Helipterum tenellum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5334 Rhodotypos scandens Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6113 Piper pedicellosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5746 Pancratium trianthum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO490 Lophozonia menziesii Species Nothofagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28409 Lens phaseoloides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19928 Lachnoanaerobaculum saburreum Species Lachnospiraceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO4539 Ipomoea cristulata Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7393 Esenbeckia nesiotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Leaf Essent. Oil n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Aril n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7237 Xanthostemon oppositifolius Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28409 Lens phaseoloides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8532 Helipterum tenellum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6113 Piper pedicellosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5162 Comaster multifida Species Comatulidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19928 Lachnoanaerobaculum saburreum Species Lachnospiraceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO4539 Ipomoea cristulata Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO490 Lophozonia menziesii Species Nothofagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17811 Cephalonoplos segetum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5746 Pancratium trianthum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7393 Esenbeckia nesiotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5334 Rhodotypos scandens Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2665 Andinobates fulguritus Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5241 Myristica fragrans Species Myristicaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 45.7 % PMID[17998162]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 6300.0 nM PMID[17998162]

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 NPC106739 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
0.8545 High Similarity NPC161249
0.7407 Intermediate Similarity NPC274356
0.7407 Intermediate Similarity NPC101748
0.7358 Intermediate Similarity NPC104077
0.7358 Intermediate Similarity NPC219671
0.7358 Intermediate Similarity NPC147616
0.6949 Remote Similarity NPC487677
0.6949 Remote Similarity NPC487675
0.6667 Remote Similarity NPC46880
0.6349 Remote Similarity NPC471505
0.629 Remote Similarity NPC487681
0.625 Remote Similarity NPC487679
0.625 Remote Similarity NPC487678
0.5902 Remote Similarity NPC474808
0.5902 Remote Similarity NPC474017
0.5893 Remote Similarity NPC227217
0.5893 Remote Similarity NPC117780
0.5789 Remote Similarity NPC249788
0.5741 Remote Similarity NPC344161
0.5672 Remote Similarity NPC169973
0.5645 Remote Similarity NPC284464
0.5577 Remote Similarity NPC80241
0.5577 Remote Similarity NPC301641
0.5577 Remote Similarity NPC485483
0.5538 Remote Similarity NPC474039
0.5441 Remote Similarity NPC282291
0.5441 Remote Similarity NPC166137
0.537 Remote Similarity NPC259742
0.5357 Remote Similarity NPC195292
0.5333 Remote Similarity NPC485480
0.5303 Remote Similarity NPC291101
0.5303 Remote Similarity NPC266197
0.5254 Remote Similarity NPC485482
0.5238 Remote Similarity NPC28398
0.5185 Remote Similarity NPC165133
0.5185 Remote Similarity NPC242885
0.5185 Remote Similarity NPC95614
0.5185 Remote Similarity NPC232316
0.5167 Remote Similarity NPC607444
0.5077 Remote Similarity NPC18576

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC106739 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