Natural Product: NPC109223

Natural Product IDNPC109223
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CGKWSLSAYABZTL-SFHVURJKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14218028
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003643] 3'-prenylated flavans
            • [CHEMONTID:0003506] 3'-prenylated flavanones

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 CGKWSLSAYABZTL-SFHVURJKSA-N
Standard InCHI InChI=1S/C20H20O5/c1-11(2)3-4-12-7-13(5-6-15(12)22)18-10-17(24)20-16(23)8-14(21)9-19(20)25-18/h3,5-9,18,21-23H,4,10H2,1-2H3/t18-/m0/s1
SMILES CC(=CCc1cc(ccc1O)[C@@H]1CC(=O)c2c(cc(cc2O1)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.13 Volume:   351.666
?
Van der Waals volume.
Dense:   0.967 LogP:   3.994
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.472
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.442
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.735 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.212 Fsp3:   0.25
MCE-18:   60.04
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.801 Fluc inhibitor:   0.939
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.317
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.422
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.381 Promiscuous compounds:   0.098

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.956 MDCK Permeability:   -4.778
Pgp-inhibitor:   0.398 Pgp-substrate:   0.06
PAMPA:   0.294
?
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):   0.011
20% Bioavailability (F20%):   0.839 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.831
Plasma Protein Binding (PPB):   94.916% Volume Distribution (VD):   0.398
Fu: 4.694%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.891
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.999
BSEP inhibitor:   0.519

ADMET: Metabolism

CYP1A2-inhibitor:   0.091 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.499 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.013 CYP2C9-substrate:   0.05
CYP2D6-inhibitor:   0.346 CYP2D6-substrate:   0.971
CYP3A4-inhibitor:   0.0 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):  8.043 Half-life (T1/2):  1.192

ADMET: Toxicity

hERG Blockers:  0.094 hERG Blockers (10um):  0.519
Human Hepatotoxicity (H-HT):  0.766 Drug-induced Liver Injury (DILI):  0.803
AMES Toxicity:  0.799 Rat Oral Acute Toxicity:  0.853
Maximum Recommended Daily Dose:  0.809 Skin Sensitization:  0.949
Carcinogencity:  0.474 Eye Corrosion:  0.002
Eye Irritation:  0.954 Respiratory Toxicity:  0.969
Drug-induced Neurotoxicity:  0.732 Ototoxicity:  0.472
Hematotoxicity:  0.157 Drug-induced Nephrotoxicity:  0.809
Genotoxicity:  0.997 RPMI-8226 Immunitoxicity:  0.151
A549 Cytotoxicity:  0.874 Hek293 Cytotoxicity:  0.802
BCF:   1.807
?
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:   4.636
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.901
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.3
?
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]
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. root n.a. PMID[23867078]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. rhizome 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]
NPO7786 Lentinus tigrinus Species Lentinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29384 Glycyrrhiza glabra 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]
NPO10026 Mitracarpus scaber Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7154 Glycyrrhiza uralensis Species Fabaceae 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]
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[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[TM-MC]
NPO29384 Glycyrrhiza glabra 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[TM-MC]
NPO29384 Glycyrrhiza glabra 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]
NPO7154 Glycyrrhiza uralensis Species Fabaceae 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 > 60.0 % PMID[32196343]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Activity = 80.0 % PMID[32196343]
NPT2 Others Unspecified n.a. Inhibition > 40.0 % PMID[32196343]

