Natural Product: NPC480550

Natural Product IDNPC480550
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GRVFODKSPHRUNC-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 15285577
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 GRVFODKSPHRUNC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H19NO2/c1-3-10(2)15(18)14(17)8-11-9-16-13-7-5-4-6-12(11)13/h4-7,9-10,14,16-17H,3,8H2,1-2H3
SMILES CCC(C)C(=O)C(Cc1c[nH]c2ccccc12)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   245.14 Volume:   266.278
?
Van der Waals volume.
Dense:   0.921 LogP:   2.809
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.799
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.222
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 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:   0.851 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.015 Fsp3:   0.4
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:   0.2 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.041
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.256
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.155 Promiscuous compounds:   0.157

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.157 MDCK Permeability:   -4.803
Pgp-inhibitor:   0.018 Pgp-substrate:   0.148
PAMPA:   0.444
?
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%):   0.009 30% Bioavailability (F30%):   0.095
50% Bioavailability (F50%):   0.68

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.099 MRP1:   0.583
Plasma Protein Binding (PPB):   74.632% Volume Distribution (VD):   0.023
Fu: 18.475%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.243
OATP1B3 inhibitor:   0.988 BCRP inhibitor:   0.125
BSEP inhibitor:   0.966

ADMET: Metabolism

CYP1A2-inhibitor:   0.008 CYP1A2-substrate:   0.24
CYP2C19-inhibitor:   0.018 CYP2C19-substrate:   0.1
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   0.009
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.969
CYP3A4-inhibitor:   0.56 CYP3A4-substrate:   0.129
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.993
HLM stability:   0.961
?
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):  9.537 Half-life (T1/2):  1.283

ADMET: Toxicity

hERG Blockers:  0.113 hERG Blockers (10um):  0.512
Human Hepatotoxicity (H-HT):  0.54 Drug-induced Liver Injury (DILI):  0.147
AMES Toxicity:  0.299 Rat Oral Acute Toxicity:  0.303
Maximum Recommended Daily Dose:  0.543 Skin Sensitization:  0.129
Carcinogencity:  0.422 Eye Corrosion:  0.009
Eye Irritation:  0.669 Respiratory Toxicity:  0.728
Drug-induced Neurotoxicity:  0.49 Ototoxicity:  0.668
Hematotoxicity:  0.301 Drug-induced Nephrotoxicity:  0.385
Genotoxicity:  0.518 RPMI-8226 Immunitoxicity:  0.022
A549 Cytotoxicity:  0.061 Hek293 Cytotoxicity:  0.128
BCF:   0.518
?
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:   3.139
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.4
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.821
?
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
NPT635 Organism Botryotinia fuckeliana Botryotinia fuckeliana MIC = 12.0 ug.mL-1 PMID[7561900]
NPT825 Organism Phytophthora infestans Phytophthora infestans MIC = 100.0 ug.mL-1 PMID[7561900]
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]
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]

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 NPC480550 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 NPC480551
0.5763 Remote Similarity NPC480548
0.5614 Remote Similarity NPC200214
0.5614 Remote Similarity NPC469358
0.56 Remote Similarity NPC230869
0.5574 Remote Similarity NPC605381
0.5517 Remote Similarity NPC480549
0.549 Remote Similarity NPC29886
0.5472 Remote Similarity NPC310665
0.5417 Remote Similarity NPC601214
0.5294 Remote Similarity NPC279081
0.5273 Remote Similarity NPC267343
0.5192 Remote Similarity NPC72435
0.5179 Remote Similarity NPC315555
0.5179 Remote Similarity NPC600736
0.5172 Remote Similarity NPC609424
0.5156 Remote Similarity NPC603162
0.5098 Remote Similarity NPC96102
0.5091 Remote Similarity NPC603879
0.5085 Remote Similarity NPC608269
0.5079 Remote Similarity NPC606619
0.5079 Remote Similarity NPC610347
0.5077 Remote Similarity NPC201700

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC480550 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
0.5185 Remote Similarity NPD786 Pre-clinical
0.5098 Remote Similarity NPD198 Clinical (unspecified phase)

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