Natural Product: NPC470505

Natural Product IDNPC470505
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Eudistomin Y13
IUPAC Name (6-bromo-9H-pyrido[3,4-b]indol-1-yl)-phenylmethanol
Synonyms Eudistomin Y13
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2048346
PubChem CID 70690409
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 FUINDJPWTVFMGF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H13BrN2O/c19-12-6-7-15-14(10-12)13-8-9-20-17(16(13)21-15)18(22)11-4-2-1-3-5-11/h1-10,18,21-22H
SMILES Brc1ccc2c(c1)c1ccnc(c1[nH]2)C(c1ccccc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   352.02 Volume:   311.998
?
Van der Waals volume.
Dense:   1.128 LogP:   3.689
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.454
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.064
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   21.0
TPSA:   48.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.555 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.773 Fsp3:   0.056
MCE-18:   40.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.924 Fluc inhibitor:   0.196
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.464
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.356
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.193 Promiscuous compounds:   0.14

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.801 MDCK Permeability:   -4.669
Pgp-inhibitor:   0.036 Pgp-substrate:   0.001
PAMPA:   0.151
?
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%):   0.098
50% Bioavailability (F50%):   0.052

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.955 MRP1:   0.43
Plasma Protein Binding (PPB):   96.713% Volume Distribution (VD):   0.33
Fu: 2.638%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.033
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.724
CYP2C19-inhibitor:   0.017 CYP2C19-substrate:   0.013
CYP2C9-inhibitor:   0.16 CYP2C9-substrate:   0.366
CYP2D6-inhibitor:   0.472 CYP2D6-substrate:   0.398
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   0.117
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.096
?
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):  3.716 Half-life (T1/2):  0.685

ADMET: Toxicity

hERG Blockers:  0.274 hERG Blockers (10um):  0.66
Human Hepatotoxicity (H-HT):  0.485 Drug-induced Liver Injury (DILI):  0.63
AMES Toxicity:  0.478 Rat Oral Acute Toxicity:  0.577
Maximum Recommended Daily Dose:  0.93 Skin Sensitization:  0.194
Carcinogencity:  0.672 Eye Corrosion:  0.001
Eye Irritation:  0.904 Respiratory Toxicity:  0.831
Drug-induced Neurotoxicity:  0.857 Ototoxicity:  0.661
Hematotoxicity:  0.255 Drug-induced Nephrotoxicity:  0.775
Genotoxicity:  0.792 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.165 Hek293 Cytotoxicity:  0.352
BCF:   1.62
?
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:   4.14
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.449
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.999
?
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
NPO33080 synoicum sp. Species Polyclinidae Eukaryota n.a. n.a. n.a. PMID[22652254]
NPO33080 synoicum sp. Species Polyclinidae Eukaryota n.a. n.a. n.a. PMID[23145909]
NPO33080 synoicum sp. Species Polyclinidae Eukaryota n.a. n.a. n.a. PMID[23747224]

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
NPT1821 Individual protein Sortase Staphylococcus aureus IC50 > 283100.0 nM PMID[18579374]
NPT1087 Individual protein Isocitrate lyase Candida albicans IC50 > 283100.0 nM PMID[9514009]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 100.0 ug.mL-1 DOI[10.1016/0960-894X(95)00044-T]
NPT566 Organism Salmonella typhimurium Salmonella enterica subsp. enterica serovar Typhimurium MIC > 100.0 ug.mL-1 PMID[19105653]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 100.0 ug.mL-1 PMID[19307369]
NPT329 Organism Trichophyton rubrum Trichophyton rubrum MIC > 100.0 ug.mL-1 PMID[9548847]
NPT330 Organism Trichophyton mentagrophytes Trichophyton mentagrophytes MIC > 100.0 ug.mL-1 PMID[20055495]
NPT20 Organism Candida albicans Candida albicans MIC > 100.0 ug.mL-1 PMID[22037378]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 100.0 ug.mL-1 PubChem BioAssay data set
NPT766 Organism Proteus vulgaris Proteus vulgaris MIC > 100.0 ug.mL-1 PubChem BioAssay data set
NPT19 Organism Escherichia coli Escherichia coli MIC > 100.0 ug.mL-1 PMID[20738102]
NPT87 Organism Aspergillus fumigatus Aspergillus fumigatus MIC > 100.0 ug.mL-1 PMID[24084296]
NPT2 Others Unspecified n.a. IC50 > 283100.0 nM PMID[12873511]

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 NPC470505 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
0.7458 Intermediate Similarity NPC470503
0.7377 Intermediate Similarity NPC470501
0.6164 Remote Similarity NPC470504
0.6094 Remote Similarity NPC470502
0.6032 Remote Similarity NPC470500
0.6 Remote Similarity NPC603809
0.5469 Remote Similarity NPC97343
0.5373 Remote Similarity NPC279189
0.5147 Remote Similarity NPC26641
0.5143 Remote Similarity NPC162002

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470505 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