Natural Product: NPC283844

Natural Product IDNPC283844
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2,4-Dihydroxybenzaldehyde
IUPAC Name 2,4-dihydroxybenzaldehyde
Synonyms 2,4-Dihydroxybenzaldehyde; Beta-Resorcylaldehyde
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL243587
PubChem CID 7213
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000124] Aldehydes
            • [CHEMONTID:0003213] Aryl-aldehydes
              • [CHEMONTID:0001345] Benzaldehydes
                • [CHEMONTID:0003978] Hydroxybenzaldehydes

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 IUNJCFABHJZSKB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C7H6O3/c8-4-5-1-2-6(9)3-7(5)10/h1-4,9-10H
SMILES c1cc(cc(c1C=O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   138.03 Volume:   136.897
?
Van der Waals volume.
Dense:   1.008 LogP:   0.559
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.995
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.121
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   7.0
TPSA:   57.53
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.567 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.193 Fsp3:   0.0
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:   0.32 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.01
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.011
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   1.0 Promiscuous compounds:   0.466

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.923 MDCK Permeability:   -4.779
Pgp-inhibitor:   0.183 Pgp-substrate:   0.139
PAMPA:   0.358
?
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):   0.07
20% Bioavailability (F20%):   0.357 30% Bioavailability (F30%):   0.731
50% Bioavailability (F50%):   0.922

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.078 MRP1:   0.478
Plasma Protein Binding (PPB):   72.042% Volume Distribution (VD):   -0.175
Fu: 22.599%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.856
OATP1B3 inhibitor:   0.966 BCRP inhibitor:   0.691
BSEP inhibitor:   0.114

ADMET: Metabolism

CYP1A2-inhibitor:   0.796 CYP1A2-substrate:   0.615
CYP2C19-inhibitor:   0.031 CYP2C19-substrate:   0.14
CYP2C9-inhibitor:   0.931 CYP2C9-substrate:   0.73
CYP2D6-inhibitor:   0.97 CYP2D6-substrate:   0.375
CYP3A4-inhibitor:   0.012 CYP3A4-substrate:   0.161
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.86
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):  4.595 Half-life (T1/2):  1.939

ADMET: Toxicity

hERG Blockers:  0.088 hERG Blockers (10um):  0.602
Human Hepatotoxicity (H-HT):  0.268 Drug-induced Liver Injury (DILI):  0.214
AMES Toxicity:  0.396 Rat Oral Acute Toxicity:  0.274
Maximum Recommended Daily Dose:  0.321 Skin Sensitization:  0.906
Carcinogencity:  0.461 Eye Corrosion:  0.995
Eye Irritation:  1.0 Respiratory Toxicity:  0.835
Drug-induced Neurotoxicity:  0.525 Ototoxicity:  0.121
Hematotoxicity:  0.041 Drug-induced Nephrotoxicity:  0.05
Genotoxicity:  0.56 RPMI-8226 Immunitoxicity:  0.034
A549 Cytotoxicity:  0.211 Hek293 Cytotoxicity:  0.355
BCF:   1.167
?
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:   3.57
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.426
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.001
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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
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11240-011-0014-8]
NPO27689 Mentha pulegium Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[33502110]
NPO27689 Mentha pulegium Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[34328036]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36365393]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36840093]
NPO27689 Mentha pulegium Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[37084277]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[37959863]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38370080]
NPO27689 Mentha pulegium Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38987699]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[39141828]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[39401641]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[39633960]
NPO27689 Mentha pulegium Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[39633960]
NPO27689 Mentha pulegium Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2322 Oryctes nevadensis Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27689 Mentha pulegium Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27689 Mentha pulegium Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27689 Mentha pulegium Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2322 Oryctes nevadensis Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8038 Pachliopta aristolochiae Species Papilionidae 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
NPO27689 Mentha pulegium Oil n.a. 0.45 n.a. n.a. % PMID[39633960]
NPO30828 Mentha piperita Oil n.a. 1.23 n.a. n.a. % PMID[39633960]

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
NPT1418 Individual protein Anandamide amidohydrolase Homo sapiens Inhibition = -13.4 % PMID[19850474]
NPT100 Individual protein Glutaminase kidney isoform, mitochondrial Homo sapiens Potency n.a. 12589.3 nM PubChem BioAssay data set
NPT441 Individual protein Cytochrome P450 19A1 Homo sapiens Activity = 91.7 % PMID[24630560]
NPT43 Individual protein Tyrosinase Agaricus bisporus IC50 > 200000.0 nM PMID[26754613]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 1651.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. IC50 = 4880000.0 nM PMID[17258462]
NPT2 Others Unspecified n.a. IC50 = 108848.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. IC50 = 1400000.0 nM PMID[926120]
NPT2 Others Unspecified n.a. IC50 = 1100000.0 nM PMID[926120]
NPT2 Others Unspecified n.a. FC = 2.6 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. FC = 1.0 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. FC = 10.0 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. FC = 2.5 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. FC = 1.6 n.a. PMID[26986086]
NPT2 Others Unspecified n.a. Activity = 10.0 % PMID[26986086]
NPT2 Others Unspecified n.a. Activity = 2.5 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
- Rattus norvegicus LD50 = 400.0 mg/kg ToxVal
- Mus musculus LD50 = 2.839232863 mg/kg TOXRIC
- Mus musculus LD50 = 1380.0 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 NPC283844 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
0.6154 Remote Similarity NPC303264
0.6071 Remote Similarity NPC161617
0.6071 Remote Similarity NPC600232
0.5769 Remote Similarity NPC230349
0.5769 Remote Similarity NPC219913
0.5484 Remote Similarity NPC95309
0.5455 Remote Similarity NPC184527
0.5357 Remote Similarity NPC163154
0.5357 Remote Similarity NPC80027
0.5161 Remote Similarity NPC78662

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC283844 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