Natural Product: NPC482691

Natural Product IDNPC482691
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MHUCLSFCRWJSHM-QGZVFWFLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132504085
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003473] 2'-Hydroxy-dihydrochalcones

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 MHUCLSFCRWJSHM-QGZVFWFLSA-N
Standard InCHI InChI=1S/C20H20O5/c1-20(2)8-7-13-9-12(3-6-18(13)25-20)10-17(23)19(24)15-5-4-14(21)11-16(15)22/h3-9,11,17,21-23H,10H2,1-2H3/t17-/m1/s1
SMILES CC1(C)C=Cc2cc(ccc2O1)C[C@H](C(=O)c1ccc(cc1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.13 Volume:   351.666
?
Van der Waals volume.
Dense:   0.967 LogP:   3.145
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.007
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.131
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
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:   0.745 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.266 Fsp3:   0.25
MCE-18:   61.6
?
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:   0.513 Fluc inhibitor:   0.721
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.425
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.409
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.43 Promiscuous compounds:   0.101

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.357 MDCK Permeability:   -4.844
Pgp-inhibitor:   0.135 Pgp-substrate:   0.482
PAMPA:   0.67
?
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):   0.0
20% Bioavailability (F20%):   0.069 30% Bioavailability (F30%):   0.437
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.397
Plasma Protein Binding (PPB):   96.816% Volume Distribution (VD):   0.202
Fu: 2.427%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.947
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.855
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.986
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.221
CYP2C9-inhibitor:   0.037 CYP2C9-substrate:   0.041
CYP2D6-inhibitor:   0.024 CYP2D6-substrate:   0.672
CYP3A4-inhibitor:   0.078 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.999
?
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):  3.72 Half-life (T1/2):  1.835

ADMET: Toxicity

hERG Blockers:  0.268 hERG Blockers (10um):  0.451
Human Hepatotoxicity (H-HT):  0.457 Drug-induced Liver Injury (DILI):  0.055
AMES Toxicity:  0.243 Rat Oral Acute Toxicity:  0.053
Maximum Recommended Daily Dose:  0.963 Skin Sensitization:  0.7
Carcinogencity:  0.084 Eye Corrosion:  0.005
Eye Irritation:  0.974 Respiratory Toxicity:  0.919
Drug-induced Neurotoxicity:  0.237 Ototoxicity:  0.35
Hematotoxicity:  0.041 Drug-induced Nephrotoxicity:  0.8
Genotoxicity:  0.76 RPMI-8226 Immunitoxicity:  0.1
A549 Cytotoxicity:  0.007 Hek293 Cytotoxicity:  0.766
BCF:   1.307
?
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:   4.034
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.177
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.685
?
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
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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Leaves n.a. n.a. PMID[12713396]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota roots n.a. n.a. PMID[20022509]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21866899]
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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28140583]
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]
NPO29384 Glycyrrhiza glabra 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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29384 Glycyrrhiza glabra 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[TM-MC]
NPO29384 Glycyrrhiza glabra 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 = 0.2 % PMID[28140583]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 2.2 n.a. PMID[28140583]
NPT741 Individual protein Tyrosinase Homo sapiens Inhibition = 1.0 % PMID[28140583]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 9.3 % PMID[28140583]
NPT65 Cell line HepG2 Homo sapiens Inhibition = 12.3 % PMID[28140583]
NPT81 Cell line A549 Homo sapiens Inhibition = 6.4 % PMID[28140583]
NPT83 Cell line MCF7 Homo sapiens Inhibition = 19.3 % PMID[28140583]
NPT660 Cell line SW480 Homo sapiens Inhibition = 1.9 % PMID[28140583]
NPT2 Others Unspecified n.a. Inhibition = 0.0 % PMID[28140583]

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 NPC482691 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
0.625 Remote Similarity NPC235239
0.6212 Remote Similarity NPC61258
0.5439 Remote Similarity NPC120488
0.5439 Remote Similarity NPC102829
0.5424 Remote Similarity NPC175552
0.5385 Remote Similarity NPC482692
0.5254 Remote Similarity NPC151113
0.5224 Remote Similarity NPC147688
0.5224 Remote Similarity NPC602715

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482691 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