Natural Product: NPC482076

Natural Product IDNPC482076
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DWYGHGCLIOYRFR-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 53783565
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids

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 DWYGHGCLIOYRFR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H18O7/c1-22-13-7-15(24-3)14(23-2)6-10(13)11-8-25-16-5-9(19)4-12(20)17(16)18(11)21/h4-7,11,19-20H,8H2,1-3H3
SMILES COc1cc(c(cc1C1COc2cc(cc(c2C1=O)O)O)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.11 Volume:   337.291
?
Van der Waals volume.
Dense:   1.026 LogP:   2.299
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.599
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.918
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   94.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.878 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.949 Fsp3:   0.278
MCE-18:   60.304
?
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:   0.099 Fluc inhibitor:   0.176
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.238
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.419
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.323 Promiscuous compounds:   0.424

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.117 MDCK Permeability:   -4.81
Pgp-inhibitor:   0.246 Pgp-substrate:   0.046
PAMPA:   0.018
?
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):   0.015
20% Bioavailability (F20%):   0.029 30% Bioavailability (F30%):   0.038
50% Bioavailability (F50%):   0.722

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.781
Plasma Protein Binding (PPB):   96.676% Volume Distribution (VD):   0.341
Fu: 2.887%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.981
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.956
BSEP inhibitor:   0.871

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.952
CYP2C19-inhibitor:   0.953 CYP2C19-substrate:   0.889
CYP2C9-inhibitor:   0.992 CYP2C9-substrate:   0.361
CYP2D6-inhibitor:   0.732 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.022 CYP3A4-substrate:   0.119
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.984
HLM stability:   0.691
?
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):  7.762 Half-life (T1/2):  1.595

ADMET: Toxicity

hERG Blockers:  0.123 hERG Blockers (10um):  0.608
Human Hepatotoxicity (H-HT):  0.594 Drug-induced Liver Injury (DILI):  0.539
AMES Toxicity:  0.508 Rat Oral Acute Toxicity:  0.522
Maximum Recommended Daily Dose:  0.512 Skin Sensitization:  0.452
Carcinogencity:  0.783 Eye Corrosion:  0.018
Eye Irritation:  0.853 Respiratory Toxicity:  0.836
Drug-induced Neurotoxicity:  0.338 Ototoxicity:  0.357
Hematotoxicity:  0.28 Drug-induced Nephrotoxicity:  0.262
Genotoxicity:  0.73 RPMI-8226 Immunitoxicity:  0.123
A549 Cytotoxicity:  0.459 Hek293 Cytotoxicity:  0.671
BCF:   1.108
?
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:   3.426
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.874
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.912
?
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
NPO40124 Erythrina schliebenii Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28112509]
NPO40124 Erythrina schliebenii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT82 Cell line MDA-MB-231 Homo sapiens EC50 = 275000.0 nM PMID[28112509]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 92500.0 nM PMID[28112509]

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 NPC482076 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
0.8302 Intermediate Similarity NPC469575
0.7222 Intermediate Similarity NPC469584
0.6852 Remote Similarity NPC181960
0.6364 Remote Similarity NPC113770
0.625 Remote Similarity NPC260979
0.619 Remote Similarity NPC29777
0.6111 Remote Similarity NPC316480
0.5781 Remote Similarity NPC200574
0.569 Remote Similarity NPC311144
0.5606 Remote Similarity NPC471115
0.5556 Remote Similarity NPC271288
0.5224 Remote Similarity NPC78247
0.5167 Remote Similarity NPC299011

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482076 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