Natural Product: NPC119786

Natural Product IDNPC119786
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VNVJCGBSMPWVIT-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 324098
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000267] Organohalogen compounds
      • [CHEMONTID:0002866] Aryl halides
        • [CHEMONTID:0001029] Aryl bromides

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 VNVJCGBSMPWVIT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C5H2Br2N2/c6-4-1-3(2-8)9-5(4)7/h1,9H
SMILES c1c(C#N)[nH]c(c1Br)Br

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   247.86 Volume:   136.495
?
Van der Waals volume.
Dense:   1.816 LogP:   2.604
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.34
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.143
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   6.0
TPSA:   39.58
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.754 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.553 Fsp3:   0.0
MCE-18:   6.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.16 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.01
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.425
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.908 Promiscuous compounds:   0.186

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.039 MDCK Permeability:   -4.673
Pgp-inhibitor:   0.814 Pgp-substrate:   0.005
PAMPA:   0.711
?
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):   0.01
20% Bioavailability (F20%):   0.003 30% Bioavailability (F30%):   0.037
50% Bioavailability (F50%):   0.251

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.994 MRP1:   0.235
Plasma Protein Binding (PPB):   94.744% Volume Distribution (VD):   0.23
Fu: 5.005%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.964
OATP1B3 inhibitor:   0.983 BCRP inhibitor:   0.092
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.038 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   0.007 CYP2C19-substrate:   0.987
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.013
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.202
CYP3A4-inhibitor:   0.079 CYP3A4-substrate:   0.61
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.9
HLM stability:   0.227
?
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):  1.579 Half-life (T1/2):  3.254

ADMET: Toxicity

hERG Blockers:  0.105 hERG Blockers (10um):  0.468
Human Hepatotoxicity (H-HT):  0.279 Drug-induced Liver Injury (DILI):  0.963
AMES Toxicity:  0.398 Rat Oral Acute Toxicity:  0.913
Maximum Recommended Daily Dose:  0.96 Skin Sensitization:  0.941
Carcinogencity:  0.717 Eye Corrosion:  1.0
Eye Irritation:  1.0 Respiratory Toxicity:  0.997
Drug-induced Neurotoxicity:  0.687 Ototoxicity:  0.167
Hematotoxicity:  0.027 Drug-induced Nephrotoxicity:  0.078
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.054
A549 Cytotoxicity:  0.032 Hek293 Cytotoxicity:  0.364
BCF:   0.999
?
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:   4.045
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.878
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.419
?
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
NPO27323 Cestrum nocturnum Species Solanaceae Eukaryota leaves n.a. n.a. PMID[11170659]
NPO27012 Laurencia pannosa Species Rhodomelaceae Eukaryota n.a. Malaysian n.a. PMID[11374951]
NPO27323 Cestrum nocturnum Species Solanaceae Eukaryota leaves n.a. n.a. PMID[12502329]
NPO27072 Monochaetum vulcanicum Species Melastomataceae Eukaryota n.a. n.a. n.a. PMID[15165161]
NPO17223 Agelas oroides Species Agelasidae Eukaryota n.a. n.a. n.a. PMID[32072810]
NPO27707 Soja hispida Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20208 Rhinogobius brunneus Species Gobiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27688 Aeonium goochiae Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17223 Agelas oroides Species Agelasidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27740 Alcantara ekmaniana n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO27569 Archangelica officinalis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27725 Artemisia vestita Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26895 Baccharis bigelovii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27648 Cereus aethiops Species Cactaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27191 Schistochila appendiculata Species Schistochilaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27773 Rhododendron ovatum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27072 Monochaetum vulcanicum Species Melastomataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22488 Leptosphaeria oraemaris Species Leptosphaeriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27012 Laurencia pannosa Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7497 Guatteria blepharophylla Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27262 Dryopteris inaequalis Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11140 Coprinopsis cinerea Species Psathyrellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27323 Cestrum nocturnum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16500 Byssochlamys spectabilis Species Thermoascaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27725 Artemisia vestita Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27323 Cestrum nocturnum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27323 Cestrum nocturnum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27773 Rhododendron ovatum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27725 Artemisia vestita Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27725 Artemisia vestita Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27323 Cestrum nocturnum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27725 Artemisia vestita Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27569 Archangelica officinalis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27707 Soja hispida Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17223 Agelas oroides Species Agelasidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27072 Monochaetum vulcanicum Species Melastomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27323 Cestrum nocturnum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27773 Rhododendron ovatum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27262 Dryopteris inaequalis Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27191 Schistochila appendiculata Species Schistochilaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27740 Alcantara ekmaniana n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO7497 Guatteria blepharophylla Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26895 Baccharis bigelovii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11140 Coprinopsis cinerea Species Psathyrellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27012 Laurencia pannosa Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27648 Cereus aethiops Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27688 Aeonium goochiae Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20208 Rhinogobius brunneus Species Gobiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16500 Byssochlamys spectabilis Species Thermoascaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22488 Leptosphaeria oraemaris Species Leptosphaeriaceae 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

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 NPC119786 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
0.5714 Remote Similarity NPC150592
0.5161 Remote Similarity NPC142688

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC119786 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