Natural Product: NPC471505

Natural Product IDNPC471505
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-[4-(1,3-Benzodioxol-5-Yl)-1-Methoxy-2,3-Dimethylbutyl]-2-Methoxyphenol
IUPAC Name 4-[4-(1,3-benzodioxol-5-yl)-1-methoxy-2,3-dimethylbutyl]-2-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL253432
PubChem CID 44447178
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 GTPIPDMTEBZKCI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H26O5/c1-13(9-15-5-8-18-20(10-15)26-12-25-18)14(2)21(24-4)16-6-7-17(22)19(11-16)23-3/h5-8,10-11,13-14,21-22H,9,12H2,1-4H3
SMILES CC(CC1=CC2=C(C=C1)OCO2)C(C)C(C3=CC(=C(C=C3)O)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   358.18 Volume:   374.235
?
Van der Waals volume.
Dense:   0.957 LogP:   4.216
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.637
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.628
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   16.0
TPSA:   57.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.798 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.394 Fsp3:   0.429
MCE-18:   55.2
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.496 Fluc inhibitor:   0.02
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.016
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.375
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.265 Promiscuous compounds:   0.385

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.963 MDCK Permeability:   -4.761
Pgp-inhibitor:   0.373 Pgp-substrate:   0.016
PAMPA:   0.01
?
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%):   0.014 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.855

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.865 MRP1:   0.963
Plasma Protein Binding (PPB):   97.861% Volume Distribution (VD):   -0.06
Fu: 2.658%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.954
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.142
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.949
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.847
CYP2C9-inhibitor:   0.996 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.999 CYP2C8-inhibitor:   0.85
HLM stability:   0.963
?
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):  5.261 Half-life (T1/2):  0.772

ADMET: Toxicity

hERG Blockers:  0.394 hERG Blockers (10um):  0.776
Human Hepatotoxicity (H-HT):  0.692 Drug-induced Liver Injury (DILI):  0.305
AMES Toxicity:  0.309 Rat Oral Acute Toxicity:  0.181
Maximum Recommended Daily Dose:  0.442 Skin Sensitization:  0.524
Carcinogencity:  0.431 Eye Corrosion:  0.009
Eye Irritation:  0.521 Respiratory Toxicity:  0.452
Drug-induced Neurotoxicity:  0.763 Ototoxicity:  0.661
Hematotoxicity:  0.305 Drug-induced Nephrotoxicity:  0.503
Genotoxicity:  0.022 RPMI-8226 Immunitoxicity:  0.156
A549 Cytotoxicity:  0.382 Hek293 Cytotoxicity:  0.684
BCF:   1.861
?
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:   4.245
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.754
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.979
?
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]
NPO5241 Myristica fragrans Species Myristicaceae 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 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. n.a. Database[HerDing]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
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]
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 = 28.9 % PMID[17998162]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 7900.0 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 NPC471505 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
0.7273 Intermediate Similarity NPC274356
0.7273 Intermediate Similarity NPC101748
0.6897 Remote Similarity NPC142547
0.6897 Remote Similarity NPC228469
0.6557 Remote Similarity NPC487677
0.6557 Remote Similarity NPC487675
0.6557 Remote Similarity NPC46880
0.6406 Remote Similarity NPC487679
0.6406 Remote Similarity NPC487678
0.6349 Remote Similarity NPC106739
0.6271 Remote Similarity NPC165128
0.6129 Remote Similarity NPC88640
0.6129 Remote Similarity NPC101153
0.6129 Remote Similarity NPC193666
0.6129 Remote Similarity NPC123526
0.6129 Remote Similarity NPC608725
0.597 Remote Similarity NPC487682
0.5938 Remote Similarity NPC487681
0.5846 Remote Similarity NPC161249
0.5789 Remote Similarity NPC227217
0.5789 Remote Similarity NPC117780
0.5758 Remote Similarity NPC43514
0.569 Remote Similarity NPC249788
0.5636 Remote Similarity NPC344161
0.5588 Remote Similarity NPC282291
0.5588 Remote Similarity NPC166137
0.5588 Remote Similarity NPC169973
0.5556 Remote Similarity NPC284464
0.55 Remote Similarity NPC11258
0.55 Remote Similarity NPC21867
0.55 Remote Similarity NPC45774
0.55 Remote Similarity NPC74914
0.5472 Remote Similarity NPC80241
0.5472 Remote Similarity NPC301641
0.5472 Remote Similarity NPC485483
0.5439 Remote Similarity NPC142985
0.5397 Remote Similarity NPC135777
0.5362 Remote Similarity NPC265154
0.5357 Remote Similarity NPC282703
0.5357 Remote Similarity NPC184733
0.5357 Remote Similarity NPC128208
0.5357 Remote Similarity NPC129570
0.5357 Remote Similarity NPC63238
0.5357 Remote Similarity NPC602603
0.5246 Remote Similarity NPC485480
0.5156 Remote Similarity NPC28398
0.5147 Remote Similarity NPC67247
0.5091 Remote Similarity NPC165133
0.5091 Remote Similarity NPC242885
0.5091 Remote Similarity NPC95614
0.5091 Remote Similarity NPC232316
0.5077 Remote Similarity NPC488984
0.5077 Remote Similarity NPC488985
0.5067 Remote Similarity NPC304048

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC471505 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