Natural Product: NPC59319

Natural Product IDNPC59319
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ISKWCIVFBIHFTG-XBXARRHUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10472405
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003509] 3-prenylated chalcones

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 ISKWCIVFBIHFTG-XBXARRHUSA-N
Standard InCHI InChI=1S/C20H20O5/c1-12(2)3-6-14-17(22)10-7-15(20(14)25)16(21)8-4-13-5-9-18(23)19(24)11-13/h3-5,7-11,22-25H,6H2,1-2H3/b8-4+
SMILES CC(=CCc1c(ccc(C(=O)/C=C/c2ccc(c(c2)O)O)c1O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.13 Volume:   357.586
?
Van der Waals volume.
Dense:   0.951 LogP:   3.721
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.315
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.342
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   15.0
TPSA:   97.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.286 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.608 Fsp3:   0.15
MCE-18:   15.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.986 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.64
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.676
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.664 Promiscuous compounds:   0.276

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.052 MDCK Permeability:   -4.787
Pgp-inhibitor:   0.053 Pgp-substrate:   0.001
PAMPA:   0.232
?
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):   0.083
20% Bioavailability (F20%):   0.99 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.242
Plasma Protein Binding (PPB):   95.076% Volume Distribution (VD):   -0.109
Fu: 4.415%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.358
BSEP inhibitor:   0.302

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.994
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.75
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.594
CYP2D6-inhibitor:   0.577 CYP2D6-substrate:   0.636
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.988
?
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):  8.586 Half-life (T1/2):  1.353

ADMET: Toxicity

hERG Blockers:  0.072 hERG Blockers (10um):  0.673
Human Hepatotoxicity (H-HT):  0.493 Drug-induced Liver Injury (DILI):  0.374
AMES Toxicity:  0.563 Rat Oral Acute Toxicity:  0.391
Maximum Recommended Daily Dose:  0.636 Skin Sensitization:  0.998
Carcinogencity:  0.125 Eye Corrosion:  0.01
Eye Irritation:  0.976 Respiratory Toxicity:  0.932
Drug-induced Neurotoxicity:  0.122 Ototoxicity:  0.531
Hematotoxicity:  0.04 Drug-induced Nephrotoxicity:  0.214
Genotoxicity:  0.902 RPMI-8226 Immunitoxicity:  0.041
A549 Cytotoxicity:  0.861 Hek293 Cytotoxicity:  0.643
BCF:   1.495
?
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:   4.613
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.952
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.54
?
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
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21123068]
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]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1698 Glycyrrhiza inflata 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]
NPO1698 Glycyrrhiza inflata 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]
NPO1698 Glycyrrhiza inflata 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 = 16.0 % PMID[28522265]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 1.56 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 = 12.0 % PMID[28522265]
NPT660 Cell line SW480 Homo sapiens GI = 11.0 % PMID[28522265]
NPT65 Cell line HepG2 Homo sapiens GI = 1.0 % PMID[28522265]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 11.0 % 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 NPC59319 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
0.8333 Intermediate Similarity NPC72158
0.8148 Intermediate Similarity NPC264112
0.7959 Intermediate Similarity NPC62952
0.7843 Intermediate Similarity NPC100067
0.7037 Intermediate Similarity NPC479645
0.7037 Intermediate Similarity NPC479648
0.6981 Remote Similarity NPC162612
0.6842 Remote Similarity NPC266689
0.6667 Remote Similarity NPC194764
0.625 Remote Similarity NPC213485
0.623 Remote Similarity NPC21305
0.6154 Remote Similarity NPC237994
0.6129 Remote Similarity NPC19622
0.6129 Remote Similarity NPC112789
0.6129 Remote Similarity NPC475042
0.6129 Remote Similarity NPC470210
0.5965 Remote Similarity NPC481727
0.5965 Remote Similarity NPC481726
0.5938 Remote Similarity NPC484872
0.5893 Remote Similarity NPC98254
0.5882 Remote Similarity NPC26697
0.5862 Remote Similarity NPC65005
0.5806 Remote Similarity NPC484873
0.5789 Remote Similarity NPC169250
0.5714 Remote Similarity NPC190043
0.5645 Remote Similarity NPC474998
0.5614 Remote Similarity NPC103356
0.5577 Remote Similarity NPC34070
0.5441 Remote Similarity NPC275903
0.5439 Remote Similarity NPC30501
0.541 Remote Similarity NPC249606
0.5333 Remote Similarity NPC168105
0.5205 Remote Similarity NPC479647
0.5205 Remote Similarity NPC479646
0.5205 Remote Similarity NPC155253
0.52 Remote Similarity NPC482707
0.5179 Remote Similarity NPC284556
0.5135 Remote Similarity NPC85393
0.5094 Remote Similarity NPC122793
0.5082 Remote Similarity NPC269694
0.5082 Remote Similarity NPC482693
0.5079 Remote Similarity NPC473017
0.5077 Remote Similarity NPC40524
0.5075 Remote Similarity NPC6118

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59319 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