Natural Product: NPC604140

Natural Product IDNPC604140
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DZIILFGADWDKMF-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL182310
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 DZIILFGADWDKMF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h1H,3-17H2,(H,19,20)
SMILES C#CCCCCCCCCCCCCCCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   280.24 Volume:   329.555
?
Van der Waals volume.
Dense:   0.85 LogP:   6.038
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.115
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.254
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   15.0 Rigid Bonds:   2.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.315 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.101 Fsp3:   0.833
MCE-18:   0.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.074 Fluc inhibitor:   0.034
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.99 Promiscuous compounds:   0.178

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.101 MDCK Permeability:   -4.787
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   0.339
?
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):   0.529
20% Bioavailability (F20%):   0.147 30% Bioavailability (F30%):   0.383
50% Bioavailability (F50%):   0.262

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.045 MRP1:   0.015
Plasma Protein Binding (PPB):   98.318% Volume Distribution (VD):   0.541
Fu: 1.024%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.837
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.412
BSEP inhibitor:   0.061

ADMET: Metabolism

CYP1A2-inhibitor:   0.034 CYP1A2-substrate:   0.112
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.991
CYP2C9-inhibitor:   0.994 CYP2C9-substrate:   0.583
CYP2D6-inhibitor:   0.03 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.318 CYP3A4-substrate:   0.15
CYP2B6-substrate:   0.943 CYP2C8-inhibitor:   0.961
HLM stability:   0.01
?
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):  3.704 Half-life (T1/2):  1.022

ADMET: Toxicity

hERG Blockers:  0.014 hERG Blockers (10um):  0.164
Human Hepatotoxicity (H-HT):  0.655 Drug-induced Liver Injury (DILI):  0.008
AMES Toxicity:  0.1 Rat Oral Acute Toxicity:  0.196
Maximum Recommended Daily Dose:  0.248 Skin Sensitization:  0.996
Carcinogencity:  0.368 Eye Corrosion:  0.992
Eye Irritation:  0.997 Respiratory Toxicity:  0.996
Drug-induced Neurotoxicity:  0.018 Ototoxicity:  0.256
Hematotoxicity:  0.21 Drug-induced Nephrotoxicity:  0.851
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.043
A549 Cytotoxicity:  0.001 Hek293 Cytotoxicity:  0.017
BCF:   0.922
?
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:   3.812
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.554
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   1.908
?
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]
NPO30686 Citrus hystrix Species Rutaceae Eukaryota n.a. exocarp n.a. PMID[20964319]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[23102654]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota n.a. leaf n.a. PMID[24024688]
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]
NPO30686 Citrus hystrix Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[38067483]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[38067483]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota n.a. n.a. n.a. PMID[38194794]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota n.a. n.a. n.a. PMID[38195615]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[38474459]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota n.a. n.a. n.a. PMID[38681233]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota n.a. n.a. n.a. PMID[38731845]
NPO45819 Fortunella Japonica Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[38981879]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota n.a. n.a. n.a. PMID[39553766]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota n.a. n.a. n.a. PMID[39723058]
NPO4254 Wedelia glauca Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[6533263]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota n.a. n.a. n.a. PMID[7798960]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30686 Citrus hystrix Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4254 Wedelia glauca Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. Database[FooDB]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota n.a. n.a. Database[FooDB]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO28928 Piper nigrum Species Piperaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO11021 Moringa oleifera Species Moringaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO28928 Piper nigrum Species Piperaceae Eukaryota n.a. n.a. Database[FooDB]
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]
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]
NPO4254 Wedelia glauca Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11021 Moringa oleifera Species Moringaceae 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
NPO11021 Moringa oleifera n.a. n.a. 0.99 n.a. n.a. % PMID[38195615]
NPO28928 Piper nigrum CO2 extract n.a. 0.025 n.a. n.a. % PMID[38067483]
NPO30686 Citrus hystrix CO2 extract n.a. 0.12 n.a. n.a. % PMID[38067483]
NPO45819 Fortunella Japonica n.a. Fruits 0.309 n.a. n.a. % PMID[38981879]

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
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT149 Individual protein Endoplasmic reticulum-associated amyloid beta-peptide-binding protein Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens AC50 = 19952.62 nM PubChem BioAssay data set
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens AC50 = 25118.86 nM PubChem BioAssay data set
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens Potency = 19952.6 nM PubChem BioAssay data set
NPT150 Individual protein Anthrax lethal factor Bacillus anthracis Potency = 31622.8 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens AC50 = 12589.25 nM PubChem BioAssay data set
NPT208 Individual protein Cytochrome P450 1A2 Homo sapiens AC50 = 6309.57 nM PubChem BioAssay data set
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 7079.5 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 28183.8 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 100.0 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 3548.1 nM PubChem BioAssay data set
NPT24846 Single protein Cytochrome P450 4F2 Homo sapiens IC50 < 5000.0 nM PMID[22932312]
NPT443 Individual protein Histone acetyltransferase GCN5 Homo sapiens Potency n.a. 11220.2 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. IC50 > 5000.0 nM PMID[15454216]
NPT28438 Unchecked Unchecked n.a. Potency = 25118.9 nM PubChem BioAssay data set

