Natural Product: NPC18877

Natural Product IDNPC18877
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2',4-Dihydroxy-4',6'-Dimethoxydihydrochalcone
IUPAC Name 1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(4-hydroxyphenyl)propan-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL481649
PubChem CID 10266895
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 VFHSXDLCCBWTTJ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H18O5/c1-21-13-9-15(20)17(16(10-13)22-2)14(19)8-5-11-3-6-12(18)7-4-11/h3-4,6-7,9-10,18,20H,5,8H2,1-2H3
SMILES COc1cc(O)c(c(c1)OC)C(=O)CCc1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.12 Volume:   310.971
?
Van der Waals volume.
Dense:   0.972 LogP:   2.728
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.888
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.486
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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:   2.051 Fsp3:   0.235
MCE-18:   13.0
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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:   0.288 Fluc inhibitor:   0.249
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.231
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.342
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.436 Promiscuous compounds:   0.147

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.783 MDCK Permeability:   -4.784
Pgp-inhibitor:   0.967 Pgp-substrate:   0.016
PAMPA:   0.025
?
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):   0.003
20% Bioavailability (F20%):   0.011 30% Bioavailability (F30%):   0.253
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.244
Plasma Protein Binding (PPB):   96.07% Volume Distribution (VD):   0.254
Fu: 3.515%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.711
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.918 CYP1A2-substrate:   0.968
CYP2C19-inhibitor:   0.941 CYP2C19-substrate:   0.909
CYP2C9-inhibitor:   0.943 CYP2C9-substrate:   0.936
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.007
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.997
HLM stability:   0.976
?
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):  8.174 Half-life (T1/2):  0.878

ADMET: Toxicity

hERG Blockers:  0.188 hERG Blockers (10um):  0.628
Human Hepatotoxicity (H-HT):  0.501 Drug-induced Liver Injury (DILI):  0.088
AMES Toxicity:  0.354 Rat Oral Acute Toxicity:  0.289
Maximum Recommended Daily Dose:  0.446 Skin Sensitization:  0.546
Carcinogencity:  0.475 Eye Corrosion:  0.116
Eye Irritation:  0.958 Respiratory Toxicity:  0.73
Drug-induced Neurotoxicity:  0.621 Ototoxicity:  0.258
Hematotoxicity:  0.265 Drug-induced Nephrotoxicity:  0.348
Genotoxicity:  0.526 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.223 Hek293 Cytotoxicity:  0.531
BCF:   1.354
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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:   4.025
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.048
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.492
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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
NPO2754 Iryanthera lancifolia Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[10579855]
NPO2754 Iryanthera lancifolia Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[18242997]
NPO2754 Iryanthera lancifolia Species Myristicaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 4.7 ug ml-1 PMID[10579855]

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 NPC18877 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
0.8182 Intermediate Similarity NPC144051
0.8 Intermediate Similarity NPC28753
0.7333 Intermediate Similarity NPC82225
0.7021 Intermediate Similarity NPC286336
0.64 Remote Similarity NPC20560
0.6349 Remote Similarity NPC6985
0.6349 Remote Similarity NPC106625
0.6154 Remote Similarity NPC282957
0.597 Remote Similarity NPC127406
0.5965 Remote Similarity NPC13575
0.5849 Remote Similarity NPC329203
0.5849 Remote Similarity NPC222342
0.5833 Remote Similarity NPC204960
0.5745 Remote Similarity NPC242895
0.5714 Remote Similarity NPC294593
0.5686 Remote Similarity NPC189106
0.56 Remote Similarity NPC229147
0.56 Remote Similarity NPC604715
0.5577 Remote Similarity NPC112192
0.5536 Remote Similarity NPC472918
0.5536 Remote Similarity NPC284550
0.549 Remote Similarity NPC485643
0.5472 Remote Similarity NPC263670
0.5455 Remote Similarity NPC305518
0.5417 Remote Similarity NPC133909
0.5357 Remote Similarity NPC310135
0.5303 Remote Similarity NPC261271
0.5303 Remote Similarity NPC475348
0.5294 Remote Similarity NPC128348
0.5263 Remote Similarity NPC186097
0.5263 Remote Similarity NPC27139
0.5217 Remote Similarity NPC300537
0.5192 Remote Similarity NPC309717
0.5185 Remote Similarity NPC66384
0.5167 Remote Similarity NPC251681
0.5091 Remote Similarity NPC484336
0.5091 Remote Similarity NPC484337
0.5085 Remote Similarity NPC18585
0.5085 Remote Similarity NPC234152

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC18877 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