Natural Product: NPC40663

Natural Product IDNPC40663
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Domoic Acid
IUPAC Name (2S,3S,4S)-4-[(2Z,4E,6R)-6-carboxyhepta-2,4-dien-2-yl]-3-(carboxymethyl)pyrrolidine-2-carboxylic acid
Synonyms Domoic Acid
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1232313
PubChem CID 5282253
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0000013] Amino acids, peptides, and analogues
          • [CHEMONTID:0000347] Amino acids and derivatives
            • [CHEMONTID:0001801] Kainoids

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 VZFRNCSOCOPNDB-AOKDLOFSSA-N
Standard InCHI InChI=1S/C15H21NO6/c1-8(4-3-5-9(2)14(19)20)11-7-16-13(15(21)22)10(11)6-12(17)18/h3-5,9-11,13,16H,6-7H2,1-2H3,(H,17,18)(H,19,20)(H,21,22)/b5-3+,8-4-/t9-,10+,11-,13+/m1/s1
SMILES C/C(=C/C=C/[C@@H](C)C(=O)O)/[C@H]1CN[C@@H]([C@H]1CC(=O)O)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   311.14 Volume:   309.996
?
Van der Waals volume.
Dense:   1.004 LogP:   -0.153
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.677
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.892
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   10.0
TPSA:   123.93
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   1.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.516 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.401 Fsp3:   0.533
MCE-18:   25.826
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.018 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.06
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.032
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.031 Promiscuous compounds:   0.23

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.872 MDCK Permeability:   -5.065
Pgp-inhibitor:   0.0 Pgp-substrate:   0.003
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):   0.0
20% Bioavailability (F20%):   0.007 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.018

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.998
Plasma Protein Binding (PPB):   33.898% Volume Distribution (VD):   -0.601
Fu: 61.975%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.827
OATP1B3 inhibitor:   0.864 BCRP inhibitor:   0.0
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.978 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.0
?
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):  1.299 Half-life (T1/2):  1.617

ADMET: Toxicity

hERG Blockers:  0.002 hERG Blockers (10um):  0.002
Human Hepatotoxicity (H-HT):  0.595 Drug-induced Liver Injury (DILI):  0.889
AMES Toxicity:  0.054 Rat Oral Acute Toxicity:  0.423
Maximum Recommended Daily Dose:  0.08 Skin Sensitization:  0.966
Carcinogencity:  0.031 Eye Corrosion:  0.315
Eye Irritation:  0.834 Respiratory Toxicity:  0.522
Drug-induced Neurotoxicity:  0.041 Ototoxicity:  0.828
Hematotoxicity:  0.675 Drug-induced Nephrotoxicity:  0.98
Genotoxicity:  0.751 RPMI-8226 Immunitoxicity:  0.021
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.001
BCF:   0.049
?
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:   2.803
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.991
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.465
?
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
NPO28122 Senecio chionophilus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[15387646]
NPO28539 Xestospongia vanilla Species Petrosiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21945 Amomum melegueta Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27889 Anacyclus monanthos Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28505 Arum palaestinum Species Araceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28331 Astragalus siculus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28645 Chondria armata Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28403 Comanthus bennetti Species Comatulidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28105 Coriolopsis gallica Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28082 Corydalis tashiroi Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27969 Elvira biflora Species Trochilidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28493 Euphorbia cuneata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28522 Flustra denticulata Species Flustridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28420 Guizotia scabra Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28314 Hakea trifurcata Species Proteaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12214 Leontice robustum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28279 Mikania cordifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28156 Nezara viridula Species Pentatomidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27701 Otholobium glandulosum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28030 Polysiphonia nigra Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28227 Prunus speciosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27849 Raoulia australis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28122 Senecio chionophilus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27768 Terminalia brachystemma Species Combretaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27917 Ulmus campestris Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12214 Leontice robustum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28645 Chondria armata Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28645 Chondria armata Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12214 Leontice robustum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12214 Leontice robustum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28331 Astragalus siculus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28522 Flustra denticulata Species Flustridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28493 Euphorbia cuneata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21945 Amomum melegueta Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28314 Hakea trifurcata Species Proteaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28645 Chondria armata Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27917 Ulmus campestris Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12214 Leontice robustum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28030 Polysiphonia nigra Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27889 Anacyclus monanthos Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28403 Comanthus bennetti Species Comatulidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28420 Guizotia scabra Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27969 Elvira biflora Species Trochilidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28156 Nezara viridula Species Pentatomidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28122 Senecio chionophilus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28082 Corydalis tashiroi Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28105 Coriolopsis gallica Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27701 Otholobium glandulosum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28539 Xestospongia vanilla Species Petrosiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27768 Terminalia brachystemma Species Combretaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27849 Raoulia australis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28505 Arum palaestinum Species Araceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28279 Mikania cordifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28227 Prunus speciosa Species Rosaceae 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
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 16360.1 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 23109.3 nM PubChem BioAssay data set
NPT55 Individual protein Putative fructose-1,6-bisphosphate aldolase Giardia intestinalis Potency = 17740.7 nM PubChem BioAssay data set
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT67 Individual protein Cholinesterase Equus caballus Inhibition = 2.83 % PMID[23062825]
NPT93 Individual protein Survival motor neuron protein Homo sapiens Potency = 891.3 nM PubChem BioAssay data set
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 22387.2 nM PubChem BioAssay data set
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Inhibition = -14.36 % PMID[23062825]
NPT197 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT56 Individual protein Beta-lactamase AmpC Escherichia coli K-12 Potency = 50118.7 nM PubChem BioAssay data set
NPT532 Individual protein Lysine-specific demethylase 4A Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 79432.8 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 6513.1 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency n.a. 28183.8 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
- Rattus norvegicus NOEL = 5.0 mg/kg-day ToxVal
- Homo sapiens LOAEL = 0.9 mg/kg-day ToxVal
- Macaca mulatta LOAEL = 5.0 mg/kg-day ToxVal

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 NPC40663 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
0.6279 Remote Similarity NPC90476
0.6279 Remote Similarity NPC69374

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC40663 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