Natural Product: NPC230013

Natural Product IDNPC230013
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2,4-Dibromo-6-(3,4,6-Tribromo-2-Methoxyphenoxy)Phenol
IUPAC Name 2,4-dibromo-6-(3,4,6-tribromo-2-methoxyphenoxy)phenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL374480
PubChem CID 21637536
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0004155] Diphenylethers
          • [CHEMONTID:0001845] Bromodiphenyl ethers

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 DXFJHCHPUKLLGC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C13H7Br5O3/c1-20-13-10(18)6(15)4-8(17)12(13)21-9-3-5(14)2-7(16)11(9)19/h2-4,19H,1H3
SMILES COc1c(Oc2cc(Br)cc(c2O)Br)c(Br)cc(c1Br)Br

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   605.63 Volume:   323.261
?
Van der Waals volume.
Dense:   1.873 LogP:   4.942
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.416
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.289
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   12.0
TPSA:   38.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.381 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.781 Fsp3:   0.077
MCE-18:   15.0
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.841 Fluc inhibitor:   0.185
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.064
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.457
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.992 Promiscuous compounds:   0.309

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.035 MDCK Permeability:   -4.749
Pgp-inhibitor:   0.796 Pgp-substrate:   0.001
PAMPA:   0.303
?
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):   0.039
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.089
50% Bioavailability (F50%):   0.033

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.868 MRP1:   0.971
Plasma Protein Binding (PPB):   96.982% Volume Distribution (VD):   0.095
Fu: 1.624%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.964
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.134
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.082
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.025
?
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):  3.448 Half-life (T1/2):  2.46

ADMET: Toxicity

hERG Blockers:  0.119 hERG Blockers (10um):  0.711
Human Hepatotoxicity (H-HT):  0.215 Drug-induced Liver Injury (DILI):  0.999
AMES Toxicity:  0.104 Rat Oral Acute Toxicity:  0.896
Maximum Recommended Daily Dose:  0.99 Skin Sensitization:  0.994
Carcinogencity:  0.806 Eye Corrosion:  0.978
Eye Irritation:  0.998 Respiratory Toxicity:  0.515
Drug-induced Neurotoxicity:  0.738 Ototoxicity:  0.06
Hematotoxicity:  0.008 Drug-induced Nephrotoxicity:  0.077
Genotoxicity:  0.989 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.425 Hek293 Cytotoxicity:  0.446
BCF:   2.182
?
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:   5.621
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.366
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.072
?
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
NPO17673 Dysidea herbacea Species n.a. n.a. n.a. n.a. n.a. PMID[10075800]
NPO17673 Dysidea herbacea Species n.a. n.a. n.a. n.a. n.a. PMID[10650102]
NPO8481 Phyllospongia dendyi Species Thorectidae Eukaryota n.a. Palau n.a. PMID[15043436]
NPO4485 Lamellodysidea herbacea Species Dysideidae Eukaryota n.a. Indonesian n.a. PMID[17311456]
NPO17673 Dysidea herbacea Species n.a. n.a. n.a. Mandapam Coast, Tamilnadu, India n.a. PMID[22704923]
NPO4485 Lamellodysidea herbacea Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[28841316]
NPO17673 Dysidea herbacea Species n.a. n.a. n.a. n.a. n.a. PMID[9463111]
NPO13746 Achillea leptophylla Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4485 Lamellodysidea herbacea Species Dysideidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16684 Alibertia macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8481 Phyllospongia dendyi Species Thorectidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4863 Dioscorea futschauensis Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17210 Dorstenia barnimiana Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17673 Dysidea herbacea Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO13985 Oxybasis urbica Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9044 Rubia ustulata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17991 Sedum forsterianum Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16323 Umbilicaria proboscidea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1793 Uvaria mocoli Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7857 Verbascum georgicum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13321 Viguiera cordifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16204 Zieria chevalieri Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4863 Dioscorea futschauensis Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13746 Achillea leptophylla Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13746 Achillea leptophylla Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4863 Dioscorea futschauensis Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16323 Umbilicaria proboscidea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4863 Dioscorea futschauensis Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4863 Dioscorea futschauensis Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16204 Zieria chevalieri Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16684 Alibertia macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17673 Dysidea herbacea Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO4863 Dioscorea futschauensis Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13746 Achillea leptophylla Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13321 Viguiera cordifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1793 Uvaria mocoli Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17210 Dorstenia barnimiana Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9044 Rubia ustulata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13985 Oxybasis urbica Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17991 Sedum forsterianum Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7857 Verbascum georgicum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4485 Lamellodysidea herbacea Species Dysideidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8481 Phyllospongia dendyi Species Thorectidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16323 Umbilicaria proboscidea Species Umbilicariaceae 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
NPT57 Individual protein Induced myeloid leukemia cell differentiation protein Mcl-1 Homo sapiens IC50 > 10.0 ug.mL-1 PMID[19323567]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT79 Organism Bacillus subtilis Bacillus subtilis IZ = 6.0 mm PMID[17311456]
NPT79 Organism Bacillus subtilis Bacillus subtilis IZ = 9.0 mm PMID[17311456]

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 NPC230013 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
0.8182 Intermediate Similarity NPC81149
0.7333 Intermediate Similarity NPC68350
0.7111 Intermediate Similarity NPC170824
0.7021 Intermediate Similarity NPC88733
0.5957 Remote Similarity NPC483504
0.587 Remote Similarity NPC603923
0.5686 Remote Similarity NPC483502
0.5625 Remote Similarity NPC40302
0.5532 Remote Similarity NPC601831
0.5417 Remote Similarity NPC104124
0.54 Remote Similarity NPC63317
0.5208 Remote Similarity NPC196371
0.5102 Remote Similarity NPC44270

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC230013 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
0.5854 Remote Similarity NPD911 Phase 4

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