Natural Product: NPC183648

Natural Product IDNPC183648
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 P-Methoxy-Acetophenone
IUPAC Name 1-(4-methoxyphenyl)ethanone
Synonyms 1-(4-Methoxyphenyl)Ethanone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL401912
PubChem CID 7476
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0003670] Aryl ketones
              • [CHEMONTID:0004296] Phenylketones
                • [CHEMONTID:0004298] Alkyl-phenylketones

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 NTPLXRHDUXRPNE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C9H10O2/c1-7(10)8-3-5-9(11-2)6-4-8/h3-6H,1-2H3
SMILES COc1ccc(cc1)C(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   150.07 Volume:   162.698
?
Van der Waals volume.
Dense:   0.922 LogP:   1.744
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.95
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.112
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   7.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.602 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.206 Fsp3:   0.222
MCE-18:   6.0
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.072 Fluc inhibitor:   0.037
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.009
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.014
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   1.0 Promiscuous compounds:   0.067

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.489 MDCK Permeability:   -4.518
Pgp-inhibitor:   0.466 Pgp-substrate:   0.121
PAMPA:   0.098
?
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):   0.21
20% Bioavailability (F20%):   0.255 30% Bioavailability (F30%):   0.362
50% Bioavailability (F50%):   0.729

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.344 MRP1:   0.352
Plasma Protein Binding (PPB):   77.837% Volume Distribution (VD):   -0.038
Fu: 18.922%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.929
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.379
BSEP inhibitor:   0.688

ADMET: Metabolism

CYP1A2-inhibitor:   0.949 CYP1A2-substrate:   0.929
CYP2C19-inhibitor:   0.215 CYP2C19-substrate:   0.505
CYP2C9-inhibitor:   0.014 CYP2C9-substrate:   0.081
CYP2D6-inhibitor:   0.137 CYP2D6-substrate:   0.031
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.004 CYP2C8-inhibitor:   0.804
HLM stability:   0.994
?
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):  9.716 Half-life (T1/2):  0.914

ADMET: Toxicity

hERG Blockers:  0.144 hERG Blockers (10um):  0.45
Human Hepatotoxicity (H-HT):  0.421 Drug-induced Liver Injury (DILI):  0.49
AMES Toxicity:  0.56 Rat Oral Acute Toxicity:  0.172
Maximum Recommended Daily Dose:  0.19 Skin Sensitization:  0.411
Carcinogencity:  0.691 Eye Corrosion:  0.842
Eye Irritation:  0.994 Respiratory Toxicity:  0.702
Drug-induced Neurotoxicity:  0.613 Ototoxicity:  0.22
Hematotoxicity:  0.484 Drug-induced Nephrotoxicity:  0.348
Genotoxicity:  0.161 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.054 Hek293 Cytotoxicity:  0.153
BCF:   0.507
?
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:   2.865
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.656
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.035
?
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
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. leaf n.a. DOI[10.1016/S0031-9422(00)94055-X]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. flower n.a. DOI[10.3390/70200245]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[11076555]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota Roots n.a. n.a. PMID[11459643]
NPO32889 baccharis sp. Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[11929285]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[1517743]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. root n.a. PMID[17238120]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. root n.a. PMID[18405608]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. root n.a. PMID[18661821]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21417376]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21627108]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[24617303]
NPO47860 Gonystylus bancanus Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[37709800]
NPO47860 Gonystylus bancanus Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[38802441]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. root n.a. PMID[7700984]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[8277318]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO32889 baccharis sp. Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11391 Polygonum cuspidatum Species Polygonaceae 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]
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]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO22273 Angelica pubescens Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17752 Mentha X piperita Strain Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22273 Angelica pubescens Species Apiaceae 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
NPO17752 Mentha X piperita Other Leaf 0.0055 0.001 0.01 mg/100g Database [DUKE]
NPO47860 Gonystylus bancanus n-hexane extract n.a. 0.51 n.a. n.a. % PMID[37709800]
NPO47860 Gonystylus bancanus Dichloro methane extract n.a. 0.41 n.a. n.a. % PMID[37709800]
NPO47860 Gonystylus bancanus Ethyl acetate extract n.a. 0.17 n.a. n.a. % PMID[37709800]

