Natural Product: NPC269285

Natural Product IDNPC269285
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RFPGFYAPDRVXAE-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 52935997
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0003502] 3'-prenylated flavones

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 RFPGFYAPDRVXAE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O6/c1-11(2)4-5-12-8-13(6-7-15(12)23)20-21(26-3)19(25)18-16(24)9-14(22)10-17(18)27-20/h4,6-10,22-24H,5H2,1-3H3
SMILES CC(=CCc1cc(ccc1O)c1c(c(=O)c2c(cc(cc2o1)O)O)OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.13 Volume:   375.116
?
Van der Waals volume.
Dense:   0.981 LogP:   4.014
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.331
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.617
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.6 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.725 Fsp3:   0.19
MCE-18:   20.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.675 Fluc inhibitor:   0.551
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.949
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.789
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.266 Promiscuous compounds:   0.093

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.026 MDCK Permeability:   -4.799
Pgp-inhibitor:   0.182 Pgp-substrate:   0.134
PAMPA:   0.642
?
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):   0.069
20% Bioavailability (F20%):   0.95 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.817
Plasma Protein Binding (PPB):   95.41% Volume Distribution (VD):   0.255
Fu: 4.207%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.036
OATP1B3 inhibitor:   0.916 BCRP inhibitor:   0.999
BSEP inhibitor:   0.928

ADMET: Metabolism

CYP1A2-inhibitor:   0.404 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.98 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.253 CYP2C9-substrate:   0.053
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.934
CYP3A4-inhibitor:   0.148 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  5.587 Half-life (T1/2):  1.126

ADMET: Toxicity

hERG Blockers:  0.056 hERG Blockers (10um):  0.512
Human Hepatotoxicity (H-HT):  0.486 Drug-induced Liver Injury (DILI):  0.768
AMES Toxicity:  0.65 Rat Oral Acute Toxicity:  0.659
Maximum Recommended Daily Dose:  0.74 Skin Sensitization:  0.872
Carcinogencity:  0.68 Eye Corrosion:  0.038
Eye Irritation:  0.971 Respiratory Toxicity:  0.873
Drug-induced Neurotoxicity:  0.115 Ototoxicity:  0.185
Hematotoxicity:  0.094 Drug-induced Nephrotoxicity:  0.161
Genotoxicity:  0.983 RPMI-8226 Immunitoxicity:  0.066
A549 Cytotoxicity:  0.417 Hek293 Cytotoxicity:  0.733
BCF:   1.714
?
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:   4.582
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.719
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.248
?
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
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11164-015-2099-x]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443711030101]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[16441081]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16675659]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[22074222]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22074222]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. rhizome n.a. PMID[23867078]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[23867078]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24479468]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota roots n.a. n.a. PMID[24957203]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25445757]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25744461]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[26841168]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[32196343]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7154 Glycyrrhiza uralensis Species Fabaceae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 85.0 % PMID[26841168]
NPT1480 Individual protein Fibroblast growth factor receptor 1 Homo sapiens Inhibition = 34.1 % PMID[36549116]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus Inhibition > 50.0 % PMID[26841168]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 12100.0 nM PMID[26841168]
NPT65 Cell line HepG2 Homo sapiens IC50 = 50510.0 nM PMID[36549116]
NPT20904 Cell line Hep 3B2 Homo sapiens IC50 = 990.0 nM PMID[36549116]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 87.1 % PMID[36549116]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 2.29 % PMID[36549116]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 1.97 % PMID[36549116]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 8.68 % PMID[36549116]

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 NPC269285 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
0.8361 Intermediate Similarity NPC158874
0.7846 Intermediate Similarity NPC97255
0.7612 Intermediate Similarity NPC470458
0.7324 Intermediate Similarity NPC470461
0.7015 Intermediate Similarity NPC301217
0.7015 Intermediate Similarity NPC200694
0.6986 Remote Similarity NPC470460
0.6774 Remote Similarity NPC103342
0.6714 Remote Similarity NPC56786
0.6667 Remote Similarity NPC286342
0.6571 Remote Similarity NPC259632
0.6471 Remote Similarity NPC246478
0.6286 Remote Similarity NPC306488
0.6269 Remote Similarity NPC279989
0.625 Remote Similarity NPC184536
0.6154 Remote Similarity NPC59951
0.6 Remote Similarity NPC123886
0.597 Remote Similarity NPC82325
0.5946 Remote Similarity NPC470459
0.5909 Remote Similarity NPC610359
0.5882 Remote Similarity NPC162351
0.5882 Remote Similarity NPC603596
0.5833 Remote Similarity NPC213659
0.5833 Remote Similarity NPC326109
0.5789 Remote Similarity NPC158761
0.575 Remote Similarity NPC80534
0.5714 Remote Similarity NPC470457
0.5694 Remote Similarity NPC293053
0.5694 Remote Similarity NPC205046
0.55 Remote Similarity NPC470462
0.5479 Remote Similarity NPC216978
0.5479 Remote Similarity NPC261227
0.5405 Remote Similarity NPC59210
0.5405 Remote Similarity NPC270708
0.5309 Remote Similarity NPC133392
0.5205 Remote Similarity NPC172986
0.5195 Remote Similarity NPC224714
0.5072 Remote Similarity NPC266960
0.5065 Remote Similarity NPC76833
0.5065 Remote Similarity NPC233918

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC269285 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