Natural Product: NPC301987

Natural Product IDNPC301987
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6-(8'z,11'z-Heptadecadienyl)-Salicylic Acid
IUPAC Name 2-[(8Z,11Z)-heptadeca-8,11-dienyl]-6-hydroxybenzoic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL465196
PubChem CID 10861650
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001248] Hydroxybenzoic acid derivatives
            • [CHEMONTID:0000487] Salicylic acid and derivatives
              • [CHEMONTID:0002514] Salicylic acids

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 OFFQPVDOVYHTBX-HZJYTTRNSA-N
Standard InCHI InChI=1S/C24H36O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-18-21-19-17-20-22(25)23(21)24(26)27/h6-7,9-10,17,19-20,25H,2-5,8,11-16,18H2,1H3,(H,26,27)/b7-6-,10-9-
SMILES CCCCC/C=CC/C=CCCCCCCCc1cccc(c1C(=O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.27 Volume:   425.656
?
Van der Waals volume.
Dense:   0.875 LogP:   8.315
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.025
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.546
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   15.0 Rigid Bonds:   9.0
TPSA:   57.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.256 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.518 Fsp3:   0.542
MCE-18:   7.0
?
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:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.644 Fluc inhibitor:   0.289
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.047
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.276
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.763 Promiscuous compounds:   0.245

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.065 MDCK Permeability:   -4.753
Pgp-inhibitor:   0.945 Pgp-substrate:   0.0
PAMPA:   0.001
?
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%):   0.159 30% Bioavailability (F30%):   0.775
50% Bioavailability (F50%):   0.906

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   1.0
Plasma Protein Binding (PPB):   98.183% Volume Distribution (VD):   -0.391
Fu: 0.615%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.05
OATP1B3 inhibitor:   0.491 BCRP inhibitor:   0.357
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.436
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.899 CYP2D6-substrate:   0.914
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.041 CYP2C8-inhibitor:   1.0
HLM stability:   0.58
?
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):  2.536 Half-life (T1/2):  0.856

ADMET: Toxicity

hERG Blockers:  0.307 hERG Blockers (10um):  0.407
Human Hepatotoxicity (H-HT):  0.184 Drug-induced Liver Injury (DILI):  0.002
AMES Toxicity:  0.125 Rat Oral Acute Toxicity:  0.048
Maximum Recommended Daily Dose:  0.022 Skin Sensitization:  1.0
Carcinogencity:  0.006 Eye Corrosion:  0.995
Eye Irritation:  0.998 Respiratory Toxicity:  0.935
Drug-induced Neurotoxicity:  0.004 Ototoxicity:  0.219
Hematotoxicity:  0.007 Drug-induced Nephrotoxicity:  0.68
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.042
A549 Cytotoxicity:  0.829 Hek293 Cytotoxicity:  0.161
BCF:   1.026
?
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:   4.545
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.97
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.624
?
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
NPO33539 Anacardium spondias Species Anacardiaceae Eukaryota leaves Agumatsa Wildlife Sanctuary-National Park, Ghana n.a. PMID[9834151]
NPO6707 Cosmopterix victor Species Cosmopterigidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8223 Gnaphalium polycaulon Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9081 Lecidea aglaeotera Species Lecideaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33539 Anacardium spondias Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9081 Lecidea aglaeotera Species Lecideaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8223 Gnaphalium polycaulon Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6707 Cosmopterix victor Species Cosmopterigidae 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
NPT863 Individual protein Trypsin Sus scrofa IC50 > 200000.0 nM PMID[9834151]
NPT4671 Protein complex Coagulation factor VII/tissue factor Homo sapiens IC50 = 33000.0 nM PMID[9834151]

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 NPC301987 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
0.9592 High Similarity NPC115188
0.9592 High Similarity NPC159760
0.9375 High Similarity NPC244994
0.9375 High Similarity NPC222876
0.9375 High Similarity NPC292665
0.9375 High Similarity NPC179092
0.92 High Similarity NPC26433
0.9167 High Similarity NPC238531
0.9167 High Similarity NPC178395
0.8958 High Similarity NPC483452
0.8824 High Similarity NPC184579
0.8824 High Similarity NPC233165
0.8125 Intermediate Similarity NPC483451
0.8125 Intermediate Similarity NPC227450
0.8125 Intermediate Similarity NPC272454
0.8125 Intermediate Similarity NPC35856
0.8125 Intermediate Similarity NPC609957
0.7963 Intermediate Similarity NPC167055
0.7719 Intermediate Similarity NPC240744
0.6852 Remote Similarity NPC605990
0.6667 Remote Similarity NPC244351
0.6667 Remote Similarity NPC483453
0.6607 Remote Similarity NPC17840
0.6607 Remote Similarity NPC247477
0.5323 Remote Similarity NPC489602
0.5143 Remote Similarity NPC71256

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC301987 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