Natural Product: NPC469978

Natural Product IDNPC469978
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sid14737105
IUPAC Name 1-(1,3-benzodioxol-5-yl)-3-piperidin-1-ylpropan-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1606959
PubChem CID 147354
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 DJXZMJWCDITTEO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H19NO3/c17-13(6-9-16-7-2-1-3-8-16)12-4-5-14-15(10-12)19-11-18-14/h4-5,10H,1-3,6-9,11H2
SMILES O=C(c1ccc2c(c1)OCO2)CCN1CCCCC1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   261.14 Volume:   269.148
?
Van der Waals volume.
Dense:   0.97 LogP:   2.591
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.561
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.537
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   17.0
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:   0.78 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.955 Fsp3:   0.533
MCE-18:   35.304
?
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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.097 Fluc inhibitor:   0.027
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.143
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.246
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.005 Promiscuous compounds:   0.499

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.496 MDCK Permeability:   -4.884
Pgp-inhibitor:   0.013 Pgp-substrate:   0.005
PAMPA:   0.312
?
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):   0.0
20% Bioavailability (F20%):   0.046 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.329

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.992 MRP1:   0.422
Plasma Protein Binding (PPB):   82.388% Volume Distribution (VD):   0.806
Fu: 16.994%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.603
OATP1B3 inhibitor:   0.96 BCRP inhibitor:   0.004
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.067 CYP2C19-substrate:   0.053
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.987
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.003
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.006
HLM stability:   0.854
?
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):  6.891 Half-life (T1/2):  1.278

ADMET: Toxicity

hERG Blockers:  0.641 hERG Blockers (10um):  0.649
Human Hepatotoxicity (H-HT):  0.429 Drug-induced Liver Injury (DILI):  0.168
AMES Toxicity:  0.364 Rat Oral Acute Toxicity:  0.504
Maximum Recommended Daily Dose:  0.656 Skin Sensitization:  0.613
Carcinogencity:  0.477 Eye Corrosion:  0.035
Eye Irritation:  0.28 Respiratory Toxicity:  0.942
Drug-induced Neurotoxicity:  0.925 Ototoxicity:  0.184
Hematotoxicity:  0.355 Drug-induced Nephrotoxicity:  0.554
Genotoxicity:  0.335 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.085 Hek293 Cytotoxicity:  0.49
BCF:   0.835
?
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:   3.433
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.868
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.245
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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
NPT3 Individual protein Thioredoxin glutathione reductase Schistosoma mansoni Potency = 281.8 nM PMID[12617583]
NPT151 Individual protein 15-hydroxyprostaglandin dehydrogenase [NAD+] Homo sapiens Potency = 35481.3 nM PMID[22608855]
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 44668.4 nM Open TG-GATES in vivo data: Biochemistry
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 11220.2 nM PMID[19762244]
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 31622.8 nM PMID[21036050]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 25118.9 nM PMID[19124661]
NPT1043 Individual protein Glycoprotein hormones alpha chain Homo sapiens Potency n.a. 5623.4 nM PubChem BioAssay data set
NPT159 Individual protein Aberrant vpr protein Human immunodeficiency virus 1 Potency n.a. 7943.3 nM PMID[20441162]
NPT261 Individual protein Monoamine oxidase A Homo sapiens IC50 > 100000.0 nM PMID[20627740]
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 12589.3 nM PMID[10346950]
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 3162.3 nM PMID[17132069]
NPT582 Individual protein Monoamine oxidase B Homo sapiens IC50 = 3430.0 nM PMID[23819826]
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 25.1 nM PMID[25372480]
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 316.2 nM PubChem BioAssay data set
NPT698 Individual protein Regulator of G-protein signaling 4 Homo sapiens Potency n.a. 44668.4 nM DOI[10.1021/np9606815]
NPT888 Individual protein 78 kDa glucose-regulated protein Homo sapiens Potency n.a. 44668.4 nM PMID[18625769]
NPT831 Individual protein Serine/threonine-protein kinase PLK1 Homo sapiens Potency n.a. 21192.3 nM PMID[19586051]
NPT821 Individual protein Werner syndrome ATP-dependent helicase Homo sapiens Potency n.a. 50118.7 nM PMID[18163588]
NPT53 Individual protein 4'-phosphopantetheinyl transferase ffp Bacillus subtilis Potency = 56234.1 nM DrugMatrix in vitro pharmacology data
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 7943.3 nM PMID[24467317]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Potency n.a. 17782.8 nM PubChem BioAssay data set
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa Inhibition = 26.26 % DOI[10.6019/CHEMBL4513160]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa Inhibition = 2.18 % DOI[10.6019/CHEMBL4513160]
NPT2 Others Unspecified n.a. Potency = 11582.1 nM PMID[19627125]
NPT747 Organism Acinetobacter baumannii Acinetobacter baumannii Inhibition = -1.3 % DOI[10.6019/CHEMBL4513160]

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 NPC469978 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
0.7234 Intermediate Similarity NPC470088
0.6047 Remote Similarity NPC286683
0.5192 Remote Similarity NPC327052

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC469978 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
0.5283 Remote Similarity NPD3142 Phase 4
0.5185 Remote Similarity NPD3140 Approved

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