Natural Product: NPC63317

Natural Product IDNPC63317
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3,4,5-Tribromo-2-(3,5-Dibromo-2-Hydroxyphenoxy)Phenol
IUPAC Name 3,4,5-tribromo-2-(3,5-dibromo-2-hydroxyphenoxy)phenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL149159
PubChem CID 11801671
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 WMMMSBGZKIDZDQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H5Br5O3/c13-4-1-6(15)11(19)8(2-4)20-12-7(18)3-5(14)9(16)10(12)17/h1-3,18-19H
SMILES Brc1cc(Oc2c(O)cc(c(c2Br)Br)Br)c(c(c1)Br)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   591.62 Volume:   305.965
?
Van der Waals volume.
Dense:   1.934 LogP:   4.992
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.055
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.658
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   12.0
TPSA:   49.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.38 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.849 Fsp3:   0.0
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:   0.93 Fluc inhibitor:   0.34
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.296
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.998 Promiscuous compounds:   0.392

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.03 MDCK Permeability:   -4.62
Pgp-inhibitor:   0.276 Pgp-substrate:   0.001
PAMPA:   0.791
?
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):   0.049
20% Bioavailability (F20%):   0.006 30% Bioavailability (F30%):   0.058
50% Bioavailability (F50%):   0.046

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.448 MRP1:   0.958
Plasma Protein Binding (PPB):   96.445% Volume Distribution (VD):   -0.087
Fu: 2.83%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.972
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.143
BSEP inhibitor:   0.996

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:   0.062
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.084
?
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):  3.103 Half-life (T1/2):  2.718

ADMET: Toxicity

hERG Blockers:  0.127 hERG Blockers (10um):  0.69
Human Hepatotoxicity (H-HT):  0.212 Drug-induced Liver Injury (DILI):  0.997
AMES Toxicity:  0.115 Rat Oral Acute Toxicity:  0.894
Maximum Recommended Daily Dose:  0.993 Skin Sensitization:  0.986
Carcinogencity:  0.795 Eye Corrosion:  0.992
Eye Irritation:  0.999 Respiratory Toxicity:  0.513
Drug-induced Neurotoxicity:  0.583 Ototoxicity:  0.064
Hematotoxicity:  0.009 Drug-induced Nephrotoxicity:  0.069
Genotoxicity:  0.997 RPMI-8226 Immunitoxicity:  0.06
A549 Cytotoxicity:  0.537 Hek293 Cytotoxicity:  0.414
BCF:   1.673
?
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:   5.801
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.32
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.249
?
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
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[11374954]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[15921404]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[1593283]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[18198840]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. at 1020 m depth from Chuuk Atoll, Federated States of Micronesia n.a. PMID[18824352]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[20230038]
NPO19028 Dysidea granulosa Species n.a. n.a. n.a. n.a. n.a. PMID[25863431]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[26551342]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[26863083]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[27336796]
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]
NPO19028 Dysidea granulosa Species n.a. n.a. n.a. n.a. n.a. PMID[31990554]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[32243140]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. Indo-Pacific n.a. PMID[7494145]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[9748373]
NPO19028 Dysidea granulosa Species n.a. n.a. 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[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
NPT2784 Individual protein GMP synthase [glutamine-hydrolyzing] Homo sapiens Inhibition = 89.0 % PMID[19124250]
NPT41 Individual protein Aldose reductase Homo sapiens Inhibition = 0.0 % PMID[26331426]
NPT57 Individual protein Induced myeloid leukemia cell differentiation protein Mcl-1 Homo sapiens IC50 > 10.0 ug.mL-1 PMID[20606071]

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 = 7.0 mm DrugMatrix in vitro pharmacology data
NPT79 Organism Bacillus subtilis Bacillus subtilis IZ = 10.0 mm PMID[16472241]
NPT79 Organism Bacillus subtilis Bacillus subtilis IZ = 13.0 mm PMID[18278869]
NPT79 Organism Bacillus subtilis Bacillus subtilis IZ = 16.0 mm PMID[9868159]
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 NPC63317 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
0.6905 Remote Similarity NPC104124
0.6744 Remote Similarity NPC137922
0.6667 Remote Similarity NPC603923
0.6364 Remote Similarity NPC40302
0.6047 Remote Similarity NPC41232
0.5909 Remote Similarity NPC196371
0.5909 Remote Similarity NPC601831
0.5778 Remote Similarity NPC474375
0.5714 Remote Similarity NPC88733
0.56 Remote Similarity NPC173511
0.5532 Remote Similarity NPC299939
0.54 Remote Similarity NPC230013
0.54 Remote Similarity NPC483502
0.54 Remote Similarity NPC81149
0.5306 Remote Similarity NPC68350
0.5106 Remote Similarity NPC44270
0.5102 Remote Similarity NPC64130

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC63317 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
0.6316 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