Natural Product: NPC80170

Natural Product IDNPC80170
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 8-(3,3-Dimethyl-Oxiranylmethyl)-7-Methoxy-Chromen-2-One
IUPAC Name 8-[(3,3-dimethyloxiran-2-yl)methyl]-7-methoxychromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL52267
PubChem CID 3819217
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 LSZONYLDFHGRDP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H16O4/c1-15(2)12(19-15)8-10-11(17-3)6-4-9-5-7-13(16)18-14(9)10/h4-7,12H,8H2,1-3H3
SMILES CC1(C)C(Cc2c(ccc3ccc(=O)oc23)OC)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.1 Volume:   264.305
?
Van der Waals volume.
Dense:   0.984 LogP:   2.475
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.57
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.77
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   15.0
TPSA:   51.97
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.628 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.103 Fsp3:   0.4
MCE-18:   57.429
?
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:   0.168 Fluc inhibitor:   0.027
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.989
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.425
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.448 Promiscuous compounds:   0.502

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.425 MDCK Permeability:   -4.532
Pgp-inhibitor:   0.028 Pgp-substrate:   0.0
PAMPA:   0.23
?
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%):   0.803 30% Bioavailability (F30%):   0.415
50% Bioavailability (F50%):   0.551

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.998
Plasma Protein Binding (PPB):   85.961% Volume Distribution (VD):   0.238
Fu: 13.799%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.965 CYP1A2-substrate:   0.061
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.019
CYP2C9-inhibitor:   0.934 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.055 CYP2D6-substrate:   0.989
CYP3A4-inhibitor:   0.987 CYP3A4-substrate:   0.737
CYP2B6-substrate:   0.993 CYP2C8-inhibitor:   0.764
HLM stability:   0.848
?
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):  8.859 Half-life (T1/2):  0.734

ADMET: Toxicity

hERG Blockers:  0.166 hERG Blockers (10um):  0.442
Human Hepatotoxicity (H-HT):  0.548 Drug-induced Liver Injury (DILI):  0.839
AMES Toxicity:  0.665 Rat Oral Acute Toxicity:  0.491
Maximum Recommended Daily Dose:  0.715 Skin Sensitization:  0.435
Carcinogencity:  0.75 Eye Corrosion:  0.206
Eye Irritation:  0.944 Respiratory Toxicity:  0.798
Drug-induced Neurotoxicity:  0.515 Ototoxicity:  0.204
Hematotoxicity:  0.282 Drug-induced Nephrotoxicity:  0.217
Genotoxicity:  0.826 RPMI-8226 Immunitoxicity:  0.074
A549 Cytotoxicity:  0.066 Hek293 Cytotoxicity:  0.362
BCF:   1.229
?
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:   3.878
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.165
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.706
?
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
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11240-011-0014-8]
NPO27288 Citrus maxima Species Rutaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(99)00119-3]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[10606602]
NPO5270 Citrus natsudaidai Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[17689080]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[35268681]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36365393]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36840093]
NPO27288 Citrus maxima Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[37049761]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[37959863]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[38308284]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38370080]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[39141828]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[39401641]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[39410132]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[39633960]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5270 Citrus natsudaidai Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27288 Citrus maxima Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31056 Mentha haplocalyx Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16308 Citrus wilsonii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO27288 Citrus maxima Species Rutaceae Eukaryota n.a. n.a. Database[FooDB]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO30828 Mentha piperita Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16308 Citrus wilsonii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31056 Mentha haplocalyx Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO27288 Citrus maxima Species Rutaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO4109 Exocarpium citri grandis n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27288 Citrus maxima Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16308 Citrus wilsonii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16308 Citrus wilsonii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31056 Mentha haplocalyx Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5270 Citrus natsudaidai Species Rutaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO16308 Citrus wilsonii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5270 Citrus natsudaidai Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27288 Citrus maxima Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16308 Citrus wilsonii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27288 Citrus maxima Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5270 Citrus natsudaidai Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7317 Citrus aurantium 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT3171 Cell line V79 Cricetulus griseus IC50 > 100000.0 nM DOI[10.1016/0960-894X(96)00315-0]

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 NPC80170 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
0.717 Intermediate Similarity NPC168710
0.6863 Remote Similarity NPC55147
0.6863 Remote Similarity NPC96286
0.6786 Remote Similarity NPC472424
0.6786 Remote Similarity NPC281241
0.6604 Remote Similarity NPC62366
0.6604 Remote Similarity NPC185066
0.6604 Remote Similarity NPC33986
0.6441 Remote Similarity NPC55149
0.6441 Remote Similarity NPC260265
0.6296 Remote Similarity NPC188380
0.6296 Remote Similarity NPC224543
0.6111 Remote Similarity NPC104796
0.6 Remote Similarity NPC87950
0.6 Remote Similarity NPC479311
0.5893 Remote Similarity NPC199204
0.5741 Remote Similarity NPC175159
0.5714 Remote Similarity NPC485014
0.5636 Remote Similarity NPC472516
0.5636 Remote Similarity NPC271600
0.5625 Remote Similarity NPC485015
0.5593 Remote Similarity NPC479313
0.5556 Remote Similarity NPC479310
0.5536 Remote Similarity NPC50896
0.5536 Remote Similarity NPC229916
0.5536 Remote Similarity NPC326600
0.5536 Remote Similarity NPC122259
0.5536 Remote Similarity NPC610664
0.5469 Remote Similarity NPC479308
0.5424 Remote Similarity NPC605506
0.5333 Remote Similarity NPC153818
0.5333 Remote Similarity NPC232246
0.5323 Remote Similarity NPC479312
0.5263 Remote Similarity NPC225106
0.5263 Remote Similarity NPC13007
0.5263 Remote Similarity NPC184861
0.5263 Remote Similarity NPC281014
0.5263 Remote Similarity NPC212124
0.5263 Remote Similarity NPC294456
0.5254 Remote Similarity NPC270256
0.5246 Remote Similarity NPC167111
0.5246 Remote Similarity NPC318400
0.5238 Remote Similarity NPC469675
0.5161 Remote Similarity NPC26954
0.5161 Remote Similarity NPC38099
0.5079 Remote Similarity NPC479309
0.5077 Remote Similarity NPC129572
0.5075 Remote Similarity NPC484110

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC80170 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