Natural Product: NPC161972

Natural Product IDNPC161972
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cyclo(L-Phe-L-Leu)
IUPAC Name (3S,6S)-3-benzyl-6-(2-methylpropyl)piperazine-2,5-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL189999
PubChem CID 7076347
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 QPDMOMIYLJMOQJ-STQMWFEESA-N
Standard InCHI InChI=1S/C15H20N2O2/c1-10(2)8-12-14(18)17-13(15(19)16-12)9-11-6-4-3-5-7-11/h3-7,10,12-13H,8-9H2,1-2H3,(H,16,19)(H,17,18)/t12-,13-/m0/s1
SMILES CC(C)C[C@H]1C(=N[C@@H](Cc2ccccc2)C(=N1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.15 Volume:   277.275
?
Van der Waals volume.
Dense:   0.938 LogP:   1.623
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.89
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.239
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   65.18
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.874 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.587 Fsp3:   0.467
MCE-18:   38.182
?
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:   0.657 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.02
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.493
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.047 Promiscuous compounds:   0.12

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.121 MDCK Permeability:   -4.318
Pgp-inhibitor:   0.85 Pgp-substrate:   0.979
PAMPA:   0.43
?
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):   0.276
20% Bioavailability (F20%):   0.919 30% Bioavailability (F30%):   0.959
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.024 MRP1:   0.474
Plasma Protein Binding (PPB):   72.322% Volume Distribution (VD):   0.002
Fu: 29.452%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.915
OATP1B3 inhibitor:   0.486 BCRP inhibitor:   0.402
BSEP inhibitor:   0.924

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.025
CYP2C19-inhibitor:   0.155 CYP2C19-substrate:   0.94
CYP2C9-inhibitor:   0.753 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.001
HLM stability:   0.867
?
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):  4.127 Half-life (T1/2):  1.481

ADMET: Toxicity

hERG Blockers:  0.015 hERG Blockers (10um):  0.032
Human Hepatotoxicity (H-HT):  1.0 Drug-induced Liver Injury (DILI):  0.99
AMES Toxicity:  0.166 Rat Oral Acute Toxicity:  0.549
Maximum Recommended Daily Dose:  0.219 Skin Sensitization:  1.0
Carcinogencity:  0.213 Eye Corrosion:  0.0
Eye Irritation:  0.874 Respiratory Toxicity:  0.543
Drug-induced Neurotoxicity:  0.55 Ototoxicity:  0.778
Hematotoxicity:  0.322 Drug-induced Nephrotoxicity:  0.934
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.003
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.03
BCF:   0.549
?
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:   3.256
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.499
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.928
?
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
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.carres.2012.01.012]
NPO40546 Paecilomyces marquandii Species Clavicipitaceae Eukaryota n.a. n.a. n.a. PMID[17190466]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. PMID[26562741]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. PMID[29517238]
NPO40546 Paecilomyces marquandii Species Clavicipitaceae Eukaryota n.a. n.a. n.a. PMID[31432669]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. PMID[31625751]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota Roots n.a. n.a. PMID[32004936]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. Along the Valencian coast, Spain 2020-Jun&Jul PMID[35161358]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[39053741]
NPO40546 Paecilomyces marquandii Species Clavicipitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota Herb n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. Database[FooDB]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4554 Isatis tinctoria Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
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]

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
NPT3579 Individual protein Calpain 1 Homo sapiens Inhibition = 0.0 % PMID[15896956]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT79 Organism Bacillus subtilis Bacillus subtilis IZ = 10.0 mm PMID[17190466]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 23.5 % PMID[22356736]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 0.0 % PMID[22356736]
NPT19 Organism Escherichia coli Escherichia coli IZ = 8.0 mm PMID[17190466]

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 NPC161972 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
0.7442 Intermediate Similarity NPC118202
0.7429 Intermediate Similarity NPC311242
0.7179 Intermediate Similarity NPC303045
0.7073 Intermediate Similarity NPC25565
0.7073 Intermediate Similarity NPC475439
0.7 Intermediate Similarity NPC487313
0.6923 Remote Similarity NPC621
0.6731 Remote Similarity NPC487595
0.6481 Remote Similarity NPC487312
0.6481 Remote Similarity NPC237420
0.6275 Remote Similarity NPC486124
0.625 Remote Similarity NPC487311
0.6087 Remote Similarity NPC194390
0.6047 Remote Similarity NPC82963
0.6042 Remote Similarity NPC88267
0.58 Remote Similarity NPC224610
0.58 Remote Similarity NPC113326
0.5574 Remote Similarity NPC488609
0.5455 Remote Similarity NPC226438
0.5385 Remote Similarity NPC479068
0.5385 Remote Similarity NPC45777
0.537 Remote Similarity NPC254088
0.5273 Remote Similarity NPC479753
0.5231 Remote Similarity NPC46427
0.5192 Remote Similarity NPC100825
0.5179 Remote Similarity NPC49954
0.5147 Remote Similarity NPC479072
0.5128 Remote Similarity NPC180402
0.5116 Remote Similarity NPC38458
0.5116 Remote Similarity NPC311737
0.5075 Remote Similarity NPC485094
0.5072 Remote Similarity NPC489368
0.5072 Remote Similarity NPC484378

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC161972 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
0.5147 Remote Similarity NPD8265 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