Natural Product: NPC32463

Natural Product IDNPC32463
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7-Dihydroxy-8-(3-Methylbut-2-Enyl)-4-Phenylchromen-2-One
IUPAC Name 5,7-dihydroxy-8-(3-methylbut-2-enyl)-4-phenylchromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL363624
PubChem CID 6483315
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0001614] Neoflavonoids
        • [CHEMONTID:0003650] Prenylated neoflavonoids

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 SRGRDIADLLPPQM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H18O4/c1-12(2)8-9-14-16(21)11-17(22)19-15(10-18(23)24-20(14)19)13-6-4-3-5-7-13/h3-8,10-11,21-22H,9H2,1-2H3
SMILES CC(=CCc1c(cc(c2c(cc(=O)oc12)c1ccccc1)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   322.12 Volume:   340.24
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Van der Waals volume.
Dense:   0.947 LogP:   3.872
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.362
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.481
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   70.67
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.554 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.556 Fsp3:   0.15
MCE-18:   18.0
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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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.936 Fluc inhibitor:   0.061
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.992
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.733
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.287 Promiscuous compounds:   0.127

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.022 MDCK Permeability:   -4.641
Pgp-inhibitor:   0.653 Pgp-substrate:   0.282
PAMPA:   0.116
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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):   0.012
20% Bioavailability (F20%):   0.393 30% Bioavailability (F30%):   0.883
50% Bioavailability (F50%):   0.954

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.084 MRP1:   0.95
Plasma Protein Binding (PPB):   97.364% Volume Distribution (VD):   0.012
Fu: 2.059%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.956
OATP1B3 inhibitor:   0.581 BCRP inhibitor:   0.535
BSEP inhibitor:   0.94

ADMET: Metabolism

CYP1A2-inhibitor:   0.692 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.988 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.992
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.252 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.037 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
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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):  4.404 Half-life (T1/2):  1.003

ADMET: Toxicity

hERG Blockers:  0.046 hERG Blockers (10um):  0.415
Human Hepatotoxicity (H-HT):  0.582 Drug-induced Liver Injury (DILI):  0.903
AMES Toxicity:  0.63 Rat Oral Acute Toxicity:  0.71
Maximum Recommended Daily Dose:  0.74 Skin Sensitization:  0.735
Carcinogencity:  0.556 Eye Corrosion:  0.003
Eye Irritation:  0.838 Respiratory Toxicity:  0.965
Drug-induced Neurotoxicity:  0.171 Ototoxicity:  0.154
Hematotoxicity:  0.173 Drug-induced Nephrotoxicity:  0.371
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.082
A549 Cytotoxicity:  0.241 Hek293 Cytotoxicity:  0.623
BCF:   1.672
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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:   4.661
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.087
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.539
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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
NPO33501 marila pluricostata Species Calophyllaceae Eukaryota leaves n.a. n.a. PMID[15787438]

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
NPT459 Individual protein Human immunodeficiency virus type 1 reverse transcriptase Human immunodeficiency virus 1 IC50 = 11200.0 nM PMID[21051535]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT165 Cell line HeLa Homo sapiens Inhibition = 15.4 % PMID[21051535]
NPT460 Cell line MT2 Homo sapiens Cell death = 34.4 % PMID[16137881]
NPT83 Cell line MCF7 Homo sapiens GI50 = 3.4 ug.mL-1 PMID[17854154]
NPT397 Cell line NCI-H460 Homo sapiens GI50 = 4.4 ug.mL-1 PMID[26836364]
NPT395 Cell line SF-268 Homo sapiens GI50 = 4.8 ug.mL-1 PMID[18183025]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 33.4 % PMID[16137881]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 84.5 % PMID[16137881]

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 NPC32463 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
0.6364 Remote Similarity NPC470296
0.6364 Remote Similarity NPC196459
0.6364 Remote Similarity NPC36181
0.629 Remote Similarity NPC154217
0.6269 Remote Similarity NPC1886
0.5821 Remote Similarity NPC87609
0.5652 Remote Similarity NPC188632
0.5652 Remote Similarity NPC112791
0.5652 Remote Similarity NPC94794
0.5571 Remote Similarity NPC196137
0.5479 Remote Similarity NPC19238
0.5362 Remote Similarity NPC131950
0.5345 Remote Similarity NPC168259
0.5342 Remote Similarity NPC483434
0.5342 Remote Similarity NPC470322
0.5231 Remote Similarity NPC606140
0.5139 Remote Similarity NPC73776

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC32463 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