Natural Product: NPC482707

Natural Product IDNPC482707
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DOWSJIIZLUFMFM-DAFODLJHSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10038861
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003474] Retrochalcones

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 DOWSJIIZLUFMFM-DAFODLJHSA-N
Standard InCHI InChI=1S/C15H12O5/c16-11(10-3-6-13(18)15(20)8-10)4-1-9-2-5-12(17)14(19)7-9/h1-8,17-20H/b4-1+
SMILES C(=CC(=O)c1ccc(c(c1)O)O)/c1ccc(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.07 Volume:   273.743
?
Van der Waals volume.
Dense:   0.994 LogP:   1.907
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.924
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.209
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
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:   0.391 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.186 Fsp3:   0.0
MCE-18:   13.0
?
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:   0.974 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.17
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.459
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.942 Promiscuous compounds:   0.766

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.983 MDCK Permeability:   -4.79
Pgp-inhibitor:   0.002 Pgp-substrate:   0.002
PAMPA:   0.211
?
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):   0.045
20% Bioavailability (F20%):   0.996 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.121
Plasma Protein Binding (PPB):   90.03% Volume Distribution (VD):   -0.293
Fu: 10.815%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.428
BSEP inhibitor:   0.082

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.091
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.027
?
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):  19.588 Half-life (T1/2):  1.801

ADMET: Toxicity

hERG Blockers:  0.17 hERG Blockers (10um):  0.749
Human Hepatotoxicity (H-HT):  0.429 Drug-induced Liver Injury (DILI):  0.556
AMES Toxicity:  0.452 Rat Oral Acute Toxicity:  0.158
Maximum Recommended Daily Dose:  0.676 Skin Sensitization:  0.998
Carcinogencity:  0.215 Eye Corrosion:  0.322
Eye Irritation:  0.997 Respiratory Toxicity:  0.421
Drug-induced Neurotoxicity:  0.042 Ototoxicity:  0.65
Hematotoxicity:  0.032 Drug-induced Nephrotoxicity:  0.026
Genotoxicity:  0.855 RPMI-8226 Immunitoxicity:  0.007
A549 Cytotoxicity:  0.883 Hek293 Cytotoxicity:  0.341
BCF:   1.144
?
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:   3.975
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.962
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.743
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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
NPT144 Individual protein Telomerase reverse transcriptase Homo sapiens IC50 = 1700.0 nM PMID[15588081]
NPT1310 Individual protein Xanthine dehydrogenase Bos taurus IC50 = 3000.0 nM PMID[26762836]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 1.0 % PMID[28522265]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 1.85 n.a. PMID[28835349]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition < 20.0 % PMID[17267225]

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 = 5.0 % PMID[28522265]
NPT660 Cell line SW480 Homo sapiens GI = 10.0 % PMID[28522265]
NPT65 Cell line HepG2 Homo sapiens GI = 8.0 % PMID[28522265]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 1.0 % PMID[28522265]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 40.0 % PMID[26762836]
NPT35 Others n.a. n.a. Activity = 77.0 % PMID[26762836]
NPT2 Others Unspecified n.a. Inhibition = 13.0 % PMID[28522265]
NPT2 Others Unspecified n.a. Inhibition = 16.0 % PMID[28522265]
NPT2 Others Unspecified n.a. IC50 = 15600.0 nM PMID[28242551]

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 NPC482707 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
0.6667 Remote Similarity NPC17525
0.6341 Remote Similarity NPC26697
0.6341 Remote Similarity NPC34070
0.5833 Remote Similarity NPC19149
0.5778 Remote Similarity NPC312256
0.5778 Remote Similarity NPC284556
0.5676 Remote Similarity NPC79672
0.5652 Remote Similarity NPC301178
0.5588 Remote Similarity NPC150919
0.5532 Remote Similarity NPC102003
0.5532 Remote Similarity NPC471417
0.5349 Remote Similarity NPC122793
0.525 Remote Similarity NPC226250
0.5238 Remote Similarity NPC95381
0.52 Remote Similarity NPC194764
0.52 Remote Similarity NPC59319
0.5135 Remote Similarity NPC131587
0.5106 Remote Similarity NPC66905

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482707 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