Natural Product: NPC235370

Natural Product IDNPC235370
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Ambigol C
IUPAC Name 2,6-dichloro-3,5-bis(2,4-dichlorophenoxy)phenol
Synonyms ambigol C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479906
PubChem CID 5276614
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0004155] Diphenylethers

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 WVDKKFQPVUPWQK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H8Cl6O3/c19-8-1-3-12(10(21)5-8)26-14-7-15(17(24)18(25)16(14)23)27-13-4-2-9(20)6-11(13)22/h1-7,25H
SMILES c1cc(c(cc1Cl)Cl)Oc1cc(c(c(c1Cl)O)Cl)Oc1ccc(cc1Cl)Cl

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   481.86 Volume:   388.124
?
Van der Waals volume.
Dense:   1.242 LogP:   7.096
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.431
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -7.381
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   38.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.401 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.353 Fsp3:   0.0
MCE-18:   20.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.999 Fluc inhibitor:   0.395
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.036
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.03
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.979 Promiscuous compounds:   0.486

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.998 MDCK Permeability:   -4.804
Pgp-inhibitor:   0.459 Pgp-substrate:   0.0
PAMPA:   0.505
?
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):   0.0
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.005
50% Bioavailability (F50%):   0.084

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.97 MRP1:   0.978
Plasma Protein Binding (PPB):   99.694% Volume Distribution (VD):   -0.016
Fu: 0.138%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.958 BCRP inhibitor:   0.095
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.142 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.985 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.748 CYP2D6-substrate:   0.005
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.005 CYP2C8-inhibitor:   1.0
HLM stability:   0.58
?
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):  5.447 Half-life (T1/2):  1.035

ADMET: Toxicity

hERG Blockers:  0.753 hERG Blockers (10um):  0.928
Human Hepatotoxicity (H-HT):  0.674 Drug-induced Liver Injury (DILI):  0.96
AMES Toxicity:  0.17 Rat Oral Acute Toxicity:  0.371
Maximum Recommended Daily Dose:  0.499 Skin Sensitization:  0.921
Carcinogencity:  0.585 Eye Corrosion:  0.06
Eye Irritation:  0.631 Respiratory Toxicity:  0.561
Drug-induced Neurotoxicity:  0.765 Ototoxicity:  0.624
Hematotoxicity:  0.444 Drug-induced Nephrotoxicity:  0.76
Genotoxicity:  0.045 RPMI-8226 Immunitoxicity:  0.041
A549 Cytotoxicity:  0.77 Hek293 Cytotoxicity:  0.896
BCF:   3.021
?
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:   5.331
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.927
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.59
?
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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT839 Cell line L6 Rattus norvegicus MIC = 100.0 ug.mL-1 PMID[15787461]
NPT1231 Organism Microbotryum violaceum Microbotryum violaceum IZ = 5.0 mm PMID[15787461]
NPT844 Organism Trypanosoma brucei rhodesiense Trypanosoma brucei rhodesiense MIC = 11.0 ug.mL-1 PMID[15787461]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 2.498 ug.mL-1 PMID[15787461]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi MIC = 100.0 ug.mL-1 PMID[15787461]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC > 128.0 ug.mL-1 PMID[15787461]
NPT1230 Organism Bacillus megaterium Bacillus megaterium IZ = 7.0 mm PMID[15787461]
NPT485 Organism Plasmodium falciparum (isolate K1 / Thailand) Plasmodium falciparum K1 IC50 = 1.537 ug.mL-1 PMID[15787461]

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 NPC235370 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
0.6774 Remote Similarity NPC319933
0.5897 Remote Similarity NPC86007
0.5897 Remote Similarity NPC205213
0.575 Remote Similarity NPC47769
0.5476 Remote Similarity NPC44270
0.5476 Remote Similarity NPC226737
0.5476 Remote Similarity NPC175520
0.5349 Remote Similarity NPC159866
0.5349 Remote Similarity NPC97157
0.5349 Remote Similarity NPC153580
0.5227 Remote Similarity NPC299939

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC235370 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
0.5897 Remote Similarity NPD915 Phase 4
0.5122 Remote Similarity NPD916 Discontinued

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