Natural Product: NPC531724

Natural Product IDNPC531724
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-(1,3-benzodioxol-5-yl)-1-(1-piperidyl)hepta-2,4-dien-1-one
IUPAC Name 7-(1,3-benzodioxol-5-yl)-1-(1-piperidyl)hepta-2,4-dien-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 FNECAUUPWFQEGF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H23NO3/c21-19(20-12-6-3-7-13-20)9-5-2-1-4-8-16-10-11-17-18(14-16)23-15-22-17/h1-2,5,9-11,14H,3-4,6-8,12-13,15H2
SMILES O=C(C=CC=CCCC1=CC=C2OCOC2=C1)N1CCCCC1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   313.17 Volume:   333.059
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Van der Waals volume.
Dense:   0.94 LogP:   3.709
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.238
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.31
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   38.77
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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:   0.617 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.445 Fsp3:   0.421
MCE-18:   34.222
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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:   0.379 Fluc inhibitor:   0.852
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.51
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.733
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.054 Promiscuous compounds:   0.036

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.581 MDCK Permeability:   -4.675
Pgp-inhibitor:   0.944 Pgp-substrate:   0.093
PAMPA:   0.008
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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):   0.002
20% Bioavailability (F20%):   0.021 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.205

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.861 MRP1:   0.163
Plasma Protein Binding (PPB):   98.049% Volume Distribution (VD):   0.392
Fu: 1.968%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.907
OATP1B3 inhibitor:   0.294 BCRP inhibitor:   0.01
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.919
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.085
CYP2C9-inhibitor:   0.974 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.046 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.989 CYP2C8-inhibitor:   0.445
HLM stability:   0.983
?
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):  4.934 Half-life (T1/2):  0.295

ADMET: Toxicity

hERG Blockers:  0.521 hERG Blockers (10um):  0.662
Human Hepatotoxicity (H-HT):  0.633 Drug-induced Liver Injury (DILI):  0.456
AMES Toxicity:  0.638 Rat Oral Acute Toxicity:  0.242
Maximum Recommended Daily Dose:  0.749 Skin Sensitization:  0.732
Carcinogencity:  0.526 Eye Corrosion:  0.016
Eye Irritation:  0.634 Respiratory Toxicity:  0.719
Drug-induced Neurotoxicity:  0.674 Ototoxicity:  0.379
Hematotoxicity:  0.404 Drug-induced Nephrotoxicity:  0.6
Genotoxicity:  0.278 RPMI-8226 Immunitoxicity:  0.117
A549 Cytotoxicity:  0.226 Hek293 Cytotoxicity:  0.63
BCF:   1.421
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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:   3.975
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.447
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.842
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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]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[16872768]
NPO26237 Piper longum Species Piperaceae Eukaryota fruits n.a. n.a. PMID[20839888]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[23102654]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[23434420]
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]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. Database[FooDB]
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]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
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]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26237 Piper longum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26237 Piper longum 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[TM-MC]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26237 Piper longum 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

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 NPC531724 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
0.9792 High Similarity NPC145446
0.9792 High Similarity NPC137172
0.86 High Similarity NPC252107
0.7857 Intermediate Similarity NPC95366
0.6964 Remote Similarity NPC248505
0.623 Remote Similarity NPC73883
0.623 Remote Similarity NPC251454
0.6129 Remote Similarity NPC220923
0.6129 Remote Similarity NPC196609
0.6102 Remote Similarity NPC205178
0.6102 Remote Similarity NPC227218
0.6066 Remote Similarity NPC103947
0.6066 Remote Similarity NPC45783
0.6034 Remote Similarity NPC255817
0.6034 Remote Similarity NPC136330
0.5968 Remote Similarity NPC328419
0.5965 Remote Similarity NPC605639
0.5862 Remote Similarity NPC94280
0.5789 Remote Similarity NPC608515
0.5614 Remote Similarity NPC167096
0.5614 Remote Similarity NPC605721
0.5469 Remote Similarity NPC99798
0.5439 Remote Similarity NPC217574
0.541 Remote Similarity NPC231572
0.5397 Remote Similarity NPC230698
0.5397 Remote Similarity NPC99078
0.5397 Remote Similarity NPC96406
0.5323 Remote Similarity NPC159150
0.5238 Remote Similarity NPC193673

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC531724 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
0.6034 Remote Similarity NPD2492 Phase 2

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