Natural Product: NPC231763

Natural Product IDNPC231763
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KIZPADOTOCPASX-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5481234
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0003530] Pyranoisoflavonoids

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 KIZPADOTOCPASX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H16O6/c1-20(2)6-5-12-15(26-20)4-3-11(18(12)23)13-9-25-16-8-10(21)7-14(22)17(16)19(13)24/h3-9,21-23H,1-2H3
SMILES CC1(C)C=Cc2c(ccc(c3coc4cc(cc(c4c3=O)O)O)c2O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   352.09 Volume:   349.264
?
Van der Waals volume.
Dense:   1.008 LogP:   3.274
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.783
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.15
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.616 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.03 Fsp3:   0.15
MCE-18:   52.174
?
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:   0.589 Fluc inhibitor:   0.908
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.738
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.657
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.453 Promiscuous compounds:   0.353

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.123 MDCK Permeability:   -4.802
Pgp-inhibitor:   0.115 Pgp-substrate:   0.068
PAMPA:   0.64
?
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):   0.007
20% Bioavailability (F20%):   0.604 30% Bioavailability (F30%):   0.941
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.076 MRP1:   0.723
Plasma Protein Binding (PPB):   97.599% Volume Distribution (VD):   0.095
Fu: 2.271%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.964
OATP1B3 inhibitor:   0.872 BCRP inhibitor:   0.957
BSEP inhibitor:   0.917

ADMET: Metabolism

CYP1A2-inhibitor:   0.785 CYP1A2-substrate:   0.914
CYP2C19-inhibitor:   0.047 CYP2C19-substrate:   0.282
CYP2C9-inhibitor:   0.978 CYP2C9-substrate:   0.95
CYP2D6-inhibitor:   0.761 CYP2D6-substrate:   0.976
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.348
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
HLM stability:   0.98
?
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):  1.895 Half-life (T1/2):  1.486

ADMET: Toxicity

hERG Blockers:  0.115 hERG Blockers (10um):  0.524
Human Hepatotoxicity (H-HT):  0.467 Drug-induced Liver Injury (DILI):  0.817
AMES Toxicity:  0.681 Rat Oral Acute Toxicity:  0.697
Maximum Recommended Daily Dose:  0.871 Skin Sensitization:  0.493
Carcinogencity:  0.72 Eye Corrosion:  0.003
Eye Irritation:  0.971 Respiratory Toxicity:  0.942
Drug-induced Neurotoxicity:  0.106 Ototoxicity:  0.235
Hematotoxicity:  0.076 Drug-induced Nephrotoxicity:  0.175
Genotoxicity:  0.959 RPMI-8226 Immunitoxicity:  0.109
A549 Cytotoxicity:  0.36 Hek293 Cytotoxicity:  0.692
BCF:   1.408
?
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:   4.334
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.43
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.982
?
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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s40502-015-0143-x]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1093/pcp/pcg054]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443709050069]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443711030101]
NPO29080 Ulex airensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[11858751]
NPO32756 ulex europaeus ssp. europaeus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[11858751]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Leaves n.a. n.a. PMID[12713396]
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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota roots n.a. n.a. PMID[20022509]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21123068]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21866899]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22074222]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. root n.a. PMID[22074222]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23325115]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Roots n.a. n.a. PMID[23541646]
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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28140583]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28522265]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[29641206]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[32196343]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[39683057]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[7381508]
NPO29080 Ulex airensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7786 Lentinus tigrinus Species Lentinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10026 Mitracarpus scaber Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1698 Glycyrrhiza inflata 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]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29080 Ulex airensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7786 Lentinus tigrinus Species Lentinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10026 Mitracarpus scaber Species Rubiaceae 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 = 69.0 % PMID[28522265]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 1.47 n.a. PMID[28835349]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens GI = 14.0 % PMID[28522265]
NPT660 Cell line SW480 Homo sapiens GI = 13.0 % PMID[28522265]
NPT65 Cell line HepG2 Homo sapiens GI = 13.0 % PMID[28522265]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 10.0 % PMID[28522265]
NPT2 Others Unspecified n.a. Inhibition = 4.0 % PMID[28522265]
NPT2 Others Unspecified n.a. Inhibition = 14.0 % PMID[28522265]

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 NPC231763 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
0.75 Intermediate Similarity NPC266572
0.7391 Intermediate Similarity NPC107838
0.7027 Intermediate Similarity NPC238064
0.7 Intermediate Similarity NPC474052
0.6901 Remote Similarity NPC303197
0.6216 Remote Similarity NPC74178
0.6 Remote Similarity NPC84124
0.5949 Remote Similarity NPC303174
0.5942 Remote Similarity NPC279668
0.5811 Remote Similarity NPC233918
0.5802 Remote Similarity NPC113475
0.5753 Remote Similarity NPC97716
0.5735 Remote Similarity NPC294409
0.5735 Remote Similarity NPC490701
0.5714 Remote Similarity NPC104406
0.5584 Remote Similarity NPC134796
0.5556 Remote Similarity NPC605736
0.5541 Remote Similarity NPC232947
0.5538 Remote Similarity NPC39426
0.5513 Remote Similarity NPC609101
0.55 Remote Similarity NPC233502
0.5422 Remote Similarity NPC302762
0.5417 Remote Similarity NPC476055
0.5417 Remote Similarity NPC264550
0.5402 Remote Similarity NPC121647
0.5385 Remote Similarity NPC15435
0.5373 Remote Similarity NPC87545
0.5362 Remote Similarity NPC78341
0.5352 Remote Similarity NPC309154
0.5352 Remote Similarity NPC200316
0.5303 Remote Similarity NPC608554
0.5278 Remote Similarity NPC278323
0.5278 Remote Similarity NPC194653
0.525 Remote Similarity NPC184755
0.5205 Remote Similarity NPC254702
0.5205 Remote Similarity NPC142876
0.5205 Remote Similarity NPC483637
0.5205 Remote Similarity NPC45291
0.5185 Remote Similarity NPC484043
0.5147 Remote Similarity NPC38065
0.5135 Remote Similarity NPC104728
0.5132 Remote Similarity NPC213659
0.5132 Remote Similarity NPC326109
0.5132 Remote Similarity NPC24673
0.5128 Remote Similarity NPC479305
0.5128 Remote Similarity NPC485109
0.5063 Remote Similarity NPC51759
0.5062 Remote Similarity NPC474960
0.5057 Remote Similarity NPC484047

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC231763 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
0.5538 Remote Similarity NPD1510 Phase 2

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