Natural Product: NPC328419

Natural Product IDNPC328419
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 11-(Benzo[D][1,3]Dioxol-5-Yl)-1-(Pyrrolidin-1-Yl)Undeca-2,4,10-Trien-1-One
IUPAC Name (2E,4E,10E)-11-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-ylundeca-2,4,10-trien-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1669199
PubChem CID 50994145
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 NYSPLUVUHIKYHV-AWHUYLLYSA-N
Standard InCHI InChI=1S/C22H27NO3/c24-22(23-15-9-10-16-23)12-8-6-4-2-1-3-5-7-11-19-13-14-20-21(17-19)26-18-25-20/h4,6-8,11-14,17H,1-3,5,9-10,15-16,18H2/b6-4+,11-7+,12-8+
SMILES C1CCN(C1)C(=O)C=CC=CCCCCC=CC2=CC3=C(C=C2)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   353.2 Volume:   382.311
?
Van der Waals volume.
Dense:   0.924 LogP:   4.666
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.526
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.997
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   19.0
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:   0.385 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.623 Fsp3:   0.409
MCE-18:   32.516
?
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:   0.853 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.629
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.912
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.055 Promiscuous compounds:   0.044

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.653 MDCK Permeability:   -4.68
Pgp-inhibitor:   0.763 Pgp-substrate:   0.007
PAMPA:   0.014
?
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%):   0.075 30% Bioavailability (F30%):   0.007
50% Bioavailability (F50%):   0.513

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.936 MRP1:   0.395
Plasma Protein Binding (PPB):   97.036% Volume Distribution (VD):   0.232
Fu: 2.564%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.85
OATP1B3 inhibitor:   0.937 BCRP inhibitor:   0.08
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.975 CYP1A2-substrate:   0.419
CYP2C19-inhibitor:   0.827 CYP2C19-substrate:   0.851
CYP2C9-inhibitor:   0.995 CYP2C9-substrate:   0.944
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.468 CYP2C8-inhibitor:   1.0
HLM stability:   0.763
?
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):  4.33 Half-life (T1/2):  0.427

ADMET: Toxicity

hERG Blockers:  0.662 hERG Blockers (10um):  0.712
Human Hepatotoxicity (H-HT):  0.544 Drug-induced Liver Injury (DILI):  0.036
AMES Toxicity:  0.723 Rat Oral Acute Toxicity:  0.197
Maximum Recommended Daily Dose:  0.547 Skin Sensitization:  0.999
Carcinogencity:  0.244 Eye Corrosion:  0.1
Eye Irritation:  0.738 Respiratory Toxicity:  0.481
Drug-induced Neurotoxicity:  0.337 Ototoxicity:  0.367
Hematotoxicity:  0.127 Drug-induced Nephrotoxicity:  0.651
Genotoxicity:  0.006 RPMI-8226 Immunitoxicity:  0.141
A549 Cytotoxicity:  0.638 Hek293 Cytotoxicity:  0.759
BCF:   1.682
?
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:   4.413
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.919
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.257
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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
NPO30128 Piper boehmeriaefolium Species Piperaceae Eukaryota whole plant Luxi County, Yunnan Province, China 2008-OCT PMID[21158422]
NPO30128 Piper boehmeriaefolium Species Piperaceae Eukaryota n.a. whole plant n.a. PMID[21158422]
NPO30128 Piper boehmeriaefolium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30128 Piper boehmeriaefolium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]

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
NPT165 Cell line HeLa Homo sapiens IC50 = 11.61 ug.mL-1 PMID[21158422]
NPT81 Cell line A549 Homo sapiens IC50 = 18300.0 nM PMID[25241925]
NPT83 Cell line MCF7 Homo sapiens IC50 = 30130.0 nM PMID[25241925]
NPT133 Cell line ZR-75-1 Homo sapiens IC50 = 40600.0 nM PMID[25241925]
NPT134 Cell line SK-BR-3 Homo sapiens IC50 > 40000.0 nM PMID[25241925]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 40000.0 nM PMID[25241925]
NPT90 Cell line DU-145 Homo sapiens IC50 = 20430.0 nM PMID[25241925]
NPT91 Cell line KB Homo sapiens IC50 = 21200.0 nM PMID[25241925]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 18930.0 nM PMID[25241925]
NPT2 Others Unspecified n.a. Ratio IC50 = 1.1 n.a. PMID[25241925]

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 NPC328419 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
0.9808 High Similarity NPC220923
0.9808 High Similarity NPC196609
0.9057 High Similarity NPC103947
0.9057 High Similarity NPC45783
0.8889 High Similarity NPC73883
0.8889 High Similarity NPC251454
0.8679 High Similarity NPC193673
0.8519 High Similarity NPC230698
0.8519 High Similarity NPC99078
0.8519 High Similarity NPC96406
0.7818 Intermediate Similarity NPC159150
0.7273 Intermediate Similarity NPC94280
0.7241 Intermediate Similarity NPC318862
0.7193 Intermediate Similarity NPC205178
0.7193 Intermediate Similarity NPC227218
0.7143 Intermediate Similarity NPC255817
0.7143 Intermediate Similarity NPC136330
0.6897 Remote Similarity NPC194359
0.6897 Remote Similarity NPC28641
0.6897 Remote Similarity NPC180647
0.6897 Remote Similarity NPC225745
0.6852 Remote Similarity NPC217574
0.6727 Remote Similarity NPC167096
0.6727 Remote Similarity NPC605721
0.6613 Remote Similarity NPC95366
0.6066 Remote Similarity NPC145446
0.6066 Remote Similarity NPC137172
0.6061 Remote Similarity NPC71105
0.6034 Remote Similarity NPC470707
0.597 Remote Similarity NPC41331
0.597 Remote Similarity NPC291449
0.5645 Remote Similarity NPC69670
0.5606 Remote Similarity NPC152186
0.5556 Remote Similarity NPC248505
0.5522 Remote Similarity NPC156944
0.5455 Remote Similarity NPC114845
0.5441 Remote Similarity NPC170583
0.5238 Remote Similarity NPC252107
0.5217 Remote Similarity NPC270811
0.5217 Remote Similarity NPC471073
0.5161 Remote Similarity NPC469808
0.5147 Remote Similarity NPC191302

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC328419 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
0.7143 Intermediate 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