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 NPC109223 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
1.0 High Similarity NPC10937
0.8364 Intermediate Similarity NPC258630
0.7797 Intermediate Similarity NPC106976
0.75 Intermediate Similarity NPC125855
0.7458 Intermediate Similarity NPC221432
0.7458 Intermediate Similarity NPC257097
0.7419 Intermediate Similarity NPC470890
0.7419 Intermediate Similarity NPC200761
0.7333 Intermediate Similarity NPC17170
0.7049 Intermediate Similarity NPC66515
0.6909 Remote Similarity NPC32441
0.6909 Remote Similarity NPC79943
0.6842 Remote Similarity NPC321011
0.6842 Remote Similarity NPC294852
0.6842 Remote Similarity NPC188679
0.6825 Remote Similarity NPC85121
0.6567 Remote Similarity NPC474021
0.6522 Remote Similarity NPC227579
0.6522 Remote Similarity NPC214166
0.6522 Remote Similarity NPC185276
0.6452 Remote Similarity NPC39329
0.6452 Remote Similarity NPC51032
0.6429 Remote Similarity NPC111786
0.6324 Remote Similarity NPC96408
0.6324 Remote Similarity NPC610511
0.6316 Remote Similarity NPC243083
0.6316 Remote Similarity NPC13768
0.6316 Remote Similarity NPC287246
0.6308 Remote Similarity NPC608140
0.629 Remote Similarity NPC143896
0.625 Remote Similarity NPC197252
0.6197 Remote Similarity NPC74924
0.619 Remote Similarity NPC150408
0.614 Remote Similarity NPC182421
0.6129 Remote Similarity NPC236637
0.6129 Remote Similarity NPC197351
0.6119 Remote Similarity NPC312973
0.6111 Remote Similarity NPC474023
0.6102 Remote Similarity NPC274784
0.6102 Remote Similarity NPC20709
0.6056 Remote Similarity NPC58805
0.6034 Remote Similarity NPC295261
0.6034 Remote Similarity NPC296490
0.6027 Remote Similarity NPC43319
0.5946 Remote Similarity NPC122365
0.5938 Remote Similarity NPC107572
0.5938 Remote Similarity NPC32739
0.5909 Remote Similarity NPC223500
0.589 Remote Similarity NPC474024
0.589 Remote Similarity NPC186686
0.5846 Remote Similarity NPC477841
0.5833 Remote Similarity NPC338131
0.5833 Remote Similarity NPC107586
0.5821 Remote Similarity NPC174953
0.5806 Remote Similarity NPC302950
0.5797 Remote Similarity NPC88964
0.5775 Remote Similarity NPC279650
0.5763 Remote Similarity NPC12296
0.5758 Remote Similarity NPC220998
0.5753 Remote Similarity NPC67396
0.5735 Remote Similarity NPC161506
0.5735 Remote Similarity NPC134783
0.5714 Remote Similarity NPC118256
0.5714 Remote Similarity NPC39752
0.5692 Remote Similarity NPC1089
0.5672 Remote Similarity NPC166689
0.5652 Remote Similarity NPC291508
0.5652 Remote Similarity NPC475790
0.5606 Remote Similarity NPC69674
0.5571 Remote Similarity NPC35038
0.5571 Remote Similarity NPC611447
0.5538 Remote Similarity NPC169591
0.5538 Remote Similarity NPC298223
0.5538 Remote Similarity NPC604412
0.5522 Remote Similarity NPC68104
0.5479 Remote Similarity NPC474038
0.5455 Remote Similarity NPC324436
0.5455 Remote Similarity NPC78
0.5455 Remote Similarity NPC236766
0.5417 Remote Similarity NPC473272
0.5417 Remote Similarity NPC228504
0.5395 Remote Similarity NPC24640
0.5373 Remote Similarity NPC171651
0.5373 Remote Similarity NPC75049
0.5362 Remote Similarity NPC108456
0.5352 Remote Similarity NPC473990
0.5303 Remote Similarity NPC164980
0.5303 Remote Similarity NPC76372
0.5303 Remote Similarity NPC37496
0.5303 Remote Similarity NPC482704
0.5238 Remote Similarity NPC469764
0.5217 Remote Similarity NPC76338
0.5217 Remote Similarity NPC250242
0.52 Remote Similarity NPC475784
0.5147 Remote Similarity NPC265040
0.5147 Remote Similarity NPC148757
0.5143 Remote Similarity NPC278476
0.5139 Remote Similarity NPC69531
0.5135 Remote Similarity NPC213896
0.5132 Remote Similarity NPC209040
0.5132 Remote Similarity NPC298692
0.5128 Remote Similarity NPC602605
0.5079 Remote Similarity NPC300668
0.5079 Remote Similarity NPC329203
0.5079 Remote Similarity NPC324386
0.5079 Remote Similarity NPC222342
0.5068 Remote Similarity NPC166934
0.5068 Remote Similarity NPC272502
0.5067 Remote Similarity NPC224851
0.5067 Remote Similarity NPC488556

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC109223 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
0.6909 Remote Similarity NPD1552 Clinical (unspecified phase)
0.6316 Remote Similarity NPD1550 Phase 2
0.5806 Remote Similarity NPD1934 Phase 0

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