Natural Product: NPC282231

Natural Product IDNPC282231
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 L-Alanyl-L-Tryptophan Anhydride
IUPAC Name (3S,6S)-3-(1H-indol-3-ylmethyl)-6-methylpiperazine-2,5-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2031511
PubChem CID 15563754
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 VDMMFAOUINDEGC-UFBFGSQYSA-N
Standard InCHI InChI=1S/C14H15N3O2/c1-8-13(18)17-12(14(19)16-8)6-9-7-15-11-5-3-2-4-10(9)11/h2-5,7-8,12,15H,6H2,1H3,(H,16,19)(H,17,18)/t8-,12-/m0/s1
SMILES OC1=N[C@@H](Cc2c[nH]c3c2cccc3)C(=N[C@H]1C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   257.12 Volume:   259.783
?
Van der Waals volume.
Dense:   0.99 LogP:   0.233
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.241
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.134
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   16.0
TPSA:   80.97
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.772 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.656 Fsp3:   0.286
MCE-18:   51.556
?
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:   0.408 Fluc inhibitor:   0.053
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.106
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.376
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.018 Promiscuous compounds:   0.668

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.425 MDCK Permeability:   -4.748
Pgp-inhibitor:   0.519 Pgp-substrate:   0.995
PAMPA:   0.487
?
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):   0.059
20% Bioavailability (F20%):   0.922 30% Bioavailability (F30%):   0.949
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.022 MRP1:   0.71
Plasma Protein Binding (PPB):   65.612% Volume Distribution (VD):   0.047
Fu: 34.789%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.871
OATP1B3 inhibitor:   0.798 BCRP inhibitor:   0.231
BSEP inhibitor:   0.932

ADMET: Metabolism

CYP1A2-inhibitor:   0.068 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.977 CYP2C19-substrate:   0.913
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.068 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.001
HLM stability:   0.3
?
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):  1.749 Half-life (T1/2):  1.846

ADMET: Toxicity

hERG Blockers:  0.02 hERG Blockers (10um):  0.038
Human Hepatotoxicity (H-HT):  1.0 Drug-induced Liver Injury (DILI):  0.986
AMES Toxicity:  0.222 Rat Oral Acute Toxicity:  0.772
Maximum Recommended Daily Dose:  0.372 Skin Sensitization:  1.0
Carcinogencity:  0.362 Eye Corrosion:  0.0
Eye Irritation:  0.617 Respiratory Toxicity:  0.624
Drug-induced Neurotoxicity:  0.328 Ototoxicity:  0.865
Hematotoxicity:  0.438 Drug-induced Nephrotoxicity:  0.895
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.004
A549 Cytotoxicity:  0.001 Hek293 Cytotoxicity:  0.011
BCF:   0.371
?
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:   3.092
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.504
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.708
?
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
NPO32990 acrostalagmus luteoalbus scsio f457 Species Plectosphaerellaceae Eukaryota n.a. n.a. n.a. PMID[23079524]
NPO33384 Nocardiopsis gilva YIM 90087 Species Nocardiopsaceae Bacteria n.a. n.a. n.a. PMID[23441911]
NPO32640 eurotium rubrum ma-150 Species Aspergillaceae Eukaryota Fungus Obtained from Marine Mangrove-Derived Rhizospheric Soil. n.a. n.a. PMID[25730346]

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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT111 Cell line K562 Homo sapiens IC50 > 100000.0 nM PMID[22617493]
NPT179 Cell line A2780 Homo sapiens IC50 > 100000.0 nM PMID[22617493]
NPT65 Cell line HepG2 Homo sapiens IC50 > 100000.0 nM PMID[23079524]
NPT397 Cell line NCI-H460 Homo sapiens IC50 > 100000.0 nM PMID[23079524]
NPT83 Cell line MCF7 Homo sapiens IC50 > 100000.0 nM PMID[23079524]
NPT395 Cell line SF-268 Homo sapiens IC50 > 100000.0 nM PMID[23079524]
NPT616 Cell line MDCK Canis lupus familiaris CC50 > 200000.0 nM PMID[25681711]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 54.6 % PMID[23441911]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 2.31 % PMID[25681711]

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
- Artemia salina LD50 = 25.5 uM PMID[25730346]

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 NPC282231 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
0.8889 High Similarity NPC59269
0.7759 Intermediate Similarity NPC160105
0.7692 Intermediate Similarity NPC63751
0.7593 Intermediate Similarity NPC49954
0.7547 Intermediate Similarity NPC54988
0.7037 Intermediate Similarity NPC279918
0.7018 Intermediate Similarity NPC192615
0.6167 Remote Similarity NPC194640
0.6102 Remote Similarity NPC11126
0.5926 Remote Similarity NPC190296
0.5738 Remote Similarity NPC285469
0.5714 Remote Similarity NPC213629
0.5625 Remote Similarity NPC228835
0.5625 Remote Similarity NPC171317
0.5556 Remote Similarity NPC314603
0.5541 Remote Similarity NPC487314
0.5517 Remote Similarity NPC267885
0.5507 Remote Similarity NPC145333
0.5417 Remote Similarity NPC601214
0.5405 Remote Similarity NPC34779
0.5395 Remote Similarity NPC193761
0.5303 Remote Similarity NPC17059
0.5294 Remote Similarity NPC279081
0.5254 Remote Similarity NPC480549
0.5192 Remote Similarity NPC29886
0.5185 Remote Similarity NPC310665
0.5185 Remote Similarity NPC605863
0.5161 Remote Similarity NPC248454
0.5128 Remote Similarity NPC486528
0.5125 Remote Similarity NPC487596
0.5114 Remote Similarity NPC479572
0.5114 Remote Similarity NPC479568
0.5114 Remote Similarity NPC479573
0.5114 Remote Similarity NPC479566
0.5114 Remote Similarity NPC479567
0.5114 Remote Similarity NPC479569
0.5114 Remote Similarity NPC479571
0.5098 Remote Similarity NPC96102
0.5085 Remote Similarity NPC471957
0.5085 Remote Similarity NPC608269
0.5079 Remote Similarity NPC259644
0.5079 Remote Similarity NPC70922
0.5079 Remote Similarity NPC211572
0.5079 Remote Similarity NPC75540
0.5079 Remote Similarity NPC212376
0.5079 Remote Similarity NPC469765
0.5079 Remote Similarity NPC80597
0.5079 Remote Similarity NPC25008
0.5079 Remote Similarity NPC73952
0.5056 Remote Similarity NPC479570
0.5056 Remote Similarity NPC155143

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC282231 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
0.6 Remote Similarity NPD6595 Phase 4
0.5909 Remote Similarity NPD4184 Phase 2
0.5488 Remote Similarity NPD8431 Pre-clinical
0.5441 Remote Similarity NPD4862 Clinical (unspecified phase)
0.5185 Remote Similarity NPD786 Pre-clinical
0.5114 Remote Similarity NPD8458 Clinical (unspecified phase)
0.5098 Remote Similarity NPD198 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