Natural Product: NPC566428

Natural Product IDNPC566428
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Decenedioic acid
IUPAC Name dec-2-enedioic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
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 XUNMWLWTZWWEIE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C10H16O4/c11-9(12)7-5-3-1-2-4-6-8-10(13)14/h5,7H,1-4,6,8H2,(H,11,12)(H,13,14)
SMILES O=C(O)C=CCCCCCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   200.1 Volume:   208.768
?
Van der Waals volume.
Dense:   0.958 LogP:   2.0
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.909
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.959
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   3.0
TPSA:   74.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.464 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.058 Fsp3:   0.6
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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.004 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.009
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.008
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.996 Promiscuous compounds:   0.615

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.071 MDCK Permeability:   -4.753
Pgp-inhibitor:   0.0 Pgp-substrate:   0.02
PAMPA:   1.0
?
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):   0.726
20% Bioavailability (F20%):   0.192 30% Bioavailability (F30%):   0.22
50% Bioavailability (F50%):   0.084

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.992
Plasma Protein Binding (PPB):   79.372% Volume Distribution (VD):   -0.422
Fu: 16.998%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.144
OATP1B3 inhibitor:   0.826 BCRP inhibitor:   0.001
BSEP inhibitor:   0.011

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.037
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.123 CYP2C8-inhibitor:   0.636
HLM stability:   0.002
?
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):  1.982 Half-life (T1/2):  1.203

ADMET: Toxicity

hERG Blockers:  0.012 hERG Blockers (10um):  0.026
Human Hepatotoxicity (H-HT):  0.261 Drug-induced Liver Injury (DILI):  0.313
AMES Toxicity:  0.123 Rat Oral Acute Toxicity:  0.197
Maximum Recommended Daily Dose:  0.062 Skin Sensitization:  0.859
Carcinogencity:  0.126 Eye Corrosion:  0.985
Eye Irritation:  0.997 Respiratory Toxicity:  0.537
Drug-induced Neurotoxicity:  0.056 Ototoxicity:  0.495
Hematotoxicity:  0.247 Drug-induced Nephrotoxicity:  0.555
Genotoxicity:  0.021 RPMI-8226 Immunitoxicity:  0.017
A549 Cytotoxicity:  0.002 Hek293 Cytotoxicity:  0.005
BCF:   0.255
?
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:   2.871
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.18
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.1
?
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
NPO20756 Aspergillus unilateralis Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[15602607]
NPO20756 Aspergillus unilateralis Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20756 Aspergillus unilateralis Species Aspergillaceae 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

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 NPC566428 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 NPC34416
0.7143 Intermediate Similarity NPC180534
0.7143 Intermediate Similarity NPC611531
0.68 Remote Similarity NPC214610
0.68 Remote Similarity NPC118968
0.68 Remote Similarity NPC183424
0.68 Remote Similarity NPC294085
0.6667 Remote Similarity NPC281245
0.6452 Remote Similarity NPC424
0.6452 Remote Similarity NPC36061
0.6452 Remote Similarity NPC69510
0.6452 Remote Similarity NPC77272
0.6452 Remote Similarity NPC290563
0.6452 Remote Similarity NPC139029
0.6452 Remote Similarity NPC281972
0.6452 Remote Similarity NPC261831
0.6452 Remote Similarity NPC87564
0.6429 Remote Similarity NPC202716
0.64 Remote Similarity NPC268826
0.625 Remote Similarity NPC95145
0.625 Remote Similarity NPC325642
0.625 Remote Similarity NPC65174
0.6071 Remote Similarity NPC171736
0.6071 Remote Similarity NPC301585
0.6071 Remote Similarity NPC261080
0.6071 Remote Similarity NPC132565
0.6071 Remote Similarity NPC209970
0.6071 Remote Similarity NPC216630
0.6071 Remote Similarity NPC201844
0.6071 Remote Similarity NPC301696
0.6071 Remote Similarity NPC196924
0.6071 Remote Similarity NPC307783
0.6071 Remote Similarity NPC154186
0.6071 Remote Similarity NPC149184
0.6071 Remote Similarity NPC279026
0.6071 Remote Similarity NPC113928
0.6071 Remote Similarity NPC14227
0.5938 Remote Similarity NPC92114
0.5882 Remote Similarity NPC52955
0.5882 Remote Similarity NPC88966
0.5882 Remote Similarity NPC25417
0.5882 Remote Similarity NPC1813
0.5882 Remote Similarity NPC154245
0.5882 Remote Similarity NPC85813
0.5882 Remote Similarity NPC223697
0.5882 Remote Similarity NPC6095
0.5862 Remote Similarity NPC604140
0.5769 Remote Similarity NPC134782
0.5714 Remote Similarity NPC155263
0.5714 Remote Similarity NPC221250
0.5588 Remote Similarity NPC321062
0.5588 Remote Similarity NPC70387
0.5484 Remote Similarity NPC55023
0.5484 Remote Similarity NPC21844
0.5429 Remote Similarity NPC174560
0.5429 Remote Similarity NPC125312
0.5357 Remote Similarity NPC175342
0.5312 Remote Similarity NPC50457
0.5312 Remote Similarity NPC604910
0.5263 Remote Similarity NPC225929
0.5263 Remote Similarity NPC606120
0.5152 Remote Similarity NPC314679
0.5143 Remote Similarity NPC5413

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC566428 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 NPD622 Pre-clinical
0.68 Remote Similarity NPD9655 Phase 4
0.6452 Remote Similarity NPD3195 Phase 2
0.6452 Remote Similarity NPD3196 Approved
0.6071 Remote Similarity NPD2270 Pre-clinical
0.6071 Remote Similarity NPD633 Phase 3
0.6071 Remote Similarity NPD9448 Phase 2
0.5882 Remote Similarity NPD3172 Approved
0.5882 Remote Similarity NPD4266 Phase 2
0.5263 Remote Similarity NPD3194 Phase 4
0.5143 Remote Similarity NPD3173 Phase 4

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