Natural Product: NPC490874

Natural Product IDNPC490874
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 methylparaben
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001350] Benzoic acid esters
            • [CHEMONTID:0004701] p-Hydroxybenzoic acid esters
              • [CHEMONTID:0004702] p-Hydroxybenzoic acid alkyl esters

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 LXCFILQKKLGQFO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C8H8O3/c1-11-8(10)6-2-4-7(9)5-3-6/h2-5,9H,1H3
SMILES COC(=O)C1=CC=C(C=C1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   152.05 Volume:   154.193
?
Van der Waals volume.
Dense:   0.986 LogP:   2.005
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.97
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.576
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   7.0
TPSA:   46.53
?
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:   0.614 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.387 Fsp3:   0.125
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:   0.057 Fluc inhibitor:   0.3
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.013
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.012
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.999 Promiscuous compounds:   0.959

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.452 MDCK Permeability:   -4.463
Pgp-inhibitor:   0.268 Pgp-substrate:   0.193
PAMPA:   0.283
?
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):   0.006
20% Bioavailability (F20%):   0.318 30% Bioavailability (F30%):   0.419
50% Bioavailability (F50%):   0.888

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.032 MRP1:   0.961
Plasma Protein Binding (PPB):   92.783% Volume Distribution (VD):   -0.041
Fu: 8.056%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.829
OATP1B3 inhibitor:   0.954 BCRP inhibitor:   0.874
BSEP inhibitor:   0.695

ADMET: Metabolism

CYP1A2-inhibitor:   0.171 CYP1A2-substrate:   0.76
CYP2C19-inhibitor:   0.017 CYP2C19-substrate:   0.208
CYP2C9-inhibitor:   0.309 CYP2C9-substrate:   0.237
CYP2D6-inhibitor:   0.864 CYP2D6-substrate:   0.572
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.498
CYP2B6-substrate:   0.006 CYP2C8-inhibitor:   0.94
HLM stability:   0.973
?
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):  11.25 Half-life (T1/2):  1.069

ADMET: Toxicity

hERG Blockers:  0.105 hERG Blockers (10um):  0.618
Human Hepatotoxicity (H-HT):  0.139 Drug-induced Liver Injury (DILI):  0.263
AMES Toxicity:  0.3 Rat Oral Acute Toxicity:  0.188
Maximum Recommended Daily Dose:  0.19 Skin Sensitization:  0.577
Carcinogencity:  0.641 Eye Corrosion:  0.715
Eye Irritation:  0.997 Respiratory Toxicity:  0.296
Drug-induced Neurotoxicity:  0.461 Ototoxicity:  0.117
Hematotoxicity:  0.045 Drug-induced Nephrotoxicity:  0.072
Genotoxicity:  0.092 RPMI-8226 Immunitoxicity:  0.033
A549 Cytotoxicity:  0.041 Hek293 Cytotoxicity:  0.31
BCF:   0.936
?
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:   3.186
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.011
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.597
?
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
NPO41986 A new engineered strain of Saccharomyces cerevisiae INVSc1 [tHMG1, IDI1, ERG20, ERG9] Strain Saccharomycetaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.ces.2016.06.014]

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
NPT262 Individual protein Muscarinic acetylcholine receptor M1 Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT228 Individual protein Norepinephrine transporter Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT242 Individual protein Dopamine D1 receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT2769 Individual protein Thromboxane A2 receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT261 Individual protein Monoamine oxidase A Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT145 Individual protein Mu opioid receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT30 Individual protein Cyclooxygenase-1 Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT1788 Individual protein Alpha-1a adrenergic receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT153 Individual protein Androgen Receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT204 Individual protein Acetylcholinesterase Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT1478 Individual protein Vascular endothelial growth factor receptor 2 Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT222 Individual protein Alpha-2a adrenergic receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT295 Individual protein Serotonin transporter Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT30 Individual protein Cyclooxygenase-1 Homo sapiens AC50 > 1000.0 nM PMID[37468498]
NPT291 Individual protein Serotonin 2b (5-HT2b) receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT2761 Individual protein Phosphodiesterase 4A Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT218 Individual protein Adenosine A3 receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT263 Individual protein Muscarinic acetylcholine receptor M2 Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT108 Individual protein Estrogen receptor alpha Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT244 Individual protein Dopamine D3 receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT246 Individual protein Dopamine transporter Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT987 Individual protein Histamine H3 receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 11.4 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT98 Individual protein HERG Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT542 Individual protein Progesterone receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 16.32 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT5104 Individual protein Phosphodiesterase 3A Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT92 Individual protein Serotonin 1a (5-HT1a) receptor Homo sapiens AC50 > 30000.0 nM PMID[37468498]
NPT670 Individual protein Thrombin Homo sapiens AC50 > 30000.0 nM PMID[37468498]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29392 Protein complex Gamma-aminobutyric acid receptor subunit alpha-1/alpha-2/beta-2/gamma-2 Homo sapiens AC50 > 30000.0 nM PMID[37468498]

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 NPC490874 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
1.0 High Similarity NPC131192
0.6897 Remote Similarity NPC27633
0.6552 Remote Similarity NPC158654
0.6333 Remote Similarity NPC81808
0.625 Remote Similarity NPC203925
0.625 Remote Similarity NPC94298
0.5806 Remote Similarity NPC95309
0.5588 Remote Similarity NPC159418
0.5556 Remote Similarity NPC130398
0.5484 Remote Similarity NPC94810
0.5429 Remote Similarity NPC326065
0.5405 Remote Similarity NPC607895
0.5333 Remote Similarity NPC264145
0.5172 Remote Similarity NPC188895
0.5128 Remote Similarity NPC602228
0.5122 Remote Similarity NPC114116

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC490874 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
0.6897 Remote Similarity NPD9545 Pre-clinical
0.5758 Remote Similarity NPD9509 Clinical (unspecified phase)

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