Natural Product: NPC164576

Natural Product IDNPC164576
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-Methoxy-5-Methylphenol
IUPAC Name 3-methoxy-5-methylphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3187650
PubChem CID 76674
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 NOTCZLKDULMKBR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C8H10O2/c1-6-3-7(9)5-8(4-6)10-2/h3-5,9H,1-2H3
SMILES Cc1cc(cc(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   138.07 Volume:   148.039
?
Van der Waals volume.
Dense:   0.933 LogP:   2.144
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.093
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.436
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   6.0
TPSA:   29.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.64 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.777 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:   0 PAINS Alert:   0
Colloidal aggregators:   0.103 Fluc inhibitor:   0.006
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.008
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.999 Promiscuous compounds:   0.537

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.676 MDCK Permeability:   -4.728
Pgp-inhibitor:   0.021 Pgp-substrate:   0.033
PAMPA:   0.074
?
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):   0.002
20% Bioavailability (F20%):   0.058 30% Bioavailability (F30%):   0.068
50% Bioavailability (F50%):   0.668

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.506 MRP1:   0.29
Plasma Protein Binding (PPB):   69.632% Volume Distribution (VD):   0.066
Fu: 28.972%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.245
BSEP inhibitor:   0.17

ADMET: Metabolism

CYP1A2-inhibitor:   0.973 CYP1A2-substrate:   0.97
CYP2C19-inhibitor:   0.61 CYP2C19-substrate:   0.609
CYP2C9-inhibitor:   0.976 CYP2C9-substrate:   0.992
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.819
CYP3A4-inhibitor:   0.063 CYP3A4-substrate:   0.52
CYP2B6-substrate:   0.086 CYP2C8-inhibitor:   0.93
HLM stability:   0.753
?
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):  10.254 Half-life (T1/2):  1.077

ADMET: Toxicity

hERG Blockers:  0.176 hERG Blockers (10um):  0.627
Human Hepatotoxicity (H-HT):  0.481 Drug-induced Liver Injury (DILI):  0.251
AMES Toxicity:  0.488 Rat Oral Acute Toxicity:  0.28
Maximum Recommended Daily Dose:  0.361 Skin Sensitization:  0.689
Carcinogencity:  0.757 Eye Corrosion:  0.985
Eye Irritation:  0.998 Respiratory Toxicity:  0.631
Drug-induced Neurotoxicity:  0.625 Ototoxicity:  0.159
Hematotoxicity:  0.205 Drug-induced Nephrotoxicity:  0.163
Genotoxicity:  0.197 RPMI-8226 Immunitoxicity:  0.057
A549 Cytotoxicity:  0.096 Hek293 Cytotoxicity:  0.237
BCF:   1.059
?
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:   3.088
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.898
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.465
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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
NPO27 Gentiana dahurica Species Gentianaceae Eukaryota n.a. root n.a. PMID[22233034]
NPO18093 Rosa chinensis Species Rosaceae Eukaryota Flowers Muyang, China n.a. PMID[24621197]
NPO40388 Umbilicaria sp. Species Umbilicariaceae Eukaryota n.a. n.a. n.a. PMID[32394716]
NPO4633 Calypogeia integristipula Species Calypogeiaceae Eukaryota n.a. n.a. n.a. PMID[37959695]
NPO54488 Mentha vagans Genus Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38923285]
NPO3729 Cetraria islandica Species Parmeliaceae Eukaryota n.a. n.a. n.a. PMID[7561895]
NPO4633 Calypogeia integristipula Species Calypogeiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25424 Putterlickia verrucosa Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18093 Rosa chinensis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3729 Cetraria islandica Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2777 Cirsium brevistylum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5786 Desmodium oxyphyllum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27 Gentiana dahurica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6513 Vernonia condensata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40388 Umbilicaria sp. Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18093 Rosa chinensis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27 Gentiana dahurica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27 Gentiana dahurica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25424 Putterlickia verrucosa Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18093 Rosa chinensis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27 Gentiana dahurica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18093 Rosa chinensis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27 Gentiana dahurica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18093 Rosa chinensis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25424 Putterlickia verrucosa Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5786 Desmodium oxyphyllum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2777 Cirsium brevistylum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27 Gentiana dahurica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4633 Calypogeia integristipula Species Calypogeiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3729 Cetraria islandica Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6513 Vernonia condensata Species Asteraceae 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
NPO54488 Mentha vagans Oil n.a. 1.26 n.a. n.a. % PMID[38923285]

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
NPT153 Individual protein Androgen Receptor Homo sapiens Potency n.a. 30899.4 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT81 Cell line A549 Homo sapiens IC50 > 40000.0 nM PMID[32394716]
NPT83 Cell line MCF7 Homo sapiens IC50 > 40000.0 nM PMID[32394716]
NPT91 Cell line KB Homo sapiens IC50 > 40000.0 nM PMID[32394716]
NPT2 Others Unspecified n.a. Potency n.a. 24547.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 54482.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 10963.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 21875.1 nM PubChem BioAssay data set

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 NPC164576 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
0.6111 Remote Similarity NPC298134
0.5946 Remote Similarity NPC216836
0.5484 Remote Similarity NPC255068
0.5405 Remote Similarity NPC276737
0.5405 Remote Similarity NPC168657
0.5405 Remote Similarity NPC141090
0.5405 Remote Similarity NPC280606
0.5405 Remote Similarity NPC94045
0.5357 Remote Similarity NPC602758
0.5263 Remote Similarity NPC22610
0.525 Remote Similarity NPC220106
0.525 Remote Similarity NPC28765
0.5128 Remote Similarity NPC53906
0.5128 Remote Similarity NPC226629

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC164576 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