Natural Product: NPC61879

Natural Product IDNPC61879
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 IEDBNTAKVGBZEP-YVMONPNESA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 52937894
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic 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 IEDBNTAKVGBZEP-YVMONPNESA-N
Standard InCHI InChI=1S/C19H21NO5/c1-24-16-11-14(12-17(25-2)19(16)23)5-8-18(22)20-10-9-13-3-6-15(21)7-4-13/h3-8,11-12,21,23H,9-10H2,1-2H3,(H,20,22)/b8-5-
SMILES COc1cc(/C=CC(=NCCc2ccc(cc2)O)O)cc(c1O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   343.14 Volume:   353.923
?
Van der Waals volume.
Dense:   0.97 LogP:   2.11
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.205
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.292
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   14.0
TPSA:   91.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.53 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.542 Fsp3:   0.211
MCE-18:   13.0
?
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:   0
Colloidal aggregators:   0.919 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.213
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.774
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.018 Promiscuous compounds:   0.367

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.179 MDCK Permeability:   -4.87
Pgp-inhibitor:   0.01 Pgp-substrate:   0.482
PAMPA:   0.158
?
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):   0.029
20% Bioavailability (F20%):   0.626 30% Bioavailability (F30%):   0.399
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.584
Plasma Protein Binding (PPB):   96.261% Volume Distribution (VD):   -0.437
Fu: 3.634%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.976 BCRP inhibitor:   0.145
BSEP inhibitor:   0.948

ADMET: Metabolism

CYP1A2-inhibitor:   0.302 CYP1A2-substrate:   0.208
CYP2C19-inhibitor:   0.781 CYP2C19-substrate:   0.125
CYP2C9-inhibitor:   0.939 CYP2C9-substrate:   0.608
CYP2D6-inhibitor:   0.985 CYP2D6-substrate:   0.055
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.008
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.905
HLM stability:   0.501
?
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):  10.347 Half-life (T1/2):  1.428

ADMET: Toxicity

hERG Blockers:  0.277 hERG Blockers (10um):  0.495
Human Hepatotoxicity (H-HT):  0.841 Drug-induced Liver Injury (DILI):  0.157
AMES Toxicity:  0.453 Rat Oral Acute Toxicity:  0.401
Maximum Recommended Daily Dose:  0.688 Skin Sensitization:  0.978
Carcinogencity:  0.487 Eye Corrosion:  0.0
Eye Irritation:  0.507 Respiratory Toxicity:  0.772
Drug-induced Neurotoxicity:  0.204 Ototoxicity:  0.641
Hematotoxicity:  0.083 Drug-induced Nephrotoxicity:  0.563
Genotoxicity:  0.411 RPMI-8226 Immunitoxicity:  0.028
A549 Cytotoxicity:  0.494 Hek293 Cytotoxicity:  0.772
BCF:   0.709
?
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:   3.456
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.488
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.895
?
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
NPO22727 Avena fatua Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21569 Helichrysum fulvum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16798 Piper sylvaticum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21569 Helichrysum fulvum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22727 Avena fatua Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16798 Piper sylvaticum Species Piperaceae 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
NPT34 Cell line BV-2 Mus musculus IC50 > 50000.0 nM PMID[33822610]

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 NPC61879 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
1.0 High Similarity NPC296898
0.8113 Intermediate Similarity NPC195749
0.8113 Intermediate Similarity NPC35961
0.7455 Intermediate Similarity NPC52029
0.7347 Intermediate Similarity NPC24101
0.7091 Intermediate Similarity NPC214869
0.6923 Remote Similarity NPC122009
0.6923 Remote Similarity NPC96224
0.6842 Remote Similarity NPC178571
0.6842 Remote Similarity NPC155838
0.6604 Remote Similarity NPC480468
0.6316 Remote Similarity NPC251571
0.5902 Remote Similarity NPC222039
0.5902 Remote Similarity NPC100478
0.5714 Remote Similarity NPC283468
0.5676 Remote Similarity NPC90984
0.5556 Remote Similarity NPC153644
0.5556 Remote Similarity NPC299583
0.5556 Remote Similarity NPC204848
0.5556 Remote Similarity NPC160607
0.5556 Remote Similarity NPC41473
0.5556 Remote Similarity NPC312770
0.55 Remote Similarity NPC301713
0.5493 Remote Similarity NPC107602
0.5472 Remote Similarity NPC203076
0.5424 Remote Similarity NPC186898
0.541 Remote Similarity NPC114102
0.54 Remote Similarity NPC178902
0.5325 Remote Similarity NPC50380
0.5325 Remote Similarity NPC179250
0.5246 Remote Similarity NPC485985
0.5077 Remote Similarity NPC14600

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC61879 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