Natural Product: NPC200553

Natural Product IDNPC200553
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Eudistomin Y3
IUPAC Name (3-bromo-4-hydroxyphenyl)-(9H-pyrido[3,4-b]indol-1-yl)methanone
Synonyms Eudistomin Y3
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2048338
PubChem CID 24800711
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 RVFSIJWZHTVFJY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H11BrN2O2/c19-13-9-10(5-6-15(13)22)18(23)17-16-12(7-8-20-17)11-3-1-2-4-14(11)21-16/h1-9,21-22H
SMILES c1ccc2c(c1)c1ccnc(c1[nH]2)C(=O)c1ccc(c(c1)Br)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   366.0 Volume:   318.151
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Van der Waals volume.
Dense:   1.15 LogP:   3.825
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.204
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.073
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   22.0
TPSA:   65.98
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.516 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.339 Fsp3:   0.0
MCE-18:   21.0
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.93 Fluc inhibitor:   0.619
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.485
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.68
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.217 Promiscuous compounds:   0.41

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.098 MDCK Permeability:   -4.686
Pgp-inhibitor:   0.164 Pgp-substrate:   0.005
PAMPA:   0.489
?
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):   0.001
20% Bioavailability (F20%):   0.01 30% Bioavailability (F30%):   0.062
50% Bioavailability (F50%):   0.387

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.039 MRP1:   0.441
Plasma Protein Binding (PPB):   97.921% Volume Distribution (VD):   0.165
Fu: 1.562%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.585
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.025 CYP1A2-substrate:   0.66
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.938
CYP2C9-inhibitor:   0.016 CYP2C9-substrate:   0.167
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.983
CYP3A4-inhibitor:   0.018 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
HLM stability:   0.854
?
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):  8.323 Half-life (T1/2):  0.927

ADMET: Toxicity

hERG Blockers:  0.393 hERG Blockers (10um):  0.635
Human Hepatotoxicity (H-HT):  0.699 Drug-induced Liver Injury (DILI):  0.966
AMES Toxicity:  0.77 Rat Oral Acute Toxicity:  0.753
Maximum Recommended Daily Dose:  0.933 Skin Sensitization:  0.7
Carcinogencity:  0.752 Eye Corrosion:  0.0
Eye Irritation:  0.959 Respiratory Toxicity:  0.892
Drug-induced Neurotoxicity:  0.835 Ototoxicity:  0.512
Hematotoxicity:  0.32 Drug-induced Nephrotoxicity:  0.833
Genotoxicity:  0.979 RPMI-8226 Immunitoxicity:  0.135
A549 Cytotoxicity:  0.722 Hek293 Cytotoxicity:  0.72
BCF:   1.278
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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:   4.379
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.988
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.799
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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
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 > 272300.0 nM PMID[10560729]
NPT1087 Individual protein Isocitrate lyase Candida albicans IC50 > 272300.0 nM PMID[19908853]

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 = 12.5 ug.mL-1 PMID[19307369]
NPT566 Organism Salmonella typhimurium Salmonella enterica subsp. enterica serovar Typhimurium MIC = 6.25 ug.mL-1 PMID[24273638]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 12.5 ug.mL-1 PubChem BioAssay data set
NPT329 Organism Trichophyton rubrum Trichophyton rubrum MIC > 100.0 ug.mL-1 PMID[25337628]
NPT330 Organism Trichophyton mentagrophytes Trichophyton mentagrophytes MIC > 100.0 ug.mL-1 PMID[20579892]
NPT20 Organism Candida albicans Candida albicans MIC > 100.0 ug.mL-1 PMID[21708464]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 12.5 ug.mL-1 PMID[8411013]
NPT766 Organism Proteus vulgaris Proteus vulgaris MIC = 6.25 ug.mL-1 PMID[19105653]
NPT19 Organism Escherichia coli Escherichia coli MIC = 100.0 ug.mL-1 PMID[8864236]
NPT87 Organism Aspergillus fumigatus Aspergillus fumigatus MIC > 100.0 ug.mL-1 PMID[20405881]
NPT2 Others Unspecified n.a. IC50 = 22500.0 nM PMID[9514009]

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 NPC200553 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
0.8361 Intermediate Similarity NPC174489
0.8095 Intermediate Similarity NPC162002
0.7742 Intermediate Similarity NPC27041
0.6818 Remote Similarity NPC26641
0.6618 Remote Similarity NPC37152
0.6567 Remote Similarity NPC279189
0.5882 Remote Similarity NPC240258
0.5634 Remote Similarity NPC470502
0.5385 Remote Similarity NPC63971
0.5312 Remote Similarity NPC191415
0.5211 Remote Similarity NPC116555
0.52 Remote Similarity NPC470501
0.5156 Remote Similarity NPC102755
0.5139 Remote Similarity NPC470500
0.5139 Remote Similarity NPC205043

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC200553 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