Natural Product: NPC474958

Natural Product IDNPC474958
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Eudistalbin A
IUPAC Name 1-(7-bromo-9H-pyrido[3,4-b]indol-1-yl)-3-methylbutan-1-amine
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL490167
PubChem CID 5487489
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001140] Harmala alkaloids

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 PWUUECLZOMPMHQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H18BrN3/c1-9(2)7-13(18)16-15-12(5-6-19-16)11-4-3-10(17)8-14(11)20-15/h3-6,8-9,13,20H,7,18H2,1-2H3
SMILES CC(C)CC(C1=NC=CC2=C1NC3=C2C=CC(=C3)Br)N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   331.07 Volume:   296.078
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Van der Waals volume.
Dense:   1.118 LogP:   4.089
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.586
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.998
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   15.0
TPSA:   54.7
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.741 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.069 Fsp3:   0.312
MCE-18:   34.0
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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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.942 Fluc inhibitor:   0.695
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.448
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.795
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.014 Promiscuous compounds:   0.113

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.9 MDCK Permeability:   -4.745
Pgp-inhibitor:   0.176 Pgp-substrate:   0.047
PAMPA:   0.063
?
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):   0.0
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.041

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.989 MRP1:   0.907
Plasma Protein Binding (PPB):   90.321% Volume Distribution (VD):   0.667
Fu: 8.187%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.873
OATP1B3 inhibitor:   0.93 BCRP inhibitor:   0.022
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.048 CYP1A2-substrate:   0.082
CYP2C19-inhibitor:   0.904 CYP2C19-substrate:   0.044
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.898
CYP2D6-inhibitor:   0.455 CYP2D6-substrate:   0.943
CYP3A4-inhibitor:   0.38 CYP3A4-substrate:   0.158
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.949
HLM stability:   0.019
?
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):  7.249 Half-life (T1/2):  0.322

ADMET: Toxicity

hERG Blockers:  0.409 hERG Blockers (10um):  0.663
Human Hepatotoxicity (H-HT):  0.68 Drug-induced Liver Injury (DILI):  0.635
AMES Toxicity:  0.514 Rat Oral Acute Toxicity:  0.792
Maximum Recommended Daily Dose:  0.883 Skin Sensitization:  0.715
Carcinogencity:  0.652 Eye Corrosion:  0.021
Eye Irritation:  0.872 Respiratory Toxicity:  0.834
Drug-induced Neurotoxicity:  0.827 Ototoxicity:  0.61
Hematotoxicity:  0.502 Drug-induced Nephrotoxicity:  0.682
Genotoxicity:  0.623 RPMI-8226 Immunitoxicity:  0.099
A549 Cytotoxicity:  0.317 Hek293 Cytotoxicity:  0.358
BCF:   1.902
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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:   4.131
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.546
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.043
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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
NPO6291 Eudistoma album Species Polycitoridae Eukaryota n.a. n.a. n.a. PMID[1512602]
NPO6291 Eudistoma album Species Polycitoridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6291 Eudistoma album Species Polycitoridae 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
NPT91 Cell line KB Homo sapiens ED50 = 3.2 ug ml-1 PMID[15974618]
NPT91 Cell line KB Homo sapiens Activity = 100.0 % PMID[15974618]
NPT91 Cell line KB Homo sapiens Activity = 92.0 % PMID[15974618]
NPT91 Cell line KB Homo sapiens Activity = 0.0 % PMID[18302336]
NPT91 Cell line KB Homo sapiens IC50 = 3.2 ug.mL-1 PMID[34332400]
NPT91 Cell line KB Homo sapiens ED50 < 3.2 ug ml-1 PMID[30125723]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 2100.0 nM PMID[30125723]

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 NPC474958 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
0.6393 Remote Similarity NPC237414
0.614 Remote Similarity NPC274229
0.5606 Remote Similarity NPC473761
0.5469 Remote Similarity NPC82331
0.5469 Remote Similarity NPC231536
0.5217 Remote Similarity NPC37152

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474958 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