Natural Product: NPC109675

Natural Product IDNPC109675
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7-Dimethoxy-8-[(Z)-3-Methylbut-1,3-Dienyl)]Coumarin
IUPAC Name 5,7-dimethoxy-8-[(1Z)-3-methylbuta-1,3-dienyl]chromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3426666
PubChem CID 10612228
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives

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 XUEBXQXWALAJLA-WAYWQWQTSA-N
Standard InCHI InChI=1S/C16H16O4/c1-10(2)5-6-11-13(18-3)9-14(19-4)12-7-8-15(17)20-16(11)12/h5-9H,1H2,2-4H3/b6-5-
SMILES COc1cc(OC)c2c(c1/C=CC(=C)C)oc(=O)cc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.1 Volume:   284.885
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Van der Waals volume.
Dense:   0.955 LogP:   3.006
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.037
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.035
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   14.0
TPSA:   48.67
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.632 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.712 Fsp3:   0.188
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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.38 Fluc inhibitor:   0.54
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.913
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.725
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.525 Promiscuous compounds:   0.177

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.53 MDCK Permeability:   -4.639
Pgp-inhibitor:   0.33 Pgp-substrate:   0.004
PAMPA:   0.019
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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):   0.152
20% Bioavailability (F20%):   0.77 30% Bioavailability (F30%):   0.84
50% Bioavailability (F50%):   0.968

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.021 MRP1:   0.554
Plasma Protein Binding (PPB):   97.851% Volume Distribution (VD):   0.122
Fu: 1.748%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.448
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.974 CYP1A2-substrate:   0.444
CYP2C19-inhibitor:   0.972 CYP2C19-substrate:   0.076
CYP2C9-inhibitor:   0.982 CYP2C9-substrate:   0.012
CYP2D6-inhibitor:   0.865 CYP2D6-substrate:   0.968
CYP3A4-inhibitor:   0.193 CYP3A4-substrate:   0.774
CYP2B6-substrate:   0.997 CYP2C8-inhibitor:   0.646
HLM stability:   0.958
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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):  10.213 Half-life (T1/2):  0.735

ADMET: Toxicity

hERG Blockers:  0.088 hERG Blockers (10um):  0.379
Human Hepatotoxicity (H-HT):  0.594 Drug-induced Liver Injury (DILI):  0.589
AMES Toxicity:  0.521 Rat Oral Acute Toxicity:  0.46
Maximum Recommended Daily Dose:  0.733 Skin Sensitization:  0.726
Carcinogencity:  0.619 Eye Corrosion:  0.79
Eye Irritation:  0.979 Respiratory Toxicity:  0.663
Drug-induced Neurotoxicity:  0.392 Ototoxicity:  0.172
Hematotoxicity:  0.32 Drug-induced Nephrotoxicity:  0.212
Genotoxicity:  0.824 RPMI-8226 Immunitoxicity:  0.107
A549 Cytotoxicity:  0.108 Hek293 Cytotoxicity:  0.296
BCF:   1.288
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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:   3.951
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.33
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.71
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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
NPO33003 murraya alata Species Rutaceae Eukaryota leaves n.a. n.a. PMID[25621853]
NPO33003 murraya alata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 14500.0 nM PMID[24328302]

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 NPC109675 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
1.0 High Similarity NPC273772
0.78 Intermediate Similarity NPC27671
0.7647 Intermediate Similarity NPC144418
0.7115 Intermediate Similarity NPC122259
0.7037 Intermediate Similarity NPC173350
0.6481 Remote Similarity NPC73413
0.6415 Remote Similarity NPC472518
0.6271 Remote Similarity NPC50720
0.6182 Remote Similarity NPC253616
0.6034 Remote Similarity NPC472519
0.5862 Remote Similarity NPC31849
0.5862 Remote Similarity NPC85085
0.5636 Remote Similarity NPC472517
0.5614 Remote Similarity NPC471828
0.5614 Remote Similarity NPC229128
0.5517 Remote Similarity NPC54503
0.5517 Remote Similarity NPC472515
0.5439 Remote Similarity NPC271600
0.5424 Remote Similarity NPC472521
0.5424 Remote Similarity NPC213173
0.5397 Remote Similarity NPC472525
0.5333 Remote Similarity NPC61499
0.5333 Remote Similarity NPC471826
0.5192 Remote Similarity NPC123127
0.5063 Remote Similarity NPC471825
0.5063 Remote Similarity NPC604667

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC109675 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