Natural Product: NPC307875

Natural Product IDNPC307875
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Syringol
IUPAC Name 2,6-dimethoxyphenol
Synonyms 2,6-Dimethoxy-Phenol; 2,6-Dimethoxyphenol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL109652
PubChem CID 7041
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000134] Phenols
        • [CHEMONTID:0000190] Methoxyphenols

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 KLIDCXVFHGNTTM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C8H10O3/c1-10-6-4-3-5-7(11-2)8(6)9/h3-5,9H,1-2H3
SMILES COc1cccc(c1O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   154.06 Volume:   156.829
?
Van der Waals volume.
Dense:   0.982 LogP:   1.126
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.261
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.353
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   6.0
TPSA:   38.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.699 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.513 Fsp3:   0.25
MCE-18:   6.0
?
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:   Accepted BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.144 Fluc inhibitor:   0.006
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.033
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.024
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.998 Promiscuous compounds:   0.916

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.116 MDCK Permeability:   -4.775
Pgp-inhibitor:   0.624 Pgp-substrate:   0.117
PAMPA:   0.025
?
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):   0.27
20% Bioavailability (F20%):   0.158 30% Bioavailability (F30%):   0.255
50% Bioavailability (F50%):   0.789

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.415 MRP1:   0.735
Plasma Protein Binding (PPB):   85.654% Volume Distribution (VD):   -0.442
Fu: 13.269%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   0.981 BCRP inhibitor:   0.726
BSEP inhibitor:   0.337

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.964
CYP2C9-inhibitor:   0.992 CYP2C9-substrate:   0.075
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.502
CYP3A4-inhibitor:   0.95 CYP3A4-substrate:   0.454
CYP2B6-substrate:   0.532 CYP2C8-inhibitor:   0.989
HLM stability:   0.586
?
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):  4.519 Half-life (T1/2):  2.152

ADMET: Toxicity

hERG Blockers:  0.078 hERG Blockers (10um):  0.522
Human Hepatotoxicity (H-HT):  0.323 Drug-induced Liver Injury (DILI):  0.364
AMES Toxicity:  0.478 Rat Oral Acute Toxicity:  0.262
Maximum Recommended Daily Dose:  0.203 Skin Sensitization:  0.668
Carcinogencity:  0.724 Eye Corrosion:  0.965
Eye Irritation:  0.996 Respiratory Toxicity:  0.796
Drug-induced Neurotoxicity:  0.462 Ototoxicity:  0.185
Hematotoxicity:  0.247 Drug-induced Nephrotoxicity:  0.244
Genotoxicity:  0.059 RPMI-8226 Immunitoxicity:  0.095
A549 Cytotoxicity:  0.144 Hek293 Cytotoxicity:  0.181
BCF:   0.563
?
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:   2.364
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.645
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.902
?
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
NPO28679 Prunus mume Species Rosaceae Eukaryota flowers n.a. n.a. PMID[12193020]
NPO28005 Panax japonicus Species Araliaceae Eukaryota n.a. n.a. n.a. PMID[12350149]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. PMID[21377852]
NPO28005.2 Panax japonicus var. major (burk.) wu et feng Varieties Araliaceae Eukaryota Roots n.a. n.a. PMID[21417387]
NPO28005.2 Panax japonicus var. major (burk.) wu et feng Varieties Araliaceae Eukaryota n.a. root n.a. PMID[21417387]
NPO28679 Prunus mume Species Rosaceae Eukaryota fruits n.a. n.a. PMID[24485782]
NPO28005 Panax japonicus Species Araliaceae Eukaryota Roots n.a. n.a. PMID[28006911]
NPO28005 Panax japonicus Species Araliaceae Eukaryota n.a. n.a. n.a. PMID[28202328]
NPO48692 Quercus ilex subsp. ballota (Desf.) Samp. Genus Fagaceae Eukaryota n.a. n.a. n.a. PMID[36233184]
NPO45380 Handroanthus impetiginosus Species Bignoniaceae Eukaryota n.a. n.a. n.a. PMID[38414225]
NPO31066 Luehea divaricata Species Malvaceae Eukaryota n.a. n.a. n.a. PMID[38414225]
NPO31066 Luehea divaricata Species Malvaceae Eukaryota n.a. leaf n.a. Database[Article]
NPO28005 Panax japonicus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26378 Bistorta manshuriensis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23213 Bistorta officinalis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28005.2 Panax japonicus var. major (burk.) wu et feng Varieties Araliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23213 Bistorta officinalis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28005.2 Panax japonicus var. major (burk.) wu et feng Varieties Araliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28005 Panax japonicus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23213 Bistorta officinalis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26378 Bistorta manshuriensis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28005 Panax japonicus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24093 Drynaria fortunei Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26378 Bistorta manshuriensis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28005 Panax japonicus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28679 Prunus mume Species Rosaceae 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
NPO31066 Luehea divaricata n.a. Leaves 0.69 n.a. n.a. % PMID[38414225]
NPO45380 Handroanthus impetiginosus n.a. Leaves 0.78 n.a. n.a. % PMID[38414225]
NPO48692 Quercus ilex subsp. ballota (Desf.) Samp. n.a. n.a. 1.2235 n.a. n.a. % PMID[36233184]

