Natural Product: NPC470707

Natural Product IDNPC470707
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (E)-3-(1,3-Benzodioxol-5-Yl)-1-(4-Methylpiperidin-1-Yl)Prop-2-En-1-One
IUPAC Name (E)-3-(1,3-benzodioxol-5-yl)-1-(4-methylpiperidin-1-yl)prop-2-en-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2203919
PubChem CID 680623
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000296] Benzodioxoles

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 BIXTXZXWPUQSJC-HWKANZROSA-N
Standard InCHI InChI=1S/C16H19NO3/c1-12-6-8-17(9-7-12)16(18)5-3-13-2-4-14-15(10-13)20-11-19-14/h2-5,10,12H,6-9,11H2,1H3/b5-3+
SMILES CC1CCN(CC1)C(=O)C=CC2=CC3=C(C=C2)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   273.14 Volume:   283.808
?
Van der Waals volume.
Dense:   0.962 LogP:   3.182
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.254
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.685
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   38.77
?
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:   0.778 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.151 Fsp3:   0.438
MCE-18:   37.826
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.757 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.448
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.802
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.011 Promiscuous compounds:   0.008

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.745 MDCK Permeability:   -4.585
Pgp-inhibitor:   0.829 Pgp-substrate:   0.067
PAMPA:   0.093
?
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):   0.011
20% Bioavailability (F20%):   0.493 30% Bioavailability (F30%):   0.018
50% Bioavailability (F50%):   0.815

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.859 MRP1:   0.855
Plasma Protein Binding (PPB):   95.704% Volume Distribution (VD):   0.155
Fu: 4.038%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.593
OATP1B3 inhibitor:   0.683 BCRP inhibitor:   0.031
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.03 CYP1A2-substrate:   0.931
CYP2C19-inhibitor:   0.831 CYP2C19-substrate:   0.655
CYP2C9-inhibitor:   0.937 CYP2C9-substrate:   0.212
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.87
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.742
CYP2B6-substrate:   0.258 CYP2C8-inhibitor:   0.167
HLM stability:   0.657
?
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):  4.279 Half-life (T1/2):  0.908

ADMET: Toxicity

hERG Blockers:  0.353 hERG Blockers (10um):  0.555
Human Hepatotoxicity (H-HT):  0.687 Drug-induced Liver Injury (DILI):  0.57
AMES Toxicity:  0.546 Rat Oral Acute Toxicity:  0.229
Maximum Recommended Daily Dose:  0.44 Skin Sensitization:  0.757
Carcinogencity:  0.62 Eye Corrosion:  0.018
Eye Irritation:  0.656 Respiratory Toxicity:  0.607
Drug-induced Neurotoxicity:  0.664 Ototoxicity:  0.349
Hematotoxicity:  0.41 Drug-induced Nephrotoxicity:  0.539
Genotoxicity:  0.475 RPMI-8226 Immunitoxicity:  0.127
A549 Cytotoxicity:  0.167 Hek293 Cytotoxicity:  0.402
BCF:   0.924
?
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:   3.474
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.04
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.439
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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
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. fruit n.a. DOI[10.1016/S0040-4039(01)00209-X]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[10575373]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. leaf n.a. PMID[15467205]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. whole plant n.a. PMID[16808005]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[23102654]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[31096694]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[31103896]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[31766491]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[38067483]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[38474459]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28928 Piper nigrum Species Piperaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. Database[FooDB]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. Database[FooDB]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28928 Piper nigrum Species Piperaceae 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
NPT261 Individual protein Monoamine oxidase A Homo sapiens IC50 > 100000.0 nM PMID[22698782]
NPT582 Individual protein Monoamine oxidase B Homo sapiens IC50 = 497.0 nM PMID[22014827]
NPT589 Individual protein Serum albumin Bos taurus Activity = 50.0 % PMID[20141173]

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 NPC470707 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
0.8222 Intermediate Similarity NPC217574
0.8043 Intermediate Similarity NPC167096
0.8043 Intermediate Similarity NPC605721
0.7 Intermediate Similarity NPC469808
0.6538 Remote Similarity NPC94280
0.6415 Remote Similarity NPC255817
0.6415 Remote Similarity NPC136330
0.6182 Remote Similarity NPC205178
0.6182 Remote Similarity NPC227218
0.6182 Remote Similarity NPC159150
0.614 Remote Similarity NPC103947
0.614 Remote Similarity NPC45783
0.6136 Remote Similarity NPC127326
0.6071 Remote Similarity NPC193673
0.6034 Remote Similarity NPC328419
0.6034 Remote Similarity NPC73883
0.6034 Remote Similarity NPC251454
0.5965 Remote Similarity NPC230698
0.5965 Remote Similarity NPC99078
0.5965 Remote Similarity NPC96406
0.5932 Remote Similarity NPC220923
0.5932 Remote Similarity NPC196609
0.5532 Remote Similarity NPC111225
0.5345 Remote Similarity NPC194359
0.5345 Remote Similarity NPC28641
0.5345 Remote Similarity NPC180647
0.5345 Remote Similarity NPC225745
0.5167 Remote Similarity NPC318862
0.5098 Remote Similarity NPC212643
0.5082 Remote Similarity NPC251466

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470707 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
0.6415 Remote Similarity NPD2492 Phase 2
0.58 Remote Similarity NPD1357 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