Natural Product: NPC186097

Natural Product IDNPC186097
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1-(2-Hydroxy-6-Methoxyphenyl)-9-(4-Hydroxyphenyl)Nonan-1-One
IUPAC Name 1-(2-hydroxy-6-methoxyphenyl)-9-(4-hydroxyphenyl)nonan-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL491789
PubChem CID 13965861
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 RIAGDOZDWVDTRR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H28O4/c1-26-21-12-8-11-20(25)22(21)19(24)10-7-5-3-2-4-6-9-17-13-15-18(23)16-14-17/h8,11-16,23,25H,2-7,9-10H2,1H3
SMILES COc1cccc(c1C(=O)CCCCCCCCc1ccc(cc1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.2 Volume:   388.661
?
Van der Waals volume.
Dense:   0.916 LogP:   4.399
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.205
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.971
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   13.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.425 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.066 Fsp3:   0.409
MCE-18:   12.0
?
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:   0.675 Fluc inhibitor:   0.532
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.054
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.501
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.388 Promiscuous compounds:   0.111

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.988 MDCK Permeability:   -4.707
Pgp-inhibitor:   0.019 Pgp-substrate:   0.214
PAMPA:   0.233
?
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):   0.009
20% Bioavailability (F20%):   0.162 30% Bioavailability (F30%):   0.411
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.045 MRP1:   0.878
Plasma Protein Binding (PPB):   99.041% Volume Distribution (VD):   0.21
Fu: 0.479%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.973
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.529
BSEP inhibitor:   0.972

ADMET: Metabolism

CYP1A2-inhibitor:   0.589 CYP1A2-substrate:   0.983
CYP2C19-inhibitor:   0.095 CYP2C19-substrate:   0.975
CYP2C9-inhibitor:   0.43 CYP2C9-substrate:   0.362
CYP2D6-inhibitor:   0.987 CYP2D6-substrate:   0.983
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.554
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.962
?
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):  5.235 Half-life (T1/2):  0.475

ADMET: Toxicity

hERG Blockers:  0.396 hERG Blockers (10um):  0.805
Human Hepatotoxicity (H-HT):  0.455 Drug-induced Liver Injury (DILI):  0.101
AMES Toxicity:  0.259 Rat Oral Acute Toxicity:  0.192
Maximum Recommended Daily Dose:  0.332 Skin Sensitization:  0.871
Carcinogencity:  0.263 Eye Corrosion:  0.323
Eye Irritation:  0.992 Respiratory Toxicity:  0.872
Drug-induced Neurotoxicity:  0.261 Ototoxicity:  0.165
Hematotoxicity:  0.108 Drug-induced Nephrotoxicity:  0.318
Genotoxicity:  0.003 RPMI-8226 Immunitoxicity:  0.071
A549 Cytotoxicity:  0.621 Hek293 Cytotoxicity:  0.719
BCF:   2.028
?
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:   5.701
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.533
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.217
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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
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota seeds n.a. n.a. PMID[17998162]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[1955885]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. fruit n.a. PMID[20879744]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[27419473]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[32515616]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[33444950]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Leaf Essent. Oil n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Aril n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5241 Myristica fragrans Species Myristicaceae 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
NPT589 Individual protein Serum albumin Bos taurus IC50 = 104270.0 nM PMID[29789207]
NPT3809 Individual protein Pancreatic alpha-amylase Sus scrofa IC50 = 32270.0 nM PMID[29789207]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT839 Cell line L6 Rattus norvegicus Activity = 18.3 % PMID[29789207]
NPT839 Cell line L6 Rattus norvegicus Activity = 34.1 % PMID[29789207]
NPT839 Cell line L6 Rattus norvegicus Activity = 34.6 % PMID[29789207]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 4.0 ug.mL-1 PubChem BioAssay data set
NPT20 Organism Candida albicans Candida albicans MIC < 32.0 ug.mL-1 PMID[25322455]
NPT3730 Organism Enterococcus durans Enterococcus durans MIC = 2.0 ug.mL-1 PMID[23964704]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 4.0 ug.mL-1 PMID[23102654]
NPT3730 Organism Enterococcus durans Enterococcus durans MIC = 4.0 ug.mL-1 PMID[15332848]

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 NPC186097 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
0.84 Intermediate Similarity NPC475009
0.7451 Intermediate Similarity NPC475008
0.6667 Remote Similarity NPC196976
0.5556 Remote Similarity NPC188814
0.5556 Remote Similarity NPC608141
0.5455 Remote Similarity NPC475017
0.5294 Remote Similarity NPC474839
0.5263 Remote Similarity NPC244441
0.5263 Remote Similarity NPC18877
0.5088 Remote Similarity NPC159623

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC186097 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