Natural Product: NPC216122

Natural Product IDNPC216122
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2,4-Dichlorobenzoic Acid
IUPAC Name 2,4-dichlorobenzoic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1492029
PubChem CID 5787
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0002565] Benzoic acids
            • [CHEMONTID:0002611] Dichlorobenzoic acids

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 ATCRIUVQKHMXSH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C7H4Cl2O2/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3H,(H,10,11)
SMILES Clc1ccc(c(c1)Cl)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   189.96 Volume:   158.529
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Van der Waals volume.
Dense:   1.198 LogP:   2.676
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.9
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.221
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   7.0
TPSA:   37.3
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.74 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.506 Fsp3:   0.0
MCE-18:   7.0
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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:   0.014 Fluc inhibitor:   0.002
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.021
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.997 Promiscuous compounds:   0.624

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.65 MDCK Permeability:   -4.777
Pgp-inhibitor:   0.002 Pgp-substrate:   0.035
PAMPA:   0.979
?
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):   0.001
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.013

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.272 MRP1:   0.985
Plasma Protein Binding (PPB):   98.0% Volume Distribution (VD):   -0.888
Fu: 1.502%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.861
OATP1B3 inhibitor:   0.924 BCRP inhibitor:   0.002
BSEP inhibitor:   0.96

ADMET: Metabolism

CYP1A2-inhibitor:   0.064 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.543 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.016 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.007
HLM stability:   0.001
?
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):  1.581 Half-life (T1/2):  1.554

ADMET: Toxicity

hERG Blockers:  0.11 hERG Blockers (10um):  0.25
Human Hepatotoxicity (H-HT):  0.491 Drug-induced Liver Injury (DILI):  0.813
AMES Toxicity:  0.173 Rat Oral Acute Toxicity:  0.347
Maximum Recommended Daily Dose:  0.117 Skin Sensitization:  0.544
Carcinogencity:  0.405 Eye Corrosion:  0.871
Eye Irritation:  0.99 Respiratory Toxicity:  0.623
Drug-induced Neurotoxicity:  0.624 Ototoxicity:  0.466
Hematotoxicity:  0.483 Drug-induced Nephrotoxicity:  0.705
Genotoxicity:  0.125 RPMI-8226 Immunitoxicity:  0.02
A549 Cytotoxicity:  0.085 Hek293 Cytotoxicity:  0.103
BCF:   -0.139
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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:   2.592
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.724
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.623
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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
NPO14060 Fischerella ambigua Species Hapalosiphonaceae Bacteria n.a. n.a. n.a. PMID[15787461]
NPO12573 Hypericum annulatum Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[17260692]
NPO14060 Fischerella ambigua Species Hapalosiphonaceae Bacteria n.a. n.a. n.a. PMID[19371071]
NPO420 Eucheuma muricatum Species Solieriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14019 Paraphaeosphaeria sporulosa Species Didymosphaeriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14060 Fischerella ambigua Species Hapalosiphonaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO12573 Hypericum annulatum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15556 Vernonia guineensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9797 Aconitum toxicum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO420 Eucheuma muricatum Species Solieriaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15556 Vernonia guineensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12573 Hypericum annulatum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO420 Eucheuma muricatum Species Solieriaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14019 Paraphaeosphaeria sporulosa Species Didymosphaeriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15556 Vernonia guineensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17468 Hortia brasiliensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9797 Aconitum toxicum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12573 Hypericum annulatum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14060 Fischerella ambigua Species Hapalosiphonaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO13801 Artemisia chamaemelifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO420 Eucheuma muricatum Species Solieriaceae 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

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
NPT210 Individual protein Thyroid stimulating hormone receptor Homo sapiens Potency = 100.0 nM PubChem BioAssay data set
NPT277 Individual protein Caspase-1 Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT106 Individual protein Peroxisome proliferator-activated receptor delta Homo sapiens Potency n.a. 3981.1 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 53080.4 nM PubChem BioAssay data set
NPT93 Individual protein Survival motor neuron protein Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency n.a. 78762.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 39474.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 70197 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
- Mus musculus LD50 = 830.0 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 NPC216122 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
0.5862 Remote Similarity NPC324786
0.5161 Remote Similarity NPC291426
0.5161 Remote Similarity NPC602138

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC216122 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