Natural Product: NPC480551

Natural Product IDNPC480551
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AWOMKVFSCPBMJX-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 15285579
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002497] Indoles
          • [CHEMONTID:0004196] 3-alkylindoles

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 AWOMKVFSCPBMJX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C14H17NO2/c1-9(2)14(17)13(16)7-10-8-15-12-6-4-3-5-11(10)12/h3-6,8-9,13,15-16H,7H2,1-2H3
SMILES CC(C)C(=O)C(Cc1c[nH]c2ccccc12)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   231.13 Volume:   248.982
?
Van der Waals volume.
Dense:   0.928 LogP:   2.342
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.374
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.869
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   11.0
TPSA:   53.09
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.848 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.695 Fsp3:   0.357
MCE-18:   24.0
?
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:   0.12 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.043
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.242
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.227 Promiscuous compounds:   0.484

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.247 MDCK Permeability:   -4.859
Pgp-inhibitor:   0.102 Pgp-substrate:   0.015
PAMPA:   0.215
?
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%):   0.034 30% Bioavailability (F30%):   0.186
50% Bioavailability (F50%):   0.871

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.029 MRP1:   0.798
Plasma Protein Binding (PPB):   75.587% Volume Distribution (VD):   0.037
Fu: 24.79%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.807
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.146
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.114 CYP1A2-substrate:   0.342
CYP2C19-inhibitor:   0.154 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.062 CYP2C9-substrate:   0.035
CYP2D6-inhibitor:   0.087 CYP2D6-substrate:   0.967
CYP3A4-inhibitor:   0.918 CYP3A4-substrate:   0.371
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.944
HLM stability:   0.885
?
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):  10.044 Half-life (T1/2):  1.08

ADMET: Toxicity

hERG Blockers:  0.104 hERG Blockers (10um):  0.501
Human Hepatotoxicity (H-HT):  0.522 Drug-induced Liver Injury (DILI):  0.198
AMES Toxicity:  0.33 Rat Oral Acute Toxicity:  0.341
Maximum Recommended Daily Dose:  0.535 Skin Sensitization:  0.126
Carcinogencity:  0.406 Eye Corrosion:  0.011
Eye Irritation:  0.72 Respiratory Toxicity:  0.741
Drug-induced Neurotoxicity:  0.41 Ototoxicity:  0.698
Hematotoxicity:  0.293 Drug-induced Nephrotoxicity:  0.457
Genotoxicity:  0.68 RPMI-8226 Immunitoxicity:  0.019
A549 Cytotoxicity:  0.037 Hek293 Cytotoxicity:  0.108
BCF:   0.463
?
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:   3.093
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.397
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.815
?
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
NPO40794 Bacterial symbiont Species n.a. n.a. n.a. n.a. n.a. PMID[7561900]

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
NPT1264 Organism Burkholderia cepacia Burkholderia cepacia MIC > 80.0 ug.mL-1 PMID[20805026]
NPT1550 Organism Bacillus anthracis Bacillus anthracis MIC > 80.0 ug.mL-1 PMID[20805026]
NPT635 Organism Botryotinia fuckeliana Botryotinia fuckeliana MIC = 12.0 ug.mL-1 PMID[7561900]
NPT825 Organism Phytophthora infestans Phytophthora infestans MIC = 50.0 ug.mL-1 PMID[7561900]
NPT1548 Organism Pseudomonas aeruginosa PAO1 Pseudomonas aeruginosa PAO1 MIC > 80.0 ug.mL-1 PMID[20805026]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC > 80.0 ug.mL-1 PMID[20805026]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC > 80.0 ug.mL-1 PMID[20805026]
NPT87 Organism Aspergillus fumigatus Aspergillus fumigatus MIC > 100.0 ug.mL-1 PMID[7561900]
NPT185 Organism Aspergillus flavus Aspergillus flavus MIC > 100.0 ug.mL-1 PMID[7561900]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans MIC > 100.0 ug.mL-1 PMID[7561900]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC > 80.0 ug.mL-1 PMID[20805026]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 80.0 ug.mL-1 PMID[20805026]
NPT19 Organism Escherichia coli Escherichia coli MIC > 80.0 ug.mL-1 PMID[20805026]
NPT1521 Organism Stenotrophomonas maltophilia Stenotrophomonas maltophilia MIC > 80.0 ug.mL-1 PMID[20805026]
NPT186 Organism Candida tropicalis Candida tropicalis MIC > 100.0 ug.mL-1 PMID[7561900]
NPT2527 Organism Pythium ultimum Pythium ultimum MIC > 100.0 ug.mL-1 PMID[7561900]
NPT747 Organism Acinetobacter baumannii Acinetobacter baumannii MIC > 80.0 ug.mL-1 PMID[20805026]

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 NPC480551 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
0.8511 High Similarity NPC480550
0.6111 Remote Similarity NPC480549
0.5957 Remote Similarity NPC230869
0.5926 Remote Similarity NPC469358
0.5833 Remote Similarity NPC29886
0.58 Remote Similarity NPC310665
0.5778 Remote Similarity NPC601214
0.5636 Remote Similarity NPC200214
0.5625 Remote Similarity NPC279081
0.5577 Remote Similarity NPC267343
0.551 Remote Similarity NPC72435
0.5472 Remote Similarity NPC315555
0.5455 Remote Similarity NPC609424
0.5417 Remote Similarity NPC96102
0.541 Remote Similarity NPC603162
0.5385 Remote Similarity NPC603879
0.5333 Remote Similarity NPC606619
0.5333 Remote Similarity NPC610347
0.5273 Remote Similarity NPC489200
0.5254 Remote Similarity NPC480548
0.5192 Remote Similarity NPC605863
0.5185 Remote Similarity NPC55772
0.5185 Remote Similarity NPC600736
0.5098 Remote Similarity NPC84911
0.5098 Remote Similarity NPC154339
0.5091 Remote Similarity NPC190296
0.5088 Remote Similarity NPC608269
0.5082 Remote Similarity NPC11126
0.5082 Remote Similarity NPC605381
0.5077 Remote Similarity NPC481141

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC480551 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
0.5417 Remote Similarity NPD198 Clinical (unspecified phase)
0.5192 Remote Similarity NPD786 Pre-clinical

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