Natural Product: NPC78662

Natural Product IDNPC78662
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-Hydroxy-4-Methoxybenzaldehyde
IUPAC Name 2-hydroxy-4-methoxybenzaldehyde
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL350966
PubChem CID 69600
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 WZUODJNEIXSNEU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C8H8O3/c1-11-7-3-2-6(5-9)8(10)4-7/h2-5,10H,1H3
SMILES COc1ccc(C=O)c(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   152.05 Volume:   154.193
?
Van der Waals volume.
Dense:   0.986 LogP:   1.71
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.814
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.672
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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:   0.648 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.951 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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.268 Fluc inhibitor:   0.008
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.186
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.999 Promiscuous compounds:   0.384

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.799 MDCK Permeability:   -4.75
Pgp-inhibitor:   0.541 Pgp-substrate:   0.003
PAMPA:   0.075
?
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):   0.435
20% Bioavailability (F20%):   0.448 30% Bioavailability (F30%):   0.83
50% Bioavailability (F50%):   0.753

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.048 MRP1:   0.008
Plasma Protein Binding (PPB):   77.762% Volume Distribution (VD):   -0.212
Fu: 19.701%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.98
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.522
BSEP inhibitor:   0.926

ADMET: Metabolism

CYP1A2-inhibitor:   0.917 CYP1A2-substrate:   0.654
CYP2C19-inhibitor:   0.252 CYP2C19-substrate:   0.082
CYP2C9-inhibitor:   0.902 CYP2C9-substrate:   0.277
CYP2D6-inhibitor:   0.789 CYP2D6-substrate:   0.055
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.003
CYP2B6-substrate:   0.025 CYP2C8-inhibitor:   0.586
HLM stability:   0.569
?
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):  9.426 Half-life (T1/2):  1.592

ADMET: Toxicity

hERG Blockers:  0.096 hERG Blockers (10um):  0.525
Human Hepatotoxicity (H-HT):  0.347 Drug-induced Liver Injury (DILI):  0.378
AMES Toxicity:  0.506 Rat Oral Acute Toxicity:  0.249
Maximum Recommended Daily Dose:  0.266 Skin Sensitization:  0.761
Carcinogencity:  0.61 Eye Corrosion:  0.99
Eye Irritation:  0.999 Respiratory Toxicity:  0.82
Drug-induced Neurotoxicity:  0.563 Ototoxicity:  0.134
Hematotoxicity:  0.139 Drug-induced Nephrotoxicity:  0.151
Genotoxicity:  0.174 RPMI-8226 Immunitoxicity:  0.057
A549 Cytotoxicity:  0.116 Hek293 Cytotoxicity:  0.204
BCF:   1.194
?
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:   3.653
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.75
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.417
?
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
NPO29276 Juglans nigra Species Juglandaceae Eukaryota n.a. xylem n.a. PMID[14727919]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota n.a. bark n.a. PMID[14727919]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota n.a. leaf n.a. PMID[14727919]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota n.a. root n.a. PMID[14727919]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[28294615]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20248 Bupleurum marginatum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9465 Stelmatocrypton khasianum n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota Pericarp n.a. n.a. Database[FooDB]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota Essential Oil n.a. n.a. Database[FooDB]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota n.a. n.a. Database[FooDB]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20248.1 Bupleurum marginatum var. stenophyllum Varieties Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9465 Stelmatocrypton khasianum n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20248 Bupleurum marginatum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20248.1 Bupleurum marginatum var. stenophyllum Varieties Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9465 Stelmatocrypton khasianum n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20248 Bupleurum marginatum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9465 Stelmatocrypton khasianum n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29276 Juglans nigra Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20248 Bupleurum marginatum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29276 Juglans nigra Species Juglandaceae 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
NPO29276 Juglans nigra Other (raw) Essential Oil 2400 2400 2400 mg/100g Database [DUKE]

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
NPT741 Individual protein Tyrosinase Homo sapiens IC50 = 30000.0 nM PMID[14741268]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. MIC > 33000.0 nM PMID[17507232]
NPT2 Others Unspecified n.a. IC50 = 2000000.0 nM PMID[17258462]
NPT2 Others Unspecified n.a. FC = 9.8 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. FC = 3.2 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. FC = 10.0 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. FC = 3.75 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. FC = 2.0 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. Activity = 40.0 % PMID[26986086]
NPT2 Others Unspecified n.a. Activity = 10.0 % PMID[26986086]
NPT2 Others Unspecified n.a. FC = 8.8 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. FC = 1.5 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. Activity = 22.0 ug PMID[26986086]
NPT2 Others Unspecified n.a. Activity = 3.5 ug PMID[26986086]

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 NPC78662 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 NPC186098
0.6061 Remote Similarity NPC42292
0.5484 Remote Similarity NPC237330
0.5484 Remote Similarity NPC128428
0.5455 Remote Similarity NPC600835
0.5405 Remote Similarity NPC599885
0.5357 Remote Similarity NPC57879
0.5161 Remote Similarity NPC283844
0.5152 Remote Similarity NPC117237
0.5128 Remote Similarity NPC479032
0.5122 Remote Similarity NPC229147

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC78662 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
0.5405 Remote Similarity NPD1240 Phase 4
0.5405 Remote Similarity NPD1607 Phase 4
0.5152 Remote Similarity NPD9494 Approved

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