Natural Product: NPC309982

Natural Product IDNPC309982
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-Methoxybenzaldehyde Oxime
IUPAC Name (NE)-N-[(4-methoxyphenyl)methylidene]hydroxylamine
Synonyms 4-Methoxy-Benzaldehyde Oxime
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL172979
PubChem CID 5371961
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002341] Phenol ethers
        • [CHEMONTID:0000138] Anisoles

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 FXOSHPAYNZBSFO-RMKNXTFCSA-N
Standard InCHI InChI=1S/C8H9NO2/c1-11-8-4-2-7(3-5-8)6-9-10/h2-6,10H,1H3/b9-6+
SMILES COc1ccc(cc1)/C=N/O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   151.06 Volume:   156.399
?
Van der Waals volume.
Dense:   0.966 LogP:   1.949
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.118
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.586
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   7.0
TPSA:   41.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.395 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.814 Fsp3:   0.125
MCE-18:   5.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.008 Fluc inhibitor:   0.961
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.03
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.048
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.633 Promiscuous compounds:   0.429

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.137 MDCK Permeability:   -4.705
Pgp-inhibitor:   0.788 Pgp-substrate:   0.0
PAMPA:   0.048
?
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):   0.378
20% Bioavailability (F20%):   0.894 30% Bioavailability (F30%):   0.957
50% Bioavailability (F50%):   0.939

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.0
Plasma Protein Binding (PPB):   77.218% Volume Distribution (VD):   -0.848
Fu: 19.276%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.968
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.044
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.074
CYP2C9-inhibitor:   0.027 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.436 CYP2D6-substrate:   0.148
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.988
HLM stability:   0.007
?
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):  5.514 Half-life (T1/2):  0.852

ADMET: Toxicity

hERG Blockers:  0.129 hERG Blockers (10um):  0.408
Human Hepatotoxicity (H-HT):  0.627 Drug-induced Liver Injury (DILI):  0.783
AMES Toxicity:  0.468 Rat Oral Acute Toxicity:  0.322
Maximum Recommended Daily Dose:  0.066 Skin Sensitization:  0.934
Carcinogencity:  0.39 Eye Corrosion:  0.938
Eye Irritation:  0.997 Respiratory Toxicity:  0.915
Drug-induced Neurotoxicity:  0.807 Ototoxicity:  0.279
Hematotoxicity:  0.341 Drug-induced Nephrotoxicity:  0.648
Genotoxicity:  0.103 RPMI-8226 Immunitoxicity:  0.058
A549 Cytotoxicity:  0.07 Hek293 Cytotoxicity:  0.066
BCF:   1.154
?
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:   3.549
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.169
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.579
?
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]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[10869194]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota leaves n.a. n.a. PMID[18588343]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[19331340]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. aerial part n.a. PMID[21070010]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[21070010]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[24617303]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[27700077]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[28225280]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[31789520]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[31804070]
NPO13274 Illicium verum Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[38790803]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13274 Illicium verum Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29352 Uncaria sinensis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13274 Illicium verum Species Schisandraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO13274 Illicium verum Species Schisandraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO13274 Illicium verum Species Schisandraceae Eukaryota n.a. n.a. Database[FooDB]
NPO13274 Illicium verum Species Schisandraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO29352 Uncaria sinensis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13274 Illicium verum Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. pericarp n.a. PMID[p25172756]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29352 Uncaria sinensis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13274 Illicium verum Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13274 Illicium verum Species Schisandraceae 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]
NPO29352 Uncaria sinensis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14112 Uncaria rhynchophylla Species Rubiaceae 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]
NPO29352 Uncaria sinensis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13274 Illicium verum Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13274 Illicium verum Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28295 Foeniculum vulgare Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29352 Uncaria sinensis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13989 Uncaria macrophylla Species Rubiaceae 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
NPT270 Individual protein Nitric oxide synthase, inducible Mus musculus NOHA < 0.2 % PMID[11831907]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Activity = 7.6 % PMID[23916150]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Inhibition = 4.0 % PMID[23916150]

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 NPC309982 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
0.68 Remote Similarity NPC57879
0.5357 Remote Similarity NPC125144

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC309982 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