Natural Product: NPC293619

Natural Product IDNPC293619
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Bis-(4-Hydroxy-3-Methoxyphenyl)Methane
IUPAC Name 4-[(4-hydroxy-3-methoxyphenyl)methyl]-2-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3746390
PubChem CID 235387
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000369] Diphenylmethanes

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 NTZWJMKBBBBUGE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H16O4/c1-18-14-8-10(3-5-12(14)16)7-11-4-6-13(17)15(9-11)19-2/h3-6,8-9,16-17H,7H2,1-2H3
SMILES COc1cc(ccc1O)Cc1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.1 Volume:   270.225
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Van der Waals volume.
Dense:   0.963 LogP:   2.363
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.482
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.029
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   58.92
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.887 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.825 Fsp3:   0.2
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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.308 Fluc inhibitor:   0.001
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.038
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.306
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.773 Promiscuous compounds:   0.365

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.088 MDCK Permeability:   -4.74
Pgp-inhibitor:   0.034 Pgp-substrate:   0.637
PAMPA:   0.024
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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):   0.0
20% Bioavailability (F20%):   0.282 30% Bioavailability (F30%):   0.139
50% Bioavailability (F50%):   0.776

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.994
Plasma Protein Binding (PPB):   92.956% Volume Distribution (VD):   -0.263
Fu: 7.853%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.055
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.968
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.994
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.862
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.041
?
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):  8.411 Half-life (T1/2):  1.425

ADMET: Toxicity

hERG Blockers:  0.151 hERG Blockers (10um):  0.756
Human Hepatotoxicity (H-HT):  0.468 Drug-induced Liver Injury (DILI):  0.173
AMES Toxicity:  0.47 Rat Oral Acute Toxicity:  0.128
Maximum Recommended Daily Dose:  0.276 Skin Sensitization:  0.932
Carcinogencity:  0.395 Eye Corrosion:  0.785
Eye Irritation:  0.992 Respiratory Toxicity:  0.631
Drug-induced Neurotoxicity:  0.329 Ototoxicity:  0.231
Hematotoxicity:  0.132 Drug-induced Nephrotoxicity:  0.242
Genotoxicity:  0.047 RPMI-8226 Immunitoxicity:  0.091
A549 Cytotoxicity:  0.403 Hek293 Cytotoxicity:  0.492
BCF:   1.241
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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:   3.617
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.459
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.974
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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
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. tuber n.a. PMID[15180301]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[17381154]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[25843525]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO22309 Gastrodia elata Species Orchidaceae 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
NPT466 Cell line U-937 Homo sapiens MNCC = 500.0 uM PMID[28258800]
NPT466 Cell line U-937 Homo sapiens Inhibition = 90.5 % PMID[28258800]
NPT466 Cell line U-937 Homo sapiens Inhibition = 27.5 % PMID[28258800]
NPT466 Cell line U-937 Homo sapiens Inhibition = 98.1 % PMID[28258800]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 11.0 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 28.9 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 43.1 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 7.6 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 15.0 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 72.2 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 3.0 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 33.4 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 49.2 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 7.1 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 26.9 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 4.3 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 62.3 % PMID[26691759]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 95.3 % PMID[26691759]

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 NPC293619 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 NPC7097
0.6364 Remote Similarity NPC156840
0.6 Remote Similarity NPC257124
0.5882 Remote Similarity NPC246358
0.5882 Remote Similarity NPC203719
0.5833 Remote Similarity NPC320987
0.5833 Remote Similarity NPC8547
0.5833 Remote Similarity NPC221049
0.5833 Remote Similarity NPC140359
0.5714 Remote Similarity NPC32163
0.5714 Remote Similarity NPC309203
0.5714 Remote Similarity NPC604189
0.5676 Remote Similarity NPC165133
0.5676 Remote Similarity NPC242885
0.5676 Remote Similarity NPC95614
0.5676 Remote Similarity NPC471693
0.5676 Remote Similarity NPC193544
0.5676 Remote Similarity NPC232316
0.5641 Remote Similarity NPC197757
0.5526 Remote Similarity NPC255675
0.5405 Remote Similarity NPC160380
0.5405 Remote Similarity NPC159418
0.5405 Remote Similarity NPC38996
0.5405 Remote Similarity NPC36108
0.5405 Remote Similarity NPC233731
0.5405 Remote Similarity NPC610203
0.5385 Remote Similarity NPC57490
0.5385 Remote Similarity NPC85488
0.5385 Remote Similarity NPC603326
0.5385 Remote Similarity NPC603989
0.5263 Remote Similarity NPC326599
0.5263 Remote Similarity NPC16651
0.5263 Remote Similarity NPC139519
0.5263 Remote Similarity NPC181969
0.5263 Remote Similarity NPC329595
0.525 Remote Similarity NPC17943
0.525 Remote Similarity NPC299406
0.525 Remote Similarity NPC10932
0.5111 Remote Similarity NPC472091

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC293619 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
0.6 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