Natural Product: NPC480468

Natural Product IDNPC480468
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KZUJJPCTENPKOE-XBXARRHUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11630793
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives
          • [CHEMONTID:0000059] Coumaric acids and derivatives

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 KZUJJPCTENPKOE-XBXARRHUSA-N
Standard InCHI InChI=1S/C17H17NO4/c19-14-5-1-12(2-6-14)4-8-17(22)18-10-9-13-3-7-15(20)16(21)11-13/h1-8,11,19-21H,9-10H2,(H,18,22)/b8-4+
SMILES c1cc(ccc1/C=C/C(=NCCc1ccc(c(c1)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   299.12 Volume:   310.541
?
Van der Waals volume.
Dense:   0.963 LogP:   2.129
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.245
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.22
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   93.28
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.388 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.587 Fsp3:   0.118
MCE-18:   12.0
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.979 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.244
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.656
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.096 Promiscuous compounds:   0.408

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.963 MDCK Permeability:   -4.807
Pgp-inhibitor:   0.001 Pgp-substrate:   0.069
PAMPA:   0.562
?
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):   0.043
20% Bioavailability (F20%):   0.999 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.011
Plasma Protein Binding (PPB):   93.81% Volume Distribution (VD):   -0.273
Fu: 6.919%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.97 BCRP inhibitor:   0.018
BSEP inhibitor:   0.794

ADMET: Metabolism

CYP1A2-inhibitor:   0.074 CYP1A2-substrate:   0.091
CYP2C19-inhibitor:   0.007 CYP2C19-substrate:   0.256
CYP2C9-inhibitor:   0.755 CYP2C9-substrate:   0.018
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.875
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.555
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.698
?
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):  15.219 Half-life (T1/2):  1.459

ADMET: Toxicity

hERG Blockers:  0.238 hERG Blockers (10um):  0.563
Human Hepatotoxicity (H-HT):  0.865 Drug-induced Liver Injury (DILI):  0.571
AMES Toxicity:  0.671 Rat Oral Acute Toxicity:  0.417
Maximum Recommended Daily Dose:  0.69 Skin Sensitization:  0.999
Carcinogencity:  0.405 Eye Corrosion:  0.002
Eye Irritation:  0.874 Respiratory Toxicity:  0.769
Drug-induced Neurotoxicity:  0.068 Ototoxicity:  0.722
Hematotoxicity:  0.055 Drug-induced Nephrotoxicity:  0.182
Genotoxicity:  0.8 RPMI-8226 Immunitoxicity:  0.006
A549 Cytotoxicity:  0.526 Hek293 Cytotoxicity:  0.498
BCF:   1.12
?
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:   3.79
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.684
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.38
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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
NPO17083 Atraphaxis frutescens Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[28006914]
NPO17083 Atraphaxis frutescens Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17083 Atraphaxis frutescens Species Polygonaceae 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
NPT204 Individual protein Acetylcholinesterase Homo sapiens EC50 = 16870.0 nM PMID[37856864]
NPT439 Individual protein Butyrylcholinesterase Homo sapiens EC50 = 41290.0 nM PMID[37856864]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT3915 Organism Helicoverpa armigera Helicoverpa armigera Activity = 65.1 % PMID[37856864]
NPT2 Others Unspecified n.a. IC50 = 1630.0 nM PMID[26974386]
NPT2 Others Unspecified n.a. Ki = 1740.0 nM PMID[26974386]
NPT35 Others n.a. n.a. IC50 = 72100.0 nM PMID[28006914]
NPT2 Others Unspecified n.a. IC50 = 92800.0 nM PMID[28006914]
NPT2 Others Unspecified n.a. IC50 = 4300000.0 nM PMID[28006914]

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 NPC480468 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
0.881 High Similarity NPC24101
0.8636 High Similarity NPC122009
0.7826 Intermediate Similarity NPC96224
0.7083 Intermediate Similarity NPC283468
0.6981 Remote Similarity NPC178571
0.6667 Remote Similarity NPC52029
0.6667 Remote Similarity NPC195749
0.6667 Remote Similarity NPC35961
0.6604 Remote Similarity NPC61879
0.6604 Remote Similarity NPC296898
0.6415 Remote Similarity NPC251571
0.617 Remote Similarity NPC203076
0.6 Remote Similarity NPC214869
0.5882 Remote Similarity NPC268572
0.5778 Remote Similarity NPC178902
0.5714 Remote Similarity NPC223548
0.5517 Remote Similarity NPC155838
0.5397 Remote Similarity NPC99666
0.5273 Remote Similarity NPC142297

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC480468 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