Natural Product: NPC33168

Natural Product IDNPC33168
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Pyramidatine
IUPAC Name N-[4-[[(E)-3-phenylprop-2-enoyl]amino]butyl]benzamide
Synonyms Pyramidatine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL483414
PubChem CID 1755965
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0002810] Cinnamic acid amides

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 XYVZRTYPQHUZGY-BUHFOSPRSA-N
Standard InCHI InChI=1S/C20H22N2O2/c23-19(14-13-17-9-3-1-4-10-17)21-15-7-8-16-22-20(24)18-11-5-2-6-12-18/h1-6,9-14H,7-8,15-16H2,(H,21,23)(H,22,24)/b14-13+
SMILES c1ccc(cc1)/C=C/C(=NCCCCN=C(c1ccccc1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   322.17 Volume:   353.209
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Van der Waals volume.
Dense:   0.912 LogP:   3.28
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.371
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.421
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   15.0
TPSA:   65.18
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.428 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.537 Fsp3:   0.2
MCE-18:   10.0
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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:   0.955 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.092
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.927
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.031 Promiscuous compounds:   0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.58 MDCK Permeability:   -4.758
Pgp-inhibitor:   0.013 Pgp-substrate:   0.218
PAMPA:   0.971
?
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):   0.108
20% Bioavailability (F20%):   0.9 30% Bioavailability (F30%):   0.972
50% Bioavailability (F50%):   0.953

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.028 MRP1:   0.297
Plasma Protein Binding (PPB):   98.078% Volume Distribution (VD):   -0.443
Fu: 1.067%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.946
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.002
BSEP inhibitor:   0.281

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.841
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.174
CYP2C9-inhibitor:   0.885 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.996 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   0.133
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.011
?
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):  5.363 Half-life (T1/2):  0.484

ADMET: Toxicity

hERG Blockers:  0.261 hERG Blockers (10um):  0.202
Human Hepatotoxicity (H-HT):  0.962 Drug-induced Liver Injury (DILI):  0.626
AMES Toxicity:  0.844 Rat Oral Acute Toxicity:  0.521
Maximum Recommended Daily Dose:  0.394 Skin Sensitization:  0.998
Carcinogencity:  0.614 Eye Corrosion:  0.0
Eye Irritation:  0.19 Respiratory Toxicity:  0.612
Drug-induced Neurotoxicity:  0.508 Ototoxicity:  0.573
Hematotoxicity:  0.46 Drug-induced Nephrotoxicity:  0.817
Genotoxicity:  0.607 RPMI-8226 Immunitoxicity:  0.004
A549 Cytotoxicity:  0.032 Hek293 Cytotoxicity:  0.271
BCF:   0.589
?
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:   3.274
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.378
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.823
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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
NPO32616 aglaia sp. Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[10775404]
NPO26039 Nocardiopsis lucentensis Species Nocardiopsaceae Bacteria n.a. n.a. n.a. PMID[17630797]
NPO32616 aglaia sp. Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[8496701]
NPO32616 aglaia sp. Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[9868148]
NPO32616 aglaia sp. Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24598 Steiractinia mollis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25959 Silphium asteriscus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10961 Lejeunea flava Species Lejeuneaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3108 Artemisia nova Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26039 Nocardiopsis lucentensis Species Nocardiopsaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO26071 Hypoxylon haematostroma Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3108 Artemisia nova Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10961 Lejeunea flava Species Lejeuneaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24598 Steiractinia mollis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26039 Nocardiopsis lucentensis Species Nocardiopsaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO26071 Hypoxylon haematostroma Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25959 Silphium asteriscus Species Asteraceae 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
NPT453 Cell line HT-1080 Homo sapiens ED50 > 20.0 ug ml-1 PMID[8496701]
NPT147 Cell line SK-MEL-2 Homo sapiens ED50 > 20.0 ug ml-1 PMID[8496701]
NPT91 Cell line KB Homo sapiens ED50 > 20.0 ug ml-1 PMID[8496701]
NPT762 Cell line A-431 Homo sapiens ED50 > 20.0 ug ml-1 PMID[8496701]
NPT858 Cell line LNCaP Homo sapiens ED50 > 20.0 ug ml-1 PMID[8496701]
NPT133 Cell line ZR-75-1 Homo sapiens ED50 > 20.0 ug ml-1 PMID[8496701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 > 20.0 ug ml-1 PMID[8496701]

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 NPC33168 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
0.5306 Remote Similarity NPC203076
0.5167 Remote Similarity NPC471447

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC33168 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
0.5079 Remote Similarity NPD5103 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