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
NPT1007 Protein complex GABA-A receptor; alpha-1/beta-2/gamma-2 Homo sapiens EC50 = 100000000.0 nM PMID[12109905]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT137 Cell line L1210 Mus musculus log(1/ID50) = 2.7 n.a. PMID[16279782]
NPT137 Cell line L1210 Mus musculus log(1/ID50) = 3.86 n.a. PMID[16279782]
NPT950 Organism Botryosphaeria dothidea Botryosphaeria dothidea MIC = 5000000.0 nM DOI[10.1016/j.cropro.2012.09.015]
NPT951 Organism Neofusicoccum ribis Neofusicoccum ribis Inhibition = 50.0 % DOI[10.1016/j.cropro.2012.09.015]
NPT951 Organism Neofusicoccum ribis Neofusicoccum ribis MIC = 5000000.0 nM DOI[10.1016/j.cropro.2012.09.015]
NPT693 Organism Xenopus laevis Xenopus laevis EC50 = 100000000.0 nM PMID[12109905]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa Inhibition = 22.3 % DOI[10.6019/CHEMBL4513160]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa Inhibition = 5.23 % DOI[10.6019/CHEMBL4513160]
NPT952 Organism Lasiodiplodia theobromae Lasiodiplodia theobromae Inhibition = 58.0 % DOI[10.1016/j.cropro.2012.09.015]
NPT953 Organism Diplodia seriata Diplodia seriata Inhibition = 58.0 % DOI[10.1016/j.cropro.2012.09.015]
NPT952 Organism Lasiodiplodia theobromae Lasiodiplodia theobromae Inhibition = 57.0 % DOI[10.1016/j.cropro.2012.09.015]
NPT952 Organism Lasiodiplodia theobromae Lasiodiplodia theobromae MIC = 5000000.0 nM DOI[10.1016/j.cropro.2012.09.015]
NPT953 Organism Diplodia seriata Diplodia seriata MIC = 5000000.0 nM DOI[10.1016/j.cropro.2012.09.015]
NPT952 Organism Lasiodiplodia theobromae Lasiodiplodia theobromae GI = 100.0 % DOI[10.1016/j.cropro.2012.09.015]
NPT747 Organism Acinetobacter baumannii Acinetobacter baumannii Inhibition = 16.19 % DOI[10.6019/CHEMBL4513160]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus HD50 = 584.0 uM kg-1 PMID[11606122]





 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
- Rattus norvegicus LD50 = 550.0 mg/kg ToxVal
- Mus musculus LD50 = 2500.0 mg/kg ToxVal

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 NPC307875 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
0.625 Remote Similarity NPC114325
0.5833 Remote Similarity NPC610607
0.5769 Remote Similarity NPC602637
0.5556 Remote Similarity NPC274613
0.5385 Remote Similarity NPC193067
0.5357 Remote Similarity NPC208760

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC307875 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
0.625 Remote Similarity NPD9296 Phase 3

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