Natural Product: NPC242159

Natural Product IDNPC242159
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cyclo-L-Pro-L-Tyr
IUPAC Name (3S,8aS)-3-[(4-hydroxyphenyl)methyl]-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL359788
PubChem CID 119404
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:0000060] Alpha amino acids and derivatives

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 LSGOTAXPWMCUCK-RYUDHWBXSA-N
Standard InCHI InChI=1S/C14H16N2O3/c17-10-5-3-9(4-6-10)8-11-14(19)16-7-1-2-12(16)13(18)15-11/h3-6,11-12,17H,1-2,7-8H2,(H,15,18)/t11-,12-/m0/s1
SMILES Oc1ccc(cc1)C[C@@H]1N=C(O)[C@H]2N(C1=O)CCC2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.12 Volume:   260.213
?
Van der Waals volume.
Dense:   1.0 LogP:   0.065
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.822
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.143
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   73.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.841 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.4 Fsp3:   0.429
MCE-18:   56.0
?
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:   0.31 Fluc inhibitor:   0.005
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.284
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.004 Promiscuous compounds:   0.205

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.12 MDCK Permeability:   -4.662
Pgp-inhibitor:   0.694 Pgp-substrate:   0.989
PAMPA:   0.162
?
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):   0.125
20% Bioavailability (F20%):   0.989 30% Bioavailability (F30%):   0.991
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.807
Plasma Protein Binding (PPB):   57.528% Volume Distribution (VD):   -0.059
Fu: 40.578%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.895
OATP1B3 inhibitor:   0.536 BCRP inhibitor:   0.425
BSEP inhibitor:   0.877

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.064
CYP2C19-inhibitor:   0.255 CYP2C19-substrate:   0.855
CYP2C9-inhibitor:   0.037 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.879 CYP3A4-substrate:   0.005
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.007
HLM stability:   0.735
?
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):  10.173 Half-life (T1/2):  1.692

ADMET: Toxicity

hERG Blockers:  0.011 hERG Blockers (10um):  0.031
Human Hepatotoxicity (H-HT):  1.0 Drug-induced Liver Injury (DILI):  0.993
AMES Toxicity:  0.059 Rat Oral Acute Toxicity:  0.691
Maximum Recommended Daily Dose:  0.978 Skin Sensitization:  1.0
Carcinogencity:  0.103 Eye Corrosion:  0.0
Eye Irritation:  0.914 Respiratory Toxicity:  0.993
Drug-induced Neurotoxicity:  0.759 Ototoxicity:  0.768
Hematotoxicity:  0.09 Drug-induced Nephrotoxicity:  0.7
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.002
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.042
BCF:   0.866
?
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:   3.495
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.523
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.022
?
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
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. mycelium n.a. PMID[10423860]
NPO21926 Pseudomonas aeruginosa Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[10556916]
NPO1520 Callyspongia pseudoreticulata Species Callyspongiidae Eukaryota n.a. n.a. n.a. PMID[12828480]
NPO24252 Uvaria hamiltonii Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[14552774]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. n.a. n.a. PMID[15863936]
NPO21926 Pseudomonas aeruginosa Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[19406895]
NPO33480 leptoxyphium sp. Species Capnodiaceae Eukaryota n.a. n.a. n.a. PMID[19637889]
NPO21926 Pseudomonas aeruginosa Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[19917748]
NPO2605 Pichia membranifaciens Species Pichiaceae Eukaryota n.a. n.a. n.a. PMID[19943625]
NPO21926 Pseudomonas aeruginosa Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[20932054]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. mycelium n.a. PMID[21848266]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. n.a. n.a. PMID[21848266]
NPO21926 Pseudomonas aeruginosa Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[25043228]
NPO21926 Pseudomonas aeruginosa Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[25960261]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota Roots n.a. n.a. PMID[32004936]
NPO21926 Pseudomonas aeruginosa Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[32603106]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[39053741]
NPO21926 Pseudomonas aeruginosa Species Pseudomonadaceae Bacteria n.a. Antarctic n.a. PMID[8882433]
NPO24252 Uvaria hamiltonii Species Annonaceae Eukaryota leaf and stem n.a. n.a. PMID[9584399]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21926 Pseudomonas aeruginosa Species Pseudomonadaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO2605 Pichia membranifaciens Species Pichiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24252 Uvaria hamiltonii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23277 Lobophora papenfussii Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2605 Pichia membranifaciens Species Pichiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24585 Ocotea macropoda Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23277 Lobophora papenfussii Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1520 Callyspongia pseudoreticulata Species Callyspongiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23819 Baccharis peruviana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28694 Sanguisorba tenuifolia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24252 Uvaria hamiltonii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21926 Pseudomonas aeruginosa Species Pseudomonadaceae Bacteria 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
NPT3966 Individual protein Phenol oxidase Plutella xylostella IC50 = 42480.0 nM PMID[22447611]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2779 Organism Spodoptera exigua Spodoptera exigua IC50 = 37710.0 nM PMID[22447611]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Cell aggregates = 77.5 n.a. PMID[15509170]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Cell aggregates = 33.9 n.a. PMID[15509170]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 11.72 ug.mL-1 PMID[21848266]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 5.65 ug.mL-1 PMID[21848266]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 8.7 ug.mL-1 PMID[26099531]
NPT1 Others Radical scavenging activity n.a. Activity = 16.0 % PMID[19943625]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 10.2 ug.mL-1 PMID[26099531]
NPT19 Organism Escherichia coli Escherichia coli MIC > 20.0 ug.mL-1 PMID[26099531]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa Activity = 48.0 % PMID[35724567]
NPT2 Others Unspecified n.a. IC50 = 47790.0 nM PMID[22447611]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity = 40.0 % PMID[26988307]





 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
- Plutella xylostella LC50 = 5948.7 ppm PMID[22447611]

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 NPC242159 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
0.7551 Intermediate Similarity NPC285926
0.7551 Intermediate Similarity NPC14672
0.7377 Intermediate Similarity NPC242482
0.7258 Intermediate Similarity NPC224315
0.6923 Remote Similarity NPC16188
0.6667 Remote Similarity NPC202198
0.6567 Remote Similarity NPC489829
0.6164 Remote Similarity NPC136797
0.6032 Remote Similarity NPC200589
0.5789 Remote Similarity NPC485662
0.5789 Remote Similarity NPC141957
0.5789 Remote Similarity NPC485663
0.5789 Remote Similarity NPC241794
0.5714 Remote Similarity NPC481073
0.5641 Remote Similarity NPC481074
0.5606 Remote Similarity NPC262077
0.5405 Remote Similarity NPC489556
0.5366 Remote Similarity NPC489828
0.5345 Remote Similarity NPC175726
0.5345 Remote Similarity NPC474082
0.5286 Remote Similarity NPC489593
0.5278 Remote Similarity NPC489557
0.5263 Remote Similarity NPC5194
0.5263 Remote Similarity NPC488256
0.5263 Remote Similarity NPC56685
0.5238 Remote Similarity NPC328649
0.5067 Remote Similarity NPC489592
0.5063 Remote Similarity NPC101679
0.5063 Remote Similarity NPC261934
0.5063 Remote Similarity NPC488254

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC242159 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
0.5263 Remote Similarity NPD7118 Phase 2
0.5139 Remote Similarity NPD4791 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