Natural Product: NPC270637

Natural Product IDNPC270637
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2,3,5-Trimethylpyrazine
IUPAC Name 2,3,5-trimethylpyrazine
Synonyms 2,3,5-Trimethyl-Pyrazine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL320146
PubChem CID 26808
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001346] Diazines
        • [CHEMONTID:0000067] Pyrazines

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 IAEGWXHKWJGQAZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C7H10N2/c1-5-4-8-6(2)7(3)9-5/h4H,1-3H3
SMILES Cc1cnc(C)c(C)n1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   122.08 Volume:   135.156
?
Van der Waals volume.
Dense:   0.903 LogP:   0.914
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.902
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   0.016
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   6.0
TPSA:   25.78
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.519 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.23 Fsp3:   0.429
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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.009 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.13
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.014
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.436 Promiscuous compounds:   0.03

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.919 MDCK Permeability:   -4.781
Pgp-inhibitor:   0.268 Pgp-substrate:   0.342
PAMPA:   0.465
?
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%):   0.074 30% Bioavailability (F30%):   0.07
50% Bioavailability (F50%):   0.492

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.868 MRP1:   0.964
Plasma Protein Binding (PPB):   66.752% Volume Distribution (VD):   0.08
Fu: 25.785%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.868
OATP1B3 inhibitor:   0.702 BCRP inhibitor:   0.024
BSEP inhibitor:   0.336

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.94 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.99 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.987 CYP2D6-substrate:   0.046
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.057 CYP2C8-inhibitor:   0.0
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):  8.339 Half-life (T1/2):  2.219

ADMET: Toxicity

hERG Blockers:  0.12 hERG Blockers (10um):  0.403
Human Hepatotoxicity (H-HT):  0.66 Drug-induced Liver Injury (DILI):  0.42
AMES Toxicity:  0.57 Rat Oral Acute Toxicity:  0.567
Maximum Recommended Daily Dose:  0.28 Skin Sensitization:  0.842
Carcinogencity:  0.802 Eye Corrosion:  0.752
Eye Irritation:  0.988 Respiratory Toxicity:  0.693
Drug-induced Neurotoxicity:  0.621 Ototoxicity:  0.309
Hematotoxicity:  0.365 Drug-induced Nephrotoxicity:  0.36
Genotoxicity:  0.161 RPMI-8226 Immunitoxicity:  0.076
A549 Cytotoxicity:  0.025 Hek293 Cytotoxicity:  0.05
BCF:   0.286
?
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:   2.216
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.169
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.547
?
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
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. n.a. DOI[10.1002/hlca.19270100148]
NPO17823 Lycium chinense Species Solanaceae Eukaryota fruits n.a. n.a. PMID[12467621]
NPO9445 Crocus sativus Species Iridaceae Eukaryota Petals n.a. n.a. PMID[15043425]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. root n.a. PMID[16212233]
NPO26969 Sagittaria sagittifolia Species Alismataceae Eukaryota n.a. n.a. n.a. PMID[16499326]
NPO8650 Perilla frutescens Species Lamiaceae Eukaryota leaves n.a. n.a. PMID[22272932]
NPO17823 Lycium chinense Species Solanaceae Eukaryota root bark n.a. n.a. PMID[23282106]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24014097]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24128451]
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[24338885]
NPO8650 Perilla frutescens Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[25320841]
NPO17823 Lycium chinense Species Solanaceae Eukaryota Root Bark n.a. n.a. PMID[26982999]
NPO23429 Lycium barbarum Species Solanaceae Eukaryota n.a. n.a. n.a. PMID[31397570]
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[37111302]
NPO23429 Lycium barbarum Species Solanaceae Eukaryota n.a. n.a. n.a. PMID[37446592]
NPO23429 Lycium barbarum Species Solanaceae Eukaryota n.a. n.a. n.a. PMID[38961030]
NPO17823 Lycium chinense Species Solanaceae Eukaryota fruits n.a. n.a. PMID[9090870]
NPO27018 Cynomorium songaricum Species Cynomoriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23429 Lycium barbarum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8650 Perilla frutescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19048 Pinellia ternata Species Araceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26969 Sagittaria sagittifolia Species Alismataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO9445 Crocus sativus Species Iridaceae Eukaryota Silk Stigma Style n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Sprout Seedling n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO27018 Cynomorium songaricum Species Cynomoriaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23429 Lycium barbarum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19048 Pinellia ternata Species Araceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26969 Sagittaria sagittifolia Species Alismataceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8650 Perilla frutescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27018 Cynomorium songaricum Species Cynomoriaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8650 Perilla frutescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23429 Lycium barbarum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19048 Pinellia ternata Species Araceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26969 Sagittaria sagittifolia Species Alismataceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26969 Sagittaria sagittifolia Species Alismataceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23429 Lycium barbarum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27018 Cynomorium songaricum Species Cynomoriaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8650 Perilla frutescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19048 Pinellia ternata Species Araceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8650 Perilla frutescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19048 Pinellia ternata Species Araceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27018 Cynomorium songaricum Species Cynomoriaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23429 Lycium barbarum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26969 Sagittaria sagittifolia Species Alismataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19048 Pinellia ternata Species Araceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9445 Crocus sativus Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23429 Lycium barbarum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8650 Perilla frutescens Species Lamiaceae 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
NPO7576 Brassica oleracea Other Stem 0.006 0.006 0.006 mg/100g Database [DUKE]

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
NPT2 Others Unspecified n.a. Potency n.a. 3238.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 32108 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 71880.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 28616.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 57586.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 508.9 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
- Rattus norvegicus LD50 = 806.0 mg/kg 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 NPC270637 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
0.6471 Remote Similarity NPC204104
0.5417 Remote Similarity NPC277608
0.5294 Remote Similarity NPC284039
0.5263 Remote Similarity NPC100312

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC270637 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
0.5294 Remote Similarity NPD9394 Clinical (unspecified phase)

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