Natural Product: NPC37170

Natural Product IDNPC37170
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KMQWWGLIGSFYAT-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11455391
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 KMQWWGLIGSFYAT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C13H8Br4O3/c1-19-13-9(17)3-7(15)5-11(13)20-12-8(16)2-6(14)4-10(12)18/h2-5,18H,1H3
SMILES COc1c(cc(cc1Oc1c(cc(cc1O)Br)Br)Br)Br

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   527.72 Volume:   303.978
?
Van der Waals volume.
Dense:   1.736 LogP:   4.808
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.478
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.045
?
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:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.509 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.567 Fsp3:   0.077
MCE-18:   14.0
?
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:   0.942 Fluc inhibitor:   0.06
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.571
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.988 Promiscuous compounds:   0.328

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.055 MDCK Permeability:   -4.755
Pgp-inhibitor:   0.895 Pgp-substrate:   0.005
PAMPA:   0.071
?
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):   0.013
20% Bioavailability (F20%):   0.005 30% Bioavailability (F30%):   0.061
50% Bioavailability (F50%):   0.011

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.877 MRP1:   0.975
Plasma Protein Binding (PPB):   96.724% Volume Distribution (VD):   0.064
Fu: 2.348%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.96
OATP1B3 inhibitor:   0.976 BCRP inhibitor:   0.132
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.163
CYP3A4-inhibitor:   0.494 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.024
?
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):  5.431 Half-life (T1/2):  1.74

ADMET: Toxicity

hERG Blockers:  0.127 hERG Blockers (10um):  0.732
Human Hepatotoxicity (H-HT):  0.224 Drug-induced Liver Injury (DILI):  0.979
AMES Toxicity:  0.162 Rat Oral Acute Toxicity:  0.752
Maximum Recommended Daily Dose:  0.954 Skin Sensitization:  0.978
Carcinogencity:  0.782 Eye Corrosion:  0.949
Eye Irritation:  0.998 Respiratory Toxicity:  0.539
Drug-induced Neurotoxicity:  0.729 Ototoxicity:  0.101
Hematotoxicity:  0.041 Drug-induced Nephrotoxicity:  0.107
Genotoxicity:  0.915 RPMI-8226 Immunitoxicity:  0.057
A549 Cytotoxicity:  0.214 Hek293 Cytotoxicity:  0.34
BCF:   2.48
?
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:   5.509
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.297
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.991
?
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]
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]
NPO17673 Dysidea herbacea Species n.a. n.a. n.a. Mandapam Coast, Tamilnadu, India n.a. PMID[22704923]
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]
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]
NPO17673 Dysidea herbacea Species n.a. n.a. n.a. n.a. n.a. PMID[9463111]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[9748373]
NPO16684 Alibertia macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13746 Achillea leptophylla Species Asteraceae 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]
NPO16323 Umbilicaria proboscidea Species Umbilicariaceae 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]
NPO16204 Zieria chevalieri Species Rutaceae 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]

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
NPT3681 Organism Aspergillus Aspergillus MIC = 1.95 ug.mL-1 PMID[27936443]

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 NPC37170 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 NPC173511
0.7045 Intermediate Similarity NPC131940
0.6522 Remote Similarity NPC197576
0.5909 Remote Similarity NPC483503
0.5814 Remote Similarity NPC221301
0.5778 Remote Similarity NPC483504
0.5682 Remote Similarity NPC162294
0.5682 Remote Similarity NPC483505
0.5556 Remote Similarity NPC71186
0.5556 Remote Similarity NPC104124
0.5319 Remote Similarity NPC264379
0.5319 Remote Similarity NPC483506
0.5227 Remote Similarity NPC86007
0.5111 Remote Similarity NPC41232

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC37170 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