Natural Product: NPC265183

Natural Product IDNPC265183
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XNNKDPTVDXENLP-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11957911
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
            • [CHEMONTID:0002687] 4'-O-methylisoflavones

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 XNNKDPTVDXENLP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O4/c1-13(2)4-9-16-19(22)11-10-17-20(23)18(12-25-21(16)17)14-5-7-15(24-3)8-6-14/h4-8,10-12,22H,9H2,1-3H3
SMILES CC(=CCc1c(ccc2c(=O)c(coc12)c1ccc(cc1)OC)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   336.14 Volume:   357.536
?
Van der Waals volume.
Dense:   0.94 LogP:   4.241
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.738
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.726
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.703 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.414 Fsp3:   0.19
MCE-18:   18.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.955 Fluc inhibitor:   0.953
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.984
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.763
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.341 Promiscuous compounds:   0.093

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.763 MDCK Permeability:   -4.598
Pgp-inhibitor:   0.835 Pgp-substrate:   0.031
PAMPA:   0.161
?
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):   0.266
20% Bioavailability (F20%):   0.902 30% Bioavailability (F30%):   0.937
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.651
Plasma Protein Binding (PPB):   92.858% Volume Distribution (VD):   0.303
Fu: 6.479%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.956
BSEP inhibitor:   0.97

ADMET: Metabolism

CYP1A2-inhibitor:   0.304 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.977 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.994 CYP2C9-substrate:   0.555
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.479
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.258 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):  6.114 Half-life (T1/2):  0.632

ADMET: Toxicity

hERG Blockers:  0.147 hERG Blockers (10um):  0.591
Human Hepatotoxicity (H-HT):  0.537 Drug-induced Liver Injury (DILI):  0.841
AMES Toxicity:  0.722 Rat Oral Acute Toxicity:  0.744
Maximum Recommended Daily Dose:  0.624 Skin Sensitization:  0.529
Carcinogencity:  0.639 Eye Corrosion:  0.001
Eye Irritation:  0.678 Respiratory Toxicity:  0.958
Drug-induced Neurotoxicity:  0.612 Ototoxicity:  0.371
Hematotoxicity:  0.282 Drug-induced Nephrotoxicity:  0.582
Genotoxicity:  0.9 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.264 Hek293 Cytotoxicity:  0.541
BCF:   1.881
?
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:   4.842
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.396
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.865
?
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

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 NPC265183 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
0.7077 Intermediate Similarity NPC172250
0.6875 Remote Similarity NPC478987
0.6232 Remote Similarity NPC193564
0.6 Remote Similarity NPC40942
0.5972 Remote Similarity NPC604255
0.5846 Remote Similarity NPC69430
0.5846 Remote Similarity NPC209560
0.5846 Remote Similarity NPC490700
0.5846 Remote Similarity NPC610981
0.5753 Remote Similarity NPC149875
0.5676 Remote Similarity NPC610891
0.5652 Remote Similarity NPC144118
0.5455 Remote Similarity NPC333691
0.5352 Remote Similarity NPC38545
0.5352 Remote Similarity NPC606446
0.5352 Remote Similarity NPC607923
0.5224 Remote Similarity NPC10467
0.5224 Remote Similarity NPC603503
0.5195 Remote Similarity NPC256406
0.5147 Remote Similarity NPC121522
0.5139 Remote Similarity NPC204985
0.5135 Remote Similarity NPC80962
0.5122 Remote Similarity NPC349624
0.5077 Remote Similarity NPC182428
0.5075 Remote Similarity NPC474264
0.5068 Remote Similarity NPC273538
0.5067 Remote Similarity NPC130589

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC265183 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
0.5068 Remote Similarity NPD4378 Phase 3

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