Natural Product: NPC137172

Natural Product IDNPC137172
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-(Benzo[D][1,3]Dioxol-5-Yl)-1-(Pyrrolidin-1-Yl)Hepta-2,4-Dien-1-One
IUPAC Name (2E,4E)-7-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-ylhepta-2,4-dien-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3338703
PubChem CID 10447462
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 IODPUHWFWZSHCM-AIWOWGKTSA-N
Standard InCHI InChI=1S/C18H21NO3/c20-18(19-11-5-6-12-19)8-4-2-1-3-7-15-9-10-16-17(13-15)22-14-21-16/h1-2,4,8-10,13H,3,5-7,11-12,14H2/b2-1+,8-4+
SMILES O=C(N1CCCC1)/C=C/C=C/CCc1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   299.15 Volume:   315.764
?
Van der Waals volume.
Dense:   0.947 LogP:   2.94
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.897
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.87
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 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:   0.619 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.451 Fsp3:   0.389
MCE-18:   33.6
?
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:   0.341 Fluc inhibitor:   0.865
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.556
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.708
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.031 Promiscuous compounds:   0.027

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.618 MDCK Permeability:   -4.634
Pgp-inhibitor:   0.964 Pgp-substrate:   0.041
PAMPA:   0.04
?
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%):   0.036 30% Bioavailability (F30%):   0.014
50% Bioavailability (F50%):   0.8

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.02
Plasma Protein Binding (PPB):   98.137% Volume Distribution (VD):   -0.143
Fu: 1.708%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.935
OATP1B3 inhibitor:   0.732 BCRP inhibitor:   0.01
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.99
CYP2C19-inhibitor:   0.923 CYP2C19-substrate:   0.997
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.054 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.111 CYP2C8-inhibitor:   0.997
HLM stability:   0.872
?
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):  5.257 Half-life (T1/2):  0.531

ADMET: Toxicity

hERG Blockers:  0.577 hERG Blockers (10um):  0.594
Human Hepatotoxicity (H-HT):  0.777 Drug-induced Liver Injury (DILI):  0.777
AMES Toxicity:  0.834 Rat Oral Acute Toxicity:  0.278
Maximum Recommended Daily Dose:  0.813 Skin Sensitization:  0.686
Carcinogencity:  0.609 Eye Corrosion:  0.001
Eye Irritation:  0.365 Respiratory Toxicity:  0.836
Drug-induced Neurotoxicity:  0.751 Ototoxicity:  0.509
Hematotoxicity:  0.54 Drug-induced Nephrotoxicity:  0.688
Genotoxicity:  0.861 RPMI-8226 Immunitoxicity:  0.137
A549 Cytotoxicity:  0.127 Hek293 Cytotoxicity:  0.645
BCF:   1.434
?
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:   4.077
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.494
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.965
?
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
NPT81 Cell line A549 Homo sapiens IC50 = 24650.0 nM PMID[25241925]
NPT83 Cell line MCF7 Homo sapiens IC50 > 40000.0 nM PMID[25241925]
NPT133 Cell line ZR-75-1 Homo sapiens IC50 > 40000.0 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 > 33000.0 nM PMID[25241925]
NPT91 Cell line KB Homo sapiens IC50 > 33000.0 nM PMID[25241925]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 31000.0 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 NPC137172 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
1.0 High Similarity NPC145446
0.84 Intermediate Similarity NPC252107
0.7679 Intermediate Similarity NPC95366
0.7091 Intermediate Similarity NPC248505
0.6167 Remote Similarity NPC103947
0.6167 Remote Similarity NPC45783
0.6066 Remote Similarity NPC328419
0.6066 Remote Similarity NPC73883
0.6066 Remote Similarity NPC251454
0.5968 Remote Similarity NPC220923
0.5968 Remote Similarity NPC196609
0.5965 Remote Similarity NPC94280
0.5932 Remote Similarity NPC205178
0.5932 Remote Similarity NPC227218
0.5893 Remote Similarity NPC608515
0.5862 Remote Similarity NPC255817
0.5862 Remote Similarity NPC136330
0.5789 Remote Similarity NPC605639
0.5556 Remote Similarity NPC99798
0.5536 Remote Similarity NPC217574
0.5439 Remote Similarity NPC167096
0.5439 Remote Similarity NPC605721
0.541 Remote Similarity NPC159150
0.5323 Remote Similarity NPC193673
0.5246 Remote Similarity NPC231572
0.5238 Remote Similarity NPC230698
0.5238 Remote Similarity NPC99078
0.5238 Remote Similarity NPC96406
0.5079 Remote Similarity NPC157740

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC137172 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
0.5862 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