Natural Product: NPC263676

Natural Product IDNPC263676
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Pongamol
IUPAC Name (Z)-3-hydroxy-1-(4-methoxy-1-benzofuran-5-yl)-3-phenylprop-2-en-1-one
Synonyms Pongamol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL458131
PubChem CID 5320675
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003542] Furanochalcones

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 IHWPQGIYXJKCOV-PTNGSMBKSA-N
Standard InCHI InChI=1S/C18H14O4/c1-21-18-13(7-8-17-14(18)9-10-22-17)16(20)11-15(19)12-5-3-2-4-6-12/h2-11,19H,1H3/b15-11-
SMILES COc1c(ccc2c1cco2)C(=O)/C=C(/c1ccccc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   294.09 Volume:   305.648
?
Van der Waals volume.
Dense:   0.962 LogP:   2.983
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.063
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.033
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.444 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.359 Fsp3:   0.056
MCE-18:   16.0
?
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:   0.448 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.759
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.513
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.67 Promiscuous compounds:   0.089

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.672 MDCK Permeability:   -4.712
Pgp-inhibitor:   0.113 Pgp-substrate:   0.011
PAMPA:   0.785
?
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):   0.009
20% Bioavailability (F20%):   0.017 30% Bioavailability (F30%):   0.107
50% Bioavailability (F50%):   0.561

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.077 MRP1:   0.744
Plasma Protein Binding (PPB):   98.687% Volume Distribution (VD):   -0.641
Fu: 0.906%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.98
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.086
BSEP inhibitor:   0.894

ADMET: Metabolism

CYP1A2-inhibitor:   0.155 CYP1A2-substrate:   0.859
CYP2C19-inhibitor:   0.075 CYP2C19-substrate:   0.39
CYP2C9-inhibitor:   0.788 CYP2C9-substrate:   0.027
CYP2D6-inhibitor:   0.955 CYP2D6-substrate:   0.069
CYP3A4-inhibitor:   0.365 CYP3A4-substrate:   0.283
CYP2B6-substrate:   0.021 CYP2C8-inhibitor:   0.729
HLM stability:   0.831
?
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):  1.889 Half-life (T1/2):  1.172

ADMET: Toxicity

hERG Blockers:  0.078 hERG Blockers (10um):  0.039
Human Hepatotoxicity (H-HT):  0.831 Drug-induced Liver Injury (DILI):  0.992
AMES Toxicity:  0.302 Rat Oral Acute Toxicity:  0.313
Maximum Recommended Daily Dose:  0.236 Skin Sensitization:  0.106
Carcinogencity:  0.508 Eye Corrosion:  0.001
Eye Irritation:  0.994 Respiratory Toxicity:  0.815
Drug-induced Neurotoxicity:  0.12 Ototoxicity:  0.331
Hematotoxicity:  0.251 Drug-induced Nephrotoxicity:  0.656
Genotoxicity:  0.304 RPMI-8226 Immunitoxicity:  0.015
A549 Cytotoxicity:  0.015 Hek293 Cytotoxicity:  0.066
BCF:   1.164
?
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:   4.062
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.013
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.704
?
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
NPO21911 Tephrosia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[10814365]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. stem n.a. PMID[14510596]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota stem bark Indonesia 1999-SEP PMID[14510596]
NPO31471 Poncirus trifoliata Species Rutaceae Eukaryota n.a. fruit n.a. PMID[17666859]
NPO3037 Derris indica Species Fabaceae Eukaryota root n.a. n.a. PMID[19515570]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. fruit n.a. PMID[23872723]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota dry stem n.a. n.a. PMID[25466192]
NPO19856 Millettia pulchra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25630222]
NPO21911 Tephrosia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[26476665]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota Roots n.a. n.a. PMID[29482940]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[32996318]
NPO21911 Tephrosia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9322358]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31471 Poncirus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19856 Millettia pulchra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19432 Millettia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3037 Derris indica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21911 Tephrosia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31471 Poncirus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21911 Tephrosia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21911 Tephrosia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19432 Millettia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21911 Tephrosia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31471 Poncirus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19432 Millettia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21911 Tephrosia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19856 Millettia pulchra 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
NPT2794 Individual protein Quinolone resistance protein norA Staphylococcus aureus MIC = 4.0 ug.mL-1 DOI[10.1039/C4MD00196F]
NPT2794 Individual protein Quinolone resistance protein norA Staphylococcus aureus FC = 2.0 n.a. DOI[10.1039/C4MD00196F]
NPT2795 Individual protein Fluoroquinolone resistance protein Staphylococcus aureus MIC = 256.0 ug.mL-1 DOI[10.1039/C4MD00196F]
NPT2795 Individual protein Fluoroquinolone resistance protein Staphylococcus aureus FC = 0.0 n.a. DOI[10.1039/C4MD00196F]
NPT1603 Individual protein Cytochrome P450 1A1 Homo sapiens Activity = 73.0 % PMID[30448188]
NPT1603 Individual protein Cytochrome P450 1A1 Homo sapiens EC50 = 10200.0 nM PMID[30448188]
NPT1604 Individual protein Cytochrome P450 1B1 Homo sapiens IC50 = 4500.0 nM PMID[30448188]
NPT1603 Individual protein Cytochrome P450 1A1 Homo sapiens IC50 = 4400.0 nM PMID[30448188]
NPT1604 Individual protein Cytochrome P450 1B1 Homo sapiens IC50 = 3900.0 nM PMID[30448188]
NPT1603 Individual protein Cytochrome P450 1A1 Homo sapiens IC50 = 2400.0 nM PMID[30448188]
NPT365 Individual protein NAD(P)H dehydrogenase [quinone] 1 Mus musculus Ratio = 1.69 n.a. PMID[25630222]
NPT440 Individual protein Quinone oxidoreductase Mus musculus CD = 6.1 uM PMID[9322358]
NPT668 Individual protein P-glycoprotein 1 Homo sapiens IC50 = 88000.0 nM DOI[10.1039/C4MD00196F]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT15 Cell line Jurkat Homo sapiens Activity = 17.0 % DOI[10.1007/s00044-011-9563-y]
NPT165 Cell line HeLa Homo sapiens Activity = 23.0 % DOI[10.1007/s00044-011-9563-y]
NPT744 Cell line IMR-32 Homo sapiens Activity = 38.0 % DOI[10.1007/s00044-011-9563-y]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 18700.0 nM PMID[9322358]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 78.0 % PMID[25630222]
NPT1 Others Radical scavenging activity n.a. SC50 = 11.2 % PMID[19515570]
NPT2 Others Unspecified n.a. Ratio = 3.1 n.a. PMID[9322358]
NPT2 Others Unspecified n.a. Activity = 103.5 uM PMID[19515570]
NPT2 Others Unspecified n.a. IC50 = 58.2 % PMID[19515570]
NPT2 Others Unspecified n.a. MIC = 32.0 ug.mL-1 DOI[10.1039/C4MD00196F]
NPT2 Others Unspecified n.a. FC = 0.0 n.a. DOI[10.1039/C4MD00196F]
NPT2 Others Unspecified n.a. MIC = 64.0 ug.mL-1 DOI[10.1039/C4MD00196F]

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 NPC263676 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
0.7049 Intermediate Similarity NPC157522
0.6667 Remote Similarity NPC198427
0.6316 Remote Similarity NPC160049
0.5806 Remote Similarity NPC472406
0.5088 Remote Similarity NPC473193

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC263676 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