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
NPT590 Individual protein 3-alpha-hydroxysteroid dehydrogenase Rattus norvegicus Ratio = 0.97 uL/min PMID[18006320]
NPT43 Individual protein Tyrosinase Agaricus bisporus IC50 = 2000000.0 nM PMID[18326070]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = 47.2 % PMID[18326070]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT597 Organism Spinacia oleracea Spinacia oleracea IC50 = 65700.0 nM PMID[11929285]
NPT595 Organism Physalis ixocarpa Physalis ixocarpa IC50 = 54600.0 nM PMID[11929285]
NPT364 Organism Lactuca sativa Lactuca sativa IC50 = 55900.0 nM PMID[11929285]
NPT595 Organism Physalis ixocarpa Physalis ixocarpa IC50 = 20500.0 nM PMID[11929285]
NPT595 Organism Physalis ixocarpa Physalis ixocarpa IC50 = 20100.0 nM PMID[11929285]
NPT364 Organism Lactuca sativa Lactuca sativa IC50 = 44300.0 nM PMID[11929285]
NPT364 Organism Lactuca sativa Lactuca sativa IC50 = 49500.0 nM PMID[11929285]
NPT364 Organism Lactuca sativa Lactuca sativa GI50 = 51200.0 nM PMID[11929285]
NPT595 Organism Physalis ixocarpa Physalis ixocarpa GI50 = 23500.0 nM PMID[11929285]
NPT596 Organism Lolium multiflorum Lolium multiflorum IC50 = 40000.0 nM PMID[11929285]
NPT596 Organism Lolium multiflorum Lolium multiflorum IC50 = 18900.0 nM PMID[11929285]
NPT596 Organism Lolium multiflorum Lolium multiflorum IC50 = 17900.0 nM PMID[11929285]
NPT596 Organism Lolium multiflorum Lolium multiflorum GI50 = 18100.0 nM PMID[11929285]
NPT2 Others Unspecified n.a. Potency n.a. 22548.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 44600.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 28141.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 566.4 nM PubChem BioAssay data set
NPT355 Organism Phaseolus vulgaris Phaseolus vulgaris IC50 = 151800.0 nM PMID[11929285]
NPT594 Organism Trifolium pratense Trifolium pratense IC50 = 57600.0 nM PMID[11929285]
NPT594 Organism Trifolium pratense Trifolium pratense IC50 = 126200.0 nM PMID[11929285]
NPT594 Organism Trifolium pratense Trifolium pratense IC50 = 120000.0 nM PMID[11929285]
NPT594 Organism Trifolium pratense Trifolium pratense GI50 = 125900.0 nM PMID[11929285]
NPT29131 Unknown Molecular identity unknown n.a. Activity = 24.6 nmol/min/mg PMID[36966660]
NPT29131 Unknown Molecular identity unknown n.a. Activity = 221.0 nmol/min/mg PMID[36966660]

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 NPC183648 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
0.72 Intermediate Similarity NPC23332
0.68 Remote Similarity NPC470860
0.6538 Remote Similarity NPC258425
0.5862 Remote Similarity NPC469954
0.5833 Remote Similarity NPC57879
0.5833 Remote Similarity NPC177844
0.5769 Remote Similarity NPC166591
0.5714 Remote Similarity NPC45249
0.5556 Remote Similarity NPC71853
0.5517 Remote Similarity NPC251306
0.5357 Remote Similarity NPC321956
0.5357 Remote Similarity NPC99886
0.5357 Remote Similarity NPC38209
0.5357 Remote Similarity NPC259134
0.5357 Remote Similarity NPC8002
0.5333 Remote Similarity NPC474691
0.5333 Remote Similarity NPC186098
0.5333 Remote Similarity NPC225245
0.5238 Remote Similarity NPC23837
0.5217 Remote Similarity NPC2785
0.5185 Remote Similarity NPC305205

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC183648 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
0.5625 Remote Similarity NPD3972 Phase 4

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