Natural Product: NPC112192

Natural Product IDNPC112192
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Loureirin A
IUPAC Name 3-(2,4-dimethoxyphenyl)-1-(4-hydroxyphenyl)propan-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL253779
PubChem CID 5319081
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003475] Retro-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 RSAIVLRELNGZEY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H18O4/c1-20-15-9-5-13(17(11-15)21-2)6-10-16(19)12-3-7-14(18)8-4-12/h3-5,7-9,11,18H,6,10H2,1-2H3
SMILES COc1ccc(CCC(=O)c2ccc(cc2)O)c(c1)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.12 Volume:   302.181
?
Van der Waals volume.
Dense:   0.947 LogP:   2.955
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.073
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.594
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   13.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.828 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.787 Fsp3:   0.235
MCE-18:   12.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.369 Fluc inhibitor:   0.858
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.075
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.427
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.693 Promiscuous compounds:   0.234

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.687 MDCK Permeability:   -4.692
Pgp-inhibitor:   0.992 Pgp-substrate:   0.007
PAMPA:   0.005
?
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):   0.013
20% Bioavailability (F20%):   0.012 30% Bioavailability (F30%):   0.183
50% Bioavailability (F50%):   0.897

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.146
Plasma Protein Binding (PPB):   92.419% Volume Distribution (VD):   0.11
Fu: 6.353%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.948
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.982 CYP1A2-substrate:   0.989
CYP2C19-inhibitor:   0.739 CYP2C19-substrate:   0.904
CYP2C9-inhibitor:   0.817 CYP2C9-substrate:   0.444
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.064
CYP2B6-substrate:   0.192 CYP2C8-inhibitor:   0.999
HLM stability:   0.994
?
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):  9.853 Half-life (T1/2):  0.585

ADMET: Toxicity

hERG Blockers:  0.298 hERG Blockers (10um):  0.641
Human Hepatotoxicity (H-HT):  0.338 Drug-induced Liver Injury (DILI):  0.139
AMES Toxicity:  0.331 Rat Oral Acute Toxicity:  0.246
Maximum Recommended Daily Dose:  0.367 Skin Sensitization:  0.261
Carcinogencity:  0.523 Eye Corrosion:  0.119
Eye Irritation:  0.948 Respiratory Toxicity:  0.801
Drug-induced Neurotoxicity:  0.745 Ototoxicity:  0.175
Hematotoxicity:  0.282 Drug-induced Nephrotoxicity:  0.38
Genotoxicity:  0.446 RPMI-8226 Immunitoxicity:  0.044
A549 Cytotoxicity:  0.142 Hek293 Cytotoxicity:  0.587
BCF:   1.176
?
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:   4.003
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.875
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.508
?
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
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. PMID[12016928]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota stems Ningming County, Guangxi autonomous region, China 2006-Jan PMID[17883259]
NPO20812 Soymida febrifuga Species Meliaceae Eukaryota n.a. Myanmar n.a. PMID[19689125]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. PMID[19919095]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. PMID[21661731]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota flower buds and leaves Khon Kaen province, Thailand 2010 PMID[23270663]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Leaves n.a. n.a. PMID[23642481]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Flowers n.a. n.a. PMID[26462418]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20812 Soymida febrifuga Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO495 Daemonorops draco Species Arecaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO495 Daemonorops draco Species Arecaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO495 Daemonorops draco Species Arecaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO495 Daemonorops draco Species Arecaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20812 Soymida febrifuga Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO495 Daemonorops draco Species Arecaceae 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
NPT604 Individual protein Serum albumin Homo sapiens deltaG = -29.23 kJ/mol PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens deltaG = -29.28 kJ/mol PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens deltaH = -31.98 kJ/mol PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens K = 8.56 10'4/M PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens K = 9.51 10'4/M PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens K = 12.91 10'4/M PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens Kq = 6.24 10'12/M/s PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens Kq = 7.98 10'12/M/s PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens Kq = 9.85 10'12/M/s PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens KSV = 6.24 10'4/M PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens KSV = 7.98 10'4/M PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens KSV = 9.85 10'4/M PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens deltaG = -29.19 kJ/mol PMID[25734332]
NPT604 Individual protein Serum albumin Homo sapiens Activity = 28.0 % PMID[25734332]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT453 Cell line HT-1080 Homo sapiens IC50 > 100000.0 nM PMID[19689125]
NPT461 Cell line PANC-1 Homo sapiens PC50 = 83.2 uM PMID[19689125]
NPT81 Cell line A549 Homo sapiens IC50 = 89500.0 nM PMID[19689125]
NPT165 Cell line HeLa Homo sapiens IC50 > 100000.0 nM PMID[19689125]
NPT451 Organism Helicobacter pylori Helicobacter pylori MIC = 223800.0 nM PMID[17883259]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 32200.0 nM PMID[19689125]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 55500.0 nM PMID[19689125]

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 NPC112192 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
0.7333 Intermediate Similarity NPC309717
0.6458 Remote Similarity NPC189106
0.6383 Remote Similarity NPC128348
0.5882 Remote Similarity NPC100099
0.5882 Remote Similarity NPC66384
0.5833 Remote Similarity NPC471523
0.5714 Remote Similarity NPC164236
0.5577 Remote Similarity NPC18877
0.5556 Remote Similarity NPC471524
0.5472 Remote Similarity NPC296874
0.5323 Remote Similarity NPC471473
0.5208 Remote Similarity NPC159525
0.5192 Remote Similarity NPC286336
0.5185 Remote Similarity NPC282000
0.5098 Remote Similarity NPC82225
0.5094 Remote Similarity NPC207732
0.5088 Remote Similarity NPC27139

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC112192 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