Natural Product: NPC241341

Natural Product IDNPC241341
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-[(2E)-3,7-Dimethylocta-2,6-Dienoxy]-6-Methoxychromen-2-One
IUPAC Name 7-[(2E)-3,7-dimethylocta-2,6-dienoxy]-6-methoxychromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2346913
PubChem CID 5319406
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones

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 NLNMITFNBJXRRP-XNTDXEJSSA-N
Standard InCHI InChI=1S/C20H24O4/c1-14(2)6-5-7-15(3)10-11-23-19-13-17-16(12-18(19)22-4)8-9-20(21)24-17/h6,8-10,12-13H,5,7,11H2,1-4H3/b15-10+
SMILES CC(=CCC/C(=C/COc1cc2c(ccc(=O)o2)cc1OC)/C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.17 Volume:   354.069
?
Van der Waals volume.
Dense:   0.927 LogP:   4.808
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.947
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.054
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   14.0
TPSA:   48.67
?
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:   0.537 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.543 Fsp3:   0.35
MCE-18:   13.0
?
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:   0.681 Fluc inhibitor:   0.412
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.969
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.619
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.488 Promiscuous compounds:   0.029

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.554 MDCK Permeability:   -4.558
Pgp-inhibitor:   0.174 Pgp-substrate:   0.001
PAMPA:   0.023
?
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%):   0.815 30% Bioavailability (F30%):   0.968
50% Bioavailability (F50%):   0.881

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.977
Plasma Protein Binding (PPB):   96.203% Volume Distribution (VD):   -0.057
Fu: 3.536%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.044
BSEP inhibitor:   0.932

ADMET: Metabolism

CYP1A2-inhibitor:   0.331 CYP1A2-substrate:   0.533
CYP2C19-inhibitor:   0.981 CYP2C19-substrate:   0.011
CYP2C9-inhibitor:   0.109 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.804 CYP2D6-substrate:   0.792
CYP3A4-inhibitor:   0.373 CYP3A4-substrate:   0.951
CYP2B6-substrate:   0.012 CYP2C8-inhibitor:   0.996
HLM stability:   0.828
?
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):  6.692 Half-life (T1/2):  0.886

ADMET: Toxicity

hERG Blockers:  0.222 hERG Blockers (10um):  0.494
Human Hepatotoxicity (H-HT):  0.568 Drug-induced Liver Injury (DILI):  0.723
AMES Toxicity:  0.271 Rat Oral Acute Toxicity:  0.311
Maximum Recommended Daily Dose:  0.484 Skin Sensitization:  0.705
Carcinogencity:  0.663 Eye Corrosion:  0.009
Eye Irritation:  0.815 Respiratory Toxicity:  0.841
Drug-induced Neurotoxicity:  0.455 Ototoxicity:  0.284
Hematotoxicity:  0.371 Drug-induced Nephrotoxicity:  0.266
Genotoxicity:  0.722 RPMI-8226 Immunitoxicity:  0.091
A549 Cytotoxicity:  0.098 Hek293 Cytotoxicity:  0.199
BCF:   1.952
?
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:   4.604
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.94
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.587
?
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
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. twig n.a. PMID[10757740]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. flower n.a. PMID[10757740]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[10757740]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. leaf n.a. PMID[10757740]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota leaves n.a. n.a. PMID[18760601]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. bark n.a. PMID[21875114]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[23434131]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. fruit n.a. PMID[23872723]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. fruit n.a. PMID[26247834]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[30579794]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[31302251]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[32996318]
NPO18681 Artemisia scoparia Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[38538562]
NPO18681 Artemisia scoparia Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[38542997]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18681 Artemisia scoparia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2629 Cystoseira caespitosa Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1117 Hypholoma capnoides Species Strophariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24248.1 Lactarius deliciosus var. deterrimus Varieties Russulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9366 Rosa transmorrisonensis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18681 Artemisia scoparia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18681 Artemisia scoparia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21771 Citrus trifoliata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18681 Artemisia scoparia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5045 Aegle marmelos 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]
NPO2629 Cystoseira caespitosa Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9366 Rosa transmorrisonensis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24248.1 Lactarius deliciosus var. deterrimus Varieties Russulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18681 Artemisia scoparia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1117 Hypholoma capnoides Species Strophariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21771 Citrus trifoliata Species Rutaceae 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
NPT1746 Individual protein LXR-beta Homo sapiens Activity n.a. n.a. n.a. PMID[36529937]
NPT106 Individual protein Peroxisome proliferator-activated receptor delta Homo sapiens Activity n.a. n.a. n.a. PMID[36529937]
NPT866 Individual protein Peroxisome proliferator-activated receptor alpha Homo sapiens Activity n.a. n.a. n.a. PMID[36529937]
NPT540 Individual protein Bile acid receptor FXR Homo sapiens Activity n.a. n.a. n.a. PMID[36529937]
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens EC50 > 30000.0 nM PMID[36529937]
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens Ki = 10700.0 nM PMID[36529937]
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens EC50 = 17300.0 nM PMID[36529937]
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens Activity n.a. n.a. n.a. PMID[36529937]
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens EC50 = 25800.0 nM PMID[36529937]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT22409 Protein complex Mitochondrial complex I (NADH dehydrogenase) Homo sapiens IC50 = 24200.0 nM PMID[23434131]
NPT22409 Protein complex Mitochondrial complex I (NADH dehydrogenase) Homo sapiens IC50 = 17500.0 nM PMID[23434131]
NPT2 Others Unspecified n.a. Inhibition = 30.0 % PMID[23434131]
NPT28949 Cell line Mesenchymal stem cells Homo sapiens Activity n.a. n.a. n.a. PMID[36529937]

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 NPC241341 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
0.8644 High Similarity NPC164148
0.8644 High Similarity NPC43500
0.7963 Intermediate Similarity NPC137669
0.7049 Intermediate Similarity NPC180006
0.6984 Remote Similarity NPC233018
0.6935 Remote Similarity NPC19242
0.6825 Remote Similarity NPC235190
0.6462 Remote Similarity NPC290764
0.5926 Remote Similarity NPC240722
0.5833 Remote Similarity NPC258567
0.5694 Remote Similarity NPC267336
0.5694 Remote Similarity NPC272650
0.5571 Remote Similarity NPC216092
0.5493 Remote Similarity NPC191104
0.5443 Remote Similarity NPC469449
0.5397 Remote Similarity NPC309953
0.5352 Remote Similarity NPC2363
0.5352 Remote Similarity NPC479429
0.5352 Remote Similarity NPC29734
0.5352 Remote Similarity NPC479314
0.5342 Remote Similarity NPC193881
0.5342 Remote Similarity NPC601639
0.5323 Remote Similarity NPC281356
0.5286 Remote Similarity NPC479428
0.5286 Remote Similarity NPC121740
0.5286 Remote Similarity NPC113098
0.5075 Remote Similarity NPC606257
0.507 Remote Similarity NPC224774

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC241341 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