Natural Product: NPC300455

Natural Product IDNPC300455
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2E,4E,6E)-N-Isopentyl-7-(2-Thienyl)-2,4,6-Heptatrienamide
IUPAC Name (2E,4E,6E)-N-(3-methylbutyl)-7-thiophen-2-ylhepta-2,4,6-trienamide
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2442635
PubChem CID 72696080
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000331] Fatty amides
          • [CHEMONTID:0001096] N-acyl amines

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 CDHCPJUXYQLWFD-IZMYCKBJSA-N
Standard InCHI InChI=1S/C16H21NOS/c1-14(2)11-12-17-16(18)10-6-4-3-5-8-15-9-7-13-19-15/h3-10,13-14H,11-12H2,1-2H3,(H,17,18)/b4-3+,8-5+,10-6+
SMILES CC(CCN=C(/C=C/C=C/C=C/c1cccs1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   275.13 Volume:   299.213
?
Van der Waals volume.
Dense:   0.92 LogP:   3.9
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.236
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.448
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   9.0
TPSA:   32.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.429 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.303 Fsp3:   0.312
MCE-18:   6.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.987 Fluc inhibitor:   0.986
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.137
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.874
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.294 Promiscuous compounds:   0.088

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.719 MDCK Permeability:   -4.526
Pgp-inhibitor:   0.292 Pgp-substrate:   0.156
PAMPA:   0.303
?
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):   0.169
20% Bioavailability (F20%):   0.912 30% Bioavailability (F30%):   0.985
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.028
Plasma Protein Binding (PPB):   97.55% Volume Distribution (VD):   0.079
Fu: 2.136%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.036
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.156 CYP1A2-substrate:   0.967
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.675
CYP2C9-inhibitor:   0.596 CYP2C9-substrate:   0.348
CYP2D6-inhibitor:   0.952 CYP2D6-substrate:   0.019
CYP3A4-inhibitor:   0.018 CYP3A4-substrate:   0.988
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.86
?
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):  9.437 Half-life (T1/2):  0.455

ADMET: Toxicity

hERG Blockers:  0.122 hERG Blockers (10um):  0.339
Human Hepatotoxicity (H-HT):  0.937 Drug-induced Liver Injury (DILI):  0.905
AMES Toxicity:  0.875 Rat Oral Acute Toxicity:  0.562
Maximum Recommended Daily Dose:  0.269 Skin Sensitization:  0.987
Carcinogencity:  0.862 Eye Corrosion:  0.088
Eye Irritation:  0.854 Respiratory Toxicity:  0.944
Drug-induced Neurotoxicity:  0.235 Ototoxicity:  0.487
Hematotoxicity:  0.348 Drug-induced Nephrotoxicity:  0.658
Genotoxicity:  0.751 RPMI-8226 Immunitoxicity:  0.019
A549 Cytotoxicity:  0.026 Hek293 Cytotoxicity:  0.144
BCF:   1.357
?
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:   3.851
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.948
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.626
?
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
NPO14864 Clerodendrum cyrtophyllum Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[11473423]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[11575948]
NPO12347 Pseudomonas syringae Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[14714872]
NPO15548 Sinularia leptoclados Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[16724859]
NPO13549 Otanthus maritimus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[39715713]
NPO3974 Ferula gummosa Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20070 Crinum stuhlmannii Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4699 Dracaena ombet Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11683 Crotalaria mitchellii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6367 Cortinarius viola Species Cortinariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14864 Clerodendrum cyrtophyllum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26712 Cladrastis kentukea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15166 Cephalotaxus hainanensis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4503 Bryonopsis laciniosa n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO14191 Berkheya rhapontica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11151 Arnebia decumbens Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19872 Achillea magnifica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14989 Acanthothamnus aphyllus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4518.1 Saccharothrix mutabilis subsp. capreolus Subspecies Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO9734 Vincetoxicum hirundinaria Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22084 Stypandra imbricata Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12121 Streptomyces naraensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO15548 Sinularia leptoclados Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1027 Scrophularia leucoclada Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13320 Glycosmis puberula Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5469 Pseudoxandra sclerocarpa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12993 Polypodium vulgare Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15066 Iridaea membranacea Species Gigartinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13549 Otanthus maritimus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11505 Nigella aristata Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7042 Myrica arborea Species Myricaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12539 Lissoclinum japonicum Species Didemnidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8392 Iryanthera polyneura Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9338 Polygala aureocauda Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12993 Polypodium vulgare Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15166 Cephalotaxus hainanensis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9734 Vincetoxicum hirundinaria Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12993 Polypodium vulgare Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7042 Myrica arborea Species Myricaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8392 Iryanthera polyneura Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15166 Cephalotaxus hainanensis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12993 Polypodium vulgare Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15166 Cephalotaxus hainanensis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22084 Stypandra imbricata Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1027 Scrophularia leucoclada Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15066 Iridaea membranacea Species Gigartinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11505 Nigella aristata Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14989 Acanthothamnus aphyllus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12121 Streptomyces naraensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO15166 Cephalotaxus hainanensis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12993 Polypodium vulgare Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12347 Pseudomonas syringae Species Pseudomonadaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO11683 Crotalaria mitchellii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14864 Clerodendrum cyrtophyllum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9734 Vincetoxicum hirundinaria Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19872 Achillea magnifica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8392 Iryanthera polyneura Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4699 Dracaena ombet Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15548 Sinularia leptoclados Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11151 Arnebia decumbens Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4503 Bryonopsis laciniosa n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO20070 Crinum stuhlmannii Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12539 Lissoclinum japonicum Species Didemnidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5469 Pseudoxandra sclerocarpa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7042 Myrica arborea Species Myricaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4518.1 Saccharothrix mutabilis subsp. capreolus Subspecies Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO6367 Cortinarius viola Species Cortinariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13549 Otanthus maritimus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26712 Cladrastis kentukea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3974 Ferula gummosa Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13320 Glycosmis puberula Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14191 Berkheya rhapontica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9338 Polygala aureocauda Species Polygalaceae 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
NPT1167 Individual protein Delta opioid receptor Mus musculus Ki = 26500.0 nM PMID[24095014]
NPT1168 Individual protein Mu opioid receptor Mus musculus Ki = 8100.0 nM PMID[24095014]
NPT1169 Individual protein Cannabinoid CB2 receptor Mus musculus Ki = 5000.0 nM PMID[24095014]
NPT1170 Individual protein Cannabinoid CB1 receptor Mus musculus Ki = 2200.0 nM PMID[24095014]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Ratio Ki = 3.27 n.a. PMID[24095014]
NPT2 Others Unspecified n.a. Ratio Ki = 0.44 n.a. PMID[24095014]

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 NPC300455 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
0.7755 Intermediate Similarity NPC166487
0.6885 Remote Similarity NPC190955

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC300455 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
NPD

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