Natural Product: NPC264379

Natural Product IDNPC264379
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1,2,3-Tribromo-4-(3,5-Dibromo-2-Methoxyphenoxy)-5-Methoxybenzene
IUPAC Name 1,2,3-tribromo-4-(3,5-dibromo-2-methoxyphenoxy)-5-methoxybenzene
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL150603
PubChem CID 21637537
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 MXPHINKLSXPVGO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C14H9Br5O3/c1-20-9-5-7(16)11(18)12(19)14(9)22-10-4-6(15)3-8(17)13(10)21-2/h3-5H,1-2H3
SMILES COc1cc(Br)c(c(c1Oc1cc(Br)cc(c1OC)Br)Br)Br

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   619.65 Volume:   340.557
?
Van der Waals volume.
Dense:   1.82 LogP:   5.089
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.73
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -7.467
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   27.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.334 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.648 Fsp3:   0.143
MCE-18:   15.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.621 Fluc inhibitor:   0.047
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.008
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.774
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.992 Promiscuous compounds:   0.327

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.041 MDCK Permeability:   -4.814
Pgp-inhibitor:   0.971 Pgp-substrate:   0.001
PAMPA:   0.217
?
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):   0.003
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.004
50% Bioavailability (F50%):   0.008

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.99 MRP1:   0.947
Plasma Protein Binding (PPB):   96.958% Volume Distribution (VD):   0.19
Fu: 2.2%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.17
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.931
CYP3A4-inhibitor:   0.933 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.029
?
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):  1.357 Half-life (T1/2):  3.141

ADMET: Toxicity

hERG Blockers:  0.194 hERG Blockers (10um):  0.698
Human Hepatotoxicity (H-HT):  0.251 Drug-induced Liver Injury (DILI):  0.996
AMES Toxicity:  0.166 Rat Oral Acute Toxicity:  0.848
Maximum Recommended Daily Dose:  0.985 Skin Sensitization:  0.969
Carcinogencity:  0.859 Eye Corrosion:  0.984
Eye Irritation:  0.997 Respiratory Toxicity:  0.555
Drug-induced Neurotoxicity:  0.822 Ototoxicity:  0.08
Hematotoxicity:  0.017 Drug-induced Nephrotoxicity:  0.11
Genotoxicity:  0.971 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.33 Hek293 Cytotoxicity:  0.419
BCF:   3.069
?
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:   5.639
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.802
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.672
?
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]
NPO19028 Dysidea granulosa Species n.a. n.a. n.a. n.a. n.a. PMID[25863431]
NPO19028 Dysidea granulosa Species n.a. n.a. n.a. n.a. n.a. PMID[27399938]
NPO40870 Lamellodysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[27399938]
NPO4485 Lamellodysidea herbacea Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[28841316]
NPO19028 Dysidea granulosa Species n.a. n.a. n.a. n.a. n.a. PMID[31990554]
NPO17673 Dysidea herbacea Species n.a. n.a. n.a. n.a. n.a. PMID[9463111]
NPO4863 Dioscorea futschauensis Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16684 Alibertia macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4485 Lamellodysidea herbacea Species Dysideidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8481 Phyllospongia dendyi Species Thorectidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13746 Achillea leptophylla Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40870 Lamellodysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19028 Dysidea granulosa Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO16204 Zieria chevalieri Species Rutaceae 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]
NPO13321 Viguiera cordifolia Species Asteraceae 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]
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]
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[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]
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]
NPO19028 Dysidea granulosa Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO4485 Lamellodysidea herbacea Species Dysideidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7857 Verbascum georgicum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17991 Sedum forsterianum Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16204 Zieria chevalieri Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13985 Oxybasis urbica Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9044 Rubia ustulata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17210 Dorstenia barnimiana Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1793 Uvaria mocoli Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13321 Viguiera cordifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13746 Achillea leptophylla Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4863 Dioscorea futschauensis Species Dioscoreaceae 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]
NPO16684 Alibertia macrophylla Species Rubiaceae 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
NPT41 Individual protein Aldose reductase Homo sapiens Inhibition = 0.0 % PMID[14613323]

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 = 0.0 mm PMID[17311456]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 50.0 ug.mL-1 PMID[27399938]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. MNTD = 50.0 ug ml-1 PMID[27399938]

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 NPC264379 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
0.75 Intermediate Similarity NPC71186
0.7436 Intermediate Similarity NPC221301
0.725 Intermediate Similarity NPC483505
0.7073 Intermediate Similarity NPC483503
0.6905 Remote Similarity NPC483504
0.6364 Remote Similarity NPC483506
0.6042 Remote Similarity NPC173511
0.5833 Remote Similarity NPC88733
0.5833 Remote Similarity NPC197576
0.5682 Remote Similarity NPC162294
0.5532 Remote Similarity NPC163019
0.5532 Remote Similarity NPC1744
0.5319 Remote Similarity NPC37170
0.5306 Remote Similarity NPC131940
0.5217 Remote Similarity NPC235166

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC264379 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