Natural Product: NPC128348

Natural Product IDNPC128348
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4,4'-Dihydroxy-2,6-Dimethoxydihydrochalcone
IUPAC Name 3-(4-hydroxy-2,6-dimethoxyphenyl)-1-(4-hydroxyphenyl)propan-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL400283
PubChem CID 10424988
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 WRSUVSOOJHAIRI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H18O5/c1-21-16-9-13(19)10-17(22-2)14(16)7-8-15(20)11-3-5-12(18)6-4-11/h3-6,9-10,18-19H,7-8H2,1-2H3
SMILES COc1cc(O)cc(c1CCC(=O)c1ccc(cc1)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.12 Volume:   310.971
?
Van der Waals volume.
Dense:   0.972 LogP:   2.604
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.633
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.745
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   13.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.802 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.098 Fsp3:   0.235
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.289 Fluc inhibitor:   0.222
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.15
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.44
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.488 Promiscuous compounds:   0.167

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.717 MDCK Permeability:   -4.776
Pgp-inhibitor:   0.093 Pgp-substrate:   0.035
PAMPA:   0.07
?
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):   0.001
20% Bioavailability (F20%):   0.017 30% Bioavailability (F30%):   0.031
50% Bioavailability (F50%):   0.782

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.626
Plasma Protein Binding (PPB):   92.987% Volume Distribution (VD):   0.157
Fu: 6.705%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.967
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.439
BSEP inhibitor:   0.957

ADMET: Metabolism

CYP1A2-inhibitor:   0.017 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.142 CYP2C19-substrate:   0.989
CYP2C9-inhibitor:   0.645 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.891 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.038 CYP3A4-substrate:   0.751
CYP2B6-substrate:   0.185 CYP2C8-inhibitor:   1.0
HLM stability:   0.977
?
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):  9.705 Half-life (T1/2):  1.049

ADMET: Toxicity

hERG Blockers:  0.226 hERG Blockers (10um):  0.607
Human Hepatotoxicity (H-HT):  0.363 Drug-induced Liver Injury (DILI):  0.081
AMES Toxicity:  0.287 Rat Oral Acute Toxicity:  0.253
Maximum Recommended Daily Dose:  0.466 Skin Sensitization:  0.316
Carcinogencity:  0.486 Eye Corrosion:  0.112
Eye Irritation:  0.964 Respiratory Toxicity:  0.738
Drug-induced Neurotoxicity:  0.608 Ototoxicity:  0.123
Hematotoxicity:  0.2 Drug-induced Nephrotoxicity:  0.184
Genotoxicity:  0.714 RPMI-8226 Immunitoxicity:  0.041
A549 Cytotoxicity:  0.108 Hek293 Cytotoxicity:  0.663
BCF:   1.039
?
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:   3.736
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.558
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.076
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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
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]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. PMID[21661731]
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]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12714 Dracaena cochinchinensis Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20812 Soymida febrifuga Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12714 Dracaena cochinchinensis Species Asparagaceae 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
NPT453 Cell line HT-1080 Homo sapiens IC50 = 67200.0 nM PMID[21616566]
NPT461 Cell line PANC-1 Homo sapiens PC50 = 69.7 uM PMID[19689125]
NPT81 Cell line A549 Homo sapiens IC50 = 42900.0 nM PMID[226705]
NPT165 Cell line HeLa Homo sapiens IC50 = 49000.0 nM PMID[18811205]
NPT451 Organism Helicobacter pylori Helicobacter pylori MIC = 211900.0 nM DrugMatrix in vivo data: Hematology
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 40200.0 nM PMID[19689125]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 84400.0 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 NPC128348 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
0.8049 Intermediate Similarity NPC164236
0.7442 Intermediate Similarity NPC309717
0.6957 Remote Similarity NPC66384
0.6522 Remote Similarity NPC189106
0.6383 Remote Similarity NPC112192
0.58 Remote Similarity NPC296874
0.5556 Remote Similarity NPC159525
0.5417 Remote Similarity NPC82225
0.54 Remote Similarity NPC207732
0.5333 Remote Similarity NPC471523
0.5333 Remote Similarity NPC471473
0.5294 Remote Similarity NPC18877
0.52 Remote Similarity NPC286336
0.5094 Remote Similarity NPC282957
0.5079 Remote Similarity NPC471524

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC128348 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