Natural Product: NPC231717

Natural Product IDNPC231717
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1-(4-Hydroxy-2-Methylphenyl)Ethanone
IUPAC Name 1-(4-hydroxy-2-methylphenyl)ethanone
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL47807
PubChem CID 70133
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 IAMNVCJECQWBLZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C9H10O2/c1-6-5-8(11)3-4-9(6)7(2)10/h3-5,11H,1-2H3
SMILES Oc1ccc(c(c1)C)C(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   150.07 Volume:   162.698
?
Van der Waals volume.
Dense:   0.922 LogP:   2.0
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.775
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.906
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   7.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.621 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.808 Fsp3:   0.222
MCE-18:   7.0
?
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:   0.048 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.079
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.997 Promiscuous compounds:   0.05

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.507 MDCK Permeability:   -4.55
Pgp-inhibitor:   0.068 Pgp-substrate:   0.162
PAMPA:   0.546
?
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):   0.023
20% Bioavailability (F20%):   0.207 30% Bioavailability (F30%):   0.21
50% Bioavailability (F50%):   0.771

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.271 MRP1:   0.63
Plasma Protein Binding (PPB):   90.155% Volume Distribution (VD):   -0.262
Fu: 10.139%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.879
OATP1B3 inhibitor:   0.96 BCRP inhibitor:   0.211
BSEP inhibitor:   0.235

ADMET: Metabolism

CYP1A2-inhibitor:   0.948 CYP1A2-substrate:   0.985
CYP2C19-inhibitor:   0.539 CYP2C19-substrate:   0.834
CYP2C9-inhibitor:   0.009 CYP2C9-substrate:   0.126
CYP2D6-inhibitor:   0.48 CYP2D6-substrate:   0.343
CYP3A4-inhibitor:   0.272 CYP3A4-substrate:   0.72
CYP2B6-substrate:   0.013 CYP2C8-inhibitor:   0.955
HLM stability:   0.981
?
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):  6.156 Half-life (T1/2):  0.971

ADMET: Toxicity

hERG Blockers:  0.095 hERG Blockers (10um):  0.495
Human Hepatotoxicity (H-HT):  0.47 Drug-induced Liver Injury (DILI):  0.221
AMES Toxicity:  0.473 Rat Oral Acute Toxicity:  0.186
Maximum Recommended Daily Dose:  0.283 Skin Sensitization:  0.727
Carcinogencity:  0.668 Eye Corrosion:  0.929
Eye Irritation:  0.998 Respiratory Toxicity:  0.641
Drug-induced Neurotoxicity:  0.504 Ototoxicity:  0.2
Hematotoxicity:  0.319 Drug-induced Nephrotoxicity:  0.12
Genotoxicity:  0.371 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.076 Hek293 Cytotoxicity:  0.277
BCF:   0.664
?
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:   2.983
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.058
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.271
?
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
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. Nigeria(latitude 80°N and longitude 4°E) 2005; 2006 DOI[10.1002/ejlt.201000080]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11240-015-0761-z]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11306-010-0259-y]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11306-014-0638-x]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11746-997-0093-1]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s12010-013-0354-4]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.phytol.2008.07.007]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Seeds Plovdiv, Plovdiv region in South Bulgaria DOI[10.1051/CTV/20163101031]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1055/S-2006-958077]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. DOI[10.1111/j.1399-3054.2000.1100409.x]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1186/s40064-015-0831-z]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1501/Tarimbil_0000001065]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[11170689]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. leaf n.a. PMID[11312782]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. fruit n.a. PMID[11312782]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[11408943]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. fruit n.a. PMID[12105962]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. Esuela Tecnica Superior de Ingenieros Agrónomos de Albacete 2007 PMID[19256538]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[20826702]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. xylem n.a. PMID[21348469]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[22537213]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[23759170]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Stalks n.a. n.a. PMID[24521157]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Seeds Benedictine Pannonhalma Archabbey, Hungary PMID[29803478]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[31433178]
NPO46827 Alhagi mannifera Genus Fabaceae Eukaryota n.a. n.a. n.a. PMID[34384010]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. PMID[3735324]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[37446586]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[37570937]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Fruits n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Leaf Essent. Oil n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17024 Vitis vinifera Species Vitaceae 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
NPO46827 Alhagi mannifera n.a. n.a. 0.71 n.a. n.a. % PMID[34384010]

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
NPT5340 Protein family Inosine-5'-monophosphate dehydrogenase (IMPDH) Homo sapiens IC50 = 620000.0 nM PMID[12729643]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC231717 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
0.6061 Remote Similarity NPC606602
0.5862 Remote Similarity NPC34715
0.5714 Remote Similarity NPC6984
0.5333 Remote Similarity NPC240163
0.5278 Remote Similarity NPC486398
0.5161 Remote Similarity NPC91478
0.5161 Remote Similarity NPC161617
0.5143 Remote Similarity NPC600864
0.5135 Remote Similarity NPC486397

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC231717 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