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 NPC604140 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
0.8095 Intermediate Similarity NPC214610
0.8095 Intermediate Similarity NPC118968
0.8095 Intermediate Similarity NPC183424
0.8095 Intermediate Similarity NPC294085
0.7619 Intermediate Similarity NPC268826
0.7407 Intermediate Similarity NPC8219
0.7083 Intermediate Similarity NPC171736
0.7083 Intermediate Similarity NPC301585
0.7083 Intermediate Similarity NPC261080
0.7083 Intermediate Similarity NPC132565
0.7083 Intermediate Similarity NPC209970
0.7083 Intermediate Similarity NPC216630
0.7083 Intermediate Similarity NPC201844
0.7083 Intermediate Similarity NPC301696
0.7083 Intermediate Similarity NPC196924
0.7083 Intermediate Similarity NPC307783
0.7083 Intermediate Similarity NPC154186
0.7083 Intermediate Similarity NPC149184
0.7083 Intermediate Similarity NPC279026
0.7083 Intermediate Similarity NPC113928
0.7083 Intermediate Similarity NPC14227
0.6818 Remote Similarity NPC134782
0.6786 Remote Similarity NPC129972
0.6786 Remote Similarity NPC301528
0.6786 Remote Similarity NPC71317
0.6786 Remote Similarity NPC163746
0.6786 Remote Similarity NPC103286
0.6667 Remote Similarity NPC155263
0.6296 Remote Similarity NPC180534
0.6296 Remote Similarity NPC55023
0.6296 Remote Similarity NPC21844
0.6296 Remote Similarity NPC611531
0.625 Remote Similarity NPC175342
0.6071 Remote Similarity NPC50457
0.6071 Remote Similarity NPC604910
0.6061 Remote Similarity NPC18357
0.5909 Remote Similarity NPC18224
0.5862 Remote Similarity NPC34416
0.5862 Remote Similarity NPC314679
0.5862 Remote Similarity NPC281245
0.5714 Remote Similarity NPC304162
0.5667 Remote Similarity NPC424
0.5667 Remote Similarity NPC36061
0.5667 Remote Similarity NPC69510
0.5667 Remote Similarity NPC77272
0.5667 Remote Similarity NPC290563
0.5667 Remote Similarity NPC139029
0.5667 Remote Similarity NPC281972
0.5667 Remote Similarity NPC261831
0.5667 Remote Similarity NPC87564
0.5652 Remote Similarity NPC174368
0.5484 Remote Similarity NPC18712
0.5484 Remote Similarity NPC73245
0.5484 Remote Similarity NPC74845
0.5484 Remote Similarity NPC95145
0.5484 Remote Similarity NPC325642
0.5484 Remote Similarity NPC65174
0.5405 Remote Similarity NPC100096
0.5405 Remote Similarity NPC179764
0.5357 Remote Similarity NPC323974
0.5357 Remote Similarity NPC317203
0.5312 Remote Similarity NPC158179
0.5312 Remote Similarity NPC87394
0.5312 Remote Similarity NPC324004
0.5312 Remote Similarity NPC328497
0.5312 Remote Similarity NPC602547
0.5263 Remote Similarity NPC187777
0.5172 Remote Similarity NPC602752
0.5161 Remote Similarity NPC92114
0.5152 Remote Similarity NPC52955
0.5152 Remote Similarity NPC88966
0.5152 Remote Similarity NPC25417
0.5152 Remote Similarity NPC1813
0.5152 Remote Similarity NPC154245
0.5152 Remote Similarity NPC85813
0.5152 Remote Similarity NPC223697
0.5152 Remote Similarity NPC174560
0.5152 Remote Similarity NPC125312
0.5152 Remote Similarity NPC6095
0.5128 Remote Similarity NPC54766

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC604140 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
0.8095 Intermediate Similarity NPD9655 Phase 4
0.7083 Intermediate Similarity NPD2270 Pre-clinical
0.7083 Intermediate Similarity NPD633 Phase 3
0.7083 Intermediate Similarity NPD9448 Phase 2
0.6296 Remote Similarity NPD622 Pre-clinical
0.5667 Remote Similarity NPD3195 Phase 2
0.5667 Remote Similarity NPD3196 Approved
0.5357 Remote Similarity NPD9019 Phase 4
0.5312 Remote Similarity NPD3199 Clinical (unspecified phase)
0.5152 Remote Similarity NPD3172 Approved
0.5152 Remote Similarity NPD4266 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