Natural Product: NPC605381

Natural Product IDNPC605381
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NIQUZFQMNMNAMD-NSHDSACASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL487932
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 NIQUZFQMNMNAMD-NSHDSACASA-N
Standard InCHI InChI=1S/C16H20N2O2/c1-3-11(2)15(19)16(20)17-9-8-12-10-18-14-7-5-4-6-13(12)14/h4-7,10-11,18H,3,8-9H2,1-2H3,(H,17,20)/t11-/m0/s1
SMILES CC[C@H](C)C(=O)C(=O)NCCc1c[nH]c2ccccc12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.15 Volume:   291.935
?
Van der Waals volume.
Dense:   0.932 LogP:   2.725
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.85
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.346
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   12.0
TPSA:   61.96
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.793 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.575 Fsp3:   0.375
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.351 Fluc inhibitor:   0.418
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.058
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.434
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.574

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.856 MDCK Permeability:   -4.499
Pgp-inhibitor:   0.913 Pgp-substrate:   0.645
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):   0.187
20% Bioavailability (F20%):   0.452 30% Bioavailability (F30%):   0.781
50% Bioavailability (F50%):   0.889

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.434 MRP1:   0.156
Plasma Protein Binding (PPB):   90.893% Volume Distribution (VD):   0.119
Fu: 8.8%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.709
OATP1B3 inhibitor:   0.738 BCRP inhibitor:   0.452
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.017 CYP1A2-substrate:   0.047
CYP2C19-inhibitor:   0.549 CYP2C19-substrate:   0.097
CYP2C9-inhibitor:   0.575 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.006 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.744 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.04 CYP2C8-inhibitor:   0.962
HLM stability:   0.404
?
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):  8.525 Half-life (T1/2):  0.555

ADMET: Toxicity

hERG Blockers:  0.183 hERG Blockers (10um):  0.39
Human Hepatotoxicity (H-HT):  0.447 Drug-induced Liver Injury (DILI):  0.418
AMES Toxicity:  0.308 Rat Oral Acute Toxicity:  0.348
Maximum Recommended Daily Dose:  0.579 Skin Sensitization:  0.883
Carcinogencity:  0.239 Eye Corrosion:  0.002
Eye Irritation:  0.7 Respiratory Toxicity:  0.775
Drug-induced Neurotoxicity:  0.703 Ototoxicity:  0.416
Hematotoxicity:  0.453 Drug-induced Nephrotoxicity:  0.457
Genotoxicity:  0.971 RPMI-8226 Immunitoxicity:  0.011
A549 Cytotoxicity:  0.047 Hek293 Cytotoxicity:  0.118
BCF:   1.234
?
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:   3.566
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.806
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.484
?
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
NPO9556 Annona atemoya Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO54520 Xenorhabdus nematophilus Genus Morganellaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO9556 Annona atemoya Species Annonaceae 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
NPT331 Organism Ralstonia solanacearum Ralstonia solanacearum Activity n.a. n.a. n.a. PMID[18491867]
NPT2920 Organism Pseudomonas syringae Pseudomonas syringae Activity n.a. n.a. n.a. PMID[18491867]
NPT1499 Organism Erwinia amylovora Erwinia amylovora Activity n.a. n.a. n.a. PMID[18491867]
NPT29268 Organism Mammaliicoccus lentus Mammaliicoccus lentus Activity n.a. n.a. n.a. PMID[18491867]
NPT3534 Organism Xanthomonas campestris Xanthomonas campestris Activity n.a. n.a. n.a. PMID[18491867]
NPT79 Organism Bacillus subtilis Bacillus subtilis Activity n.a. n.a. n.a. PMID[18491867]
NPT29084 Organism Nakaseomyces glabratus Nakaseomyces glabratus Activity n.a. n.a. n.a. PMID[18491867]
NPT176 Organism Artemia salina Artemia salina IC50 = 50.0 ug.mL-1 PMID[18491867]
NPT19 Organism Escherichia coli Escherichia coli Activity n.a. n.a. n.a. PMID[18491867]
NPT1209 Organism Pseudomonas fluorescens Pseudomonas fluorescens Activity n.a. n.a. n.a. PMID[18491867]

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 NPC605381 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
0.7407 Intermediate Similarity NPC608269
0.678 Remote Similarity NPC469760
0.678 Remote Similarity NPC469786
0.6333 Remote Similarity NPC476460
0.6094 Remote Similarity NPC469762
0.5574 Remote Similarity NPC480550
0.5538 Remote Similarity NPC611116
0.5312 Remote Similarity NPC480548
0.5303 Remote Similarity NPC474561
0.5263 Remote Similarity NPC310665
0.5161 Remote Similarity NPC602373
0.5152 Remote Similarity NPC11126
0.5082 Remote Similarity NPC480551
0.5079 Remote Similarity NPC314002
0.5079 Remote Similarity NPC606242

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605381 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