Natural Product: NPC257462

Natural Product IDNPC257462
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NTKOJTKKDRUJDE-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10915521
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0003520] Pyranoflavonoids

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 NTKOJTKKDRUJDE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H18O6/c1-21(2)7-6-12-16(27-21)10-18-19(20(12)24)14(23)9-15(26-18)11-4-5-13(22)17(8-11)25-3/h4-10,22,24H,1-3H3
SMILES CC1(C)C=Cc2c(cc3c(c(=O)cc(c4ccc(c(c4)OC)O)o3)c2O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   366.11 Volume:   366.56
?
Van der Waals volume.
Dense:   0.999 LogP:   3.698
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.036
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.201
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   23.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.711 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.843 Fsp3:   0.19
MCE-18:   52.0
?
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:   0.528 Fluc inhibitor:   0.856
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.931
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.777
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.337 Promiscuous compounds:   0.399

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.973 MDCK Permeability:   -4.713
Pgp-inhibitor:   0.948 Pgp-substrate:   0.018
PAMPA:   0.218
?
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):   0.006
20% Bioavailability (F20%):   0.78 30% Bioavailability (F30%):   0.948
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.985
Plasma Protein Binding (PPB):   98.075% Volume Distribution (VD):   -0.068
Fu: 1.714%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.998
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.1 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.14 CYP2C19-substrate:   0.492
CYP2C9-inhibitor:   0.978 CYP2C9-substrate:   0.732
CYP2D6-inhibitor:   0.978 CYP2D6-substrate:   0.974
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.932
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.897
?
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):  4.84 Half-life (T1/2):  1.187

ADMET: Toxicity

hERG Blockers:  0.081 hERG Blockers (10um):  0.481
Human Hepatotoxicity (H-HT):  0.403 Drug-induced Liver Injury (DILI):  0.703
AMES Toxicity:  0.654 Rat Oral Acute Toxicity:  0.583
Maximum Recommended Daily Dose:  0.775 Skin Sensitization:  0.743
Carcinogencity:  0.764 Eye Corrosion:  0.099
Eye Irritation:  0.981 Respiratory Toxicity:  0.883
Drug-induced Neurotoxicity:  0.082 Ototoxicity:  0.124
Hematotoxicity:  0.145 Drug-induced Nephrotoxicity:  0.132
Genotoxicity:  0.835 RPMI-8226 Immunitoxicity:  0.112
A549 Cytotoxicity:  0.272 Hek293 Cytotoxicity:  0.633
BCF:   1.486
?
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:   4.06
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.394
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.764
?
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
NPO23982 Ventilago leiocarpa Species Rhamnaceae Eukaryota n.a. n.a. n.a. PMID[11374975]
NPO13726 Agrobacterium tumefaciens Species Rhizobiaceae Bacteria n.a. n.a. n.a. PMID[22466953]
NPO13726 Agrobacterium tumefaciens Species Rhizobiaceae Bacteria n.a. n.a. n.a. PMID[24450804]
NPO13726 Agrobacterium tumefaciens Species Rhizobiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO21356.1 Helichrysum arenarium subsp. aucheri Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23982 Ventilago leiocarpa Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23982 Ventilago leiocarpa Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23982 Ventilago leiocarpa Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13726 Agrobacterium tumefaciens Species Rhizobiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO21356.1 Helichrysum arenarium subsp. aucheri Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23982 Ventilago leiocarpa Species Rhamnaceae 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

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 NPC257462 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
0.7846 Intermediate Similarity NPC265932
0.7 Intermediate Similarity NPC59739
0.6324 Remote Similarity NPC137062
0.6087 Remote Similarity NPC47781
0.6 Remote Similarity NPC602497
0.5949 Remote Similarity NPC478511
0.5811 Remote Similarity NPC65491
0.5797 Remote Similarity NPC83508
0.5714 Remote Similarity NPC473076
0.5694 Remote Similarity NPC255133
0.5658 Remote Similarity NPC70272
0.5652 Remote Similarity NPC78913
0.5634 Remote Similarity NPC183950
0.5634 Remote Similarity NPC606105
0.5571 Remote Similarity NPC20830
0.5467 Remote Similarity NPC479166
0.5443 Remote Similarity NPC229632
0.5429 Remote Similarity NPC312924
0.5417 Remote Similarity NPC227325
0.5375 Remote Similarity NPC184755
0.5375 Remote Similarity NPC472450
0.5375 Remote Similarity NPC275780
0.5352 Remote Similarity NPC280339
0.5325 Remote Similarity NPC479165
0.5286 Remote Similarity NPC18260
0.5278 Remote Similarity NPC4455
0.5278 Remote Similarity NPC128863
0.5278 Remote Similarity NPC115323
0.5263 Remote Similarity NPC97716
0.525 Remote Similarity NPC214236
0.5195 Remote Similarity NPC293852
0.5176 Remote Similarity NPC321623
0.5139 Remote Similarity NPC167815
0.5128 Remote Similarity NPC170492
0.5125 Remote Similarity NPC184547
0.5119 Remote Similarity NPC478512
0.5119 Remote Similarity NPC78803
0.5065 Remote Similarity NPC101957
0.5065 Remote Similarity NPC166054

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC257462 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