Natural Product: NPC475680

Natural Product IDNPC475680
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isolonchocarpin
IUPAC Name (E)-1-(7-hydroxy-2,2-dimethylchromen-6-yl)-3-phenylprop-2-en-1-one
Synonyms Isolonchocarpin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL511336
PubChem CID 44588270
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003472] 2'-Hydroxychalcones

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 KVXNRZVPNCKCNO-CMDGGOBGSA-N
Standard InCHI InChI=1S/C20H18O3/c1-20(2)11-10-15-12-16(18(22)13-19(15)23-20)17(21)9-8-14-6-4-3-5-7-14/h3-13,22H,1-2H3/b9-8+
SMILES O=C(c1cc2C=CC(Oc2cc1O)(C)C)/C=C/c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   306.13 Volume:   331.449
?
Van der Waals volume.
Dense:   0.924 LogP:   4.637
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.888
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.003
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   46.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.672 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.58 Fsp3:   0.15
MCE-18:   37.565
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.999 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.857
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.96
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.778 Promiscuous compounds:   0.261

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.987 MDCK Permeability:   -4.704
Pgp-inhibitor:   0.999 Pgp-substrate:   0.001
PAMPA:   0.049
?
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):   0.002
20% Bioavailability (F20%):   0.879 30% Bioavailability (F30%):   0.995
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.019 MRP1:   0.023
Plasma Protein Binding (PPB):   98.666% Volume Distribution (VD):   -0.057
Fu: 0.839%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.869
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.849
CYP2C9-inhibitor:   0.116 CYP2C9-substrate:   0.281
CYP2D6-inhibitor:   0.312 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.132
?
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):  7.683 Half-life (T1/2):  0.75

ADMET: Toxicity

hERG Blockers:  0.325 hERG Blockers (10um):  0.583
Human Hepatotoxicity (H-HT):  0.623 Drug-induced Liver Injury (DILI):  0.495
AMES Toxicity:  0.479 Rat Oral Acute Toxicity:  0.247
Maximum Recommended Daily Dose:  0.626 Skin Sensitization:  0.776
Carcinogencity:  0.301 Eye Corrosion:  0.013
Eye Irritation:  0.958 Respiratory Toxicity:  0.73
Drug-induced Neurotoxicity:  0.729 Ototoxicity:  0.235
Hematotoxicity:  0.159 Drug-induced Nephrotoxicity:  0.414
Genotoxicity:  0.341 RPMI-8226 Immunitoxicity:  0.082
A549 Cytotoxicity:  0.203 Hek293 Cytotoxicity:  0.499
BCF:   1.706
?
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:   4.77
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.278
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.849
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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
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota stem bark Indonesia 1999-SEP PMID[14510596]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. stem n.a. PMID[14510596]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota dry stem n.a. n.a. PMID[25466192]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota Roots n.a. n.a. PMID[29482940]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]

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
NPT34 Cell line BV-2 Mus musculus IC50 > 100000.0 nM PMID[25466192]
NPT19 Organism Escherichia coli Escherichia coli MIC = 2000.0 ug.mL-1 PMID[23398362]
NPT19 Organism Escherichia coli Escherichia coli MBC > 2000.0 ug ml-1 PMID[26034885]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC = 2000.0 ug.mL-1 PMID[22365754]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MBC > 2000.0 ug ml-1 PMID[19627125]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 2000.0 ug.mL-1 PMID[19650637]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MBC > 2000.0 ug ml-1 PMID[24513045]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 1000.0 ug.mL-1 PMID[10924160]
NPT314 Organism Bacillus cereus Bacillus cereus MBC > 2000.0 ug ml-1 PMID[22705001]

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 NPC475680 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
0.8269 Intermediate Similarity NPC147688
0.6939 Remote Similarity NPC151113
0.6607 Remote Similarity NPC305355
0.6167 Remote Similarity NPC235239
0.5833 Remote Similarity NPC11561
0.5833 Remote Similarity NPC602715
0.5574 Remote Similarity NPC209397
0.5455 Remote Similarity NPC64359
0.541 Remote Similarity NPC156590
0.5224 Remote Similarity NPC10027
0.5161 Remote Similarity NPC269694
0.5147 Remote Similarity NPC6118
0.5091 Remote Similarity NPC212631
0.5091 Remote Similarity NPC608685
0.5085 Remote Similarity NPC150399
0.5082 Remote Similarity NPC240593

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC475680 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