Natural Product: NPC310655

Natural Product IDNPC310655
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KBEFFXBSHFUQLT-KRWDZBQOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 13845972
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-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 KBEFFXBSHFUQLT-KRWDZBQOSA-N
Standard InCHI InChI=1S/C20H20O6/c1-10(2)3-5-12-14(22)8-18-19(20(12)25)16(24)9-17(26-18)11-4-6-13(21)15(23)7-11/h3-4,6-8,17,21-23,25H,5,9H2,1-2H3/t17-/m0/s1
SMILES CC(=CCc1c(cc2c(C(=O)C[C@@H](c3ccc(c(c3)O)O)O2)c1O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.13 Volume:   360.456
?
Van der Waals volume.
Dense:   0.988 LogP:   3.536
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.206
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.699
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   107.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.493 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.32 Fsp3:   0.25
MCE-18:   63.2
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.792 Fluc inhibitor:   0.787
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.683
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.48
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.409 Promiscuous compounds:   0.157

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.074 MDCK Permeability:   -4.776
Pgp-inhibitor:   0.879 Pgp-substrate:   0.002
PAMPA:   0.723
?
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):   0.119
20% Bioavailability (F20%):   0.171 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.881
Plasma Protein Binding (PPB):   95.004% Volume Distribution (VD):   0.054
Fu: 4.915%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.993
BSEP inhibitor:   0.875

ADMET: Metabolism

CYP1A2-inhibitor:   0.122 CYP1A2-substrate:   0.995
CYP2C19-inhibitor:   0.72 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   0.214 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.376 CYP2D6-substrate:   0.99
CYP3A4-inhibitor:   0.043 CYP3A4-substrate:   0.999
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):  10.916 Half-life (T1/2):  1.538

ADMET: Toxicity

hERG Blockers:  0.038 hERG Blockers (10um):  0.614
Human Hepatotoxicity (H-HT):  0.65 Drug-induced Liver Injury (DILI):  0.448
AMES Toxicity:  0.81 Rat Oral Acute Toxicity:  0.73
Maximum Recommended Daily Dose:  0.63 Skin Sensitization:  0.989
Carcinogencity:  0.414 Eye Corrosion:  0.001
Eye Irritation:  0.977 Respiratory Toxicity:  0.747
Drug-induced Neurotoxicity:  0.24 Ototoxicity:  0.646
Hematotoxicity:  0.082 Drug-induced Nephrotoxicity:  0.571
Genotoxicity:  0.989 RPMI-8226 Immunitoxicity:  0.074
A549 Cytotoxicity:  0.886 Hek293 Cytotoxicity:  0.627
BCF:   1.646
?
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:   4.352
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.982
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.246
?
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. 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]
NPO7154 Glycyrrhiza uralensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[32196343]
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]
NPO7786 Lentinus tigrinus Species Lentinaceae 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]
NPO7786 Lentinus tigrinus Species Lentinaceae 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

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 NPC310655 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 NPC213896
0.8103 Intermediate Similarity NPC125855
0.7895 Intermediate Similarity NPC1089
0.7812 Intermediate Similarity NPC261063
0.7692 Intermediate Similarity NPC321779
0.7581 Intermediate Similarity NPC35038
0.7213 Intermediate Similarity NPC223500
0.7077 Intermediate Similarity NPC228504
0.7049 Intermediate Similarity NPC610133
0.7015 Intermediate Similarity NPC185276
0.6912 Remote Similarity NPC298692
0.6667 Remote Similarity NPC278778
0.6667 Remote Similarity NPC166689
0.6618 Remote Similarity NPC488556
0.6567 Remote Similarity NPC290133
0.6522 Remote Similarity NPC472627
0.6479 Remote Similarity NPC45849
0.6479 Remote Similarity NPC195796
0.6471 Remote Similarity NPC472629
0.6471 Remote Similarity NPC64915
0.6377 Remote Similarity NPC164272
0.6377 Remote Similarity NPC470327
0.6364 Remote Similarity NPC223787
0.6338 Remote Similarity NPC472628
0.6271 Remote Similarity NPC321011
0.6271 Remote Similarity NPC294852
0.6271 Remote Similarity NPC188679
0.625 Remote Similarity NPC210459
0.625 Remote Similarity NPC488557
0.6197 Remote Similarity NPC226025
0.6164 Remote Similarity NPC27337
0.6143 Remote Similarity NPC470328
0.6143 Remote Similarity NPC267375
0.6143 Remote Similarity NPC209614
0.6081 Remote Similarity NPC488555
0.6081 Remote Similarity NPC484418
0.6027 Remote Similarity NPC472626
0.6 Remote Similarity NPC109223
0.6 Remote Similarity NPC474055
0.6 Remote Similarity NPC10937
0.5946 Remote Similarity NPC472598
0.5921 Remote Similarity NPC472634
0.5909 Remote Similarity NPC106976
0.5909 Remote Similarity NPC480158
0.589 Remote Similarity NPC488554
0.5846 Remote Similarity NPC69674
0.5846 Remote Similarity NPC265040
0.5833 Remote Similarity NPC22192
0.5821 Remote Similarity NPC608140
0.5781 Remote Similarity NPC258630
0.5758 Remote Similarity NPC220998
0.5753 Remote Similarity NPC488558
0.5714 Remote Similarity NPC293319
0.5692 Remote Similarity NPC39329
0.5692 Remote Similarity NPC51032
0.5676 Remote Similarity NPC472630
0.5652 Remote Similarity NPC470890
0.5641 Remote Similarity NPC321399
0.56 Remote Similarity NPC472631
0.5574 Remote Similarity NPC482119
0.5574 Remote Similarity NPC482120
0.5574 Remote Similarity NPC324386
0.5455 Remote Similarity NPC13575
0.541 Remote Similarity NPC1612
0.541 Remote Similarity NPC183959
0.5373 Remote Similarity NPC221432
0.5373 Remote Similarity NPC95936
0.5373 Remote Similarity NPC187282
0.5373 Remote Similarity NPC257097
0.5303 Remote Similarity NPC143896
0.5294 Remote Similarity NPC17170
0.5238 Remote Similarity NPC192083
0.5224 Remote Similarity NPC107572
0.5224 Remote Similarity NPC32739
0.5217 Remote Similarity NPC285555
0.5217 Remote Similarity NPC76338
0.5217 Remote Similarity NPC250242
0.5205 Remote Similarity NPC484416
0.5205 Remote Similarity NPC474021
0.52 Remote Similarity NPC58805
0.5161 Remote Similarity NPC312391
0.5075 Remote Similarity NPC169591
0.5075 Remote Similarity NPC298223
0.5075 Remote Similarity NPC249606
0.5075 Remote Similarity NPC604412
0.5072 Remote Similarity NPC66515
0.5067 Remote Similarity NPC262039

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC310655 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
0.5238 Remote Similarity NPD2393 Clinical (unspecified phase)

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