Natural Product: NPC59269

Natural Product IDNPC59269
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Fellutanine A
IUPAC Name (3S,6S)-3,6-bis(1H-indol-3-ylmethyl)piperazine-2,5-dione
Synonyms Cyclo(-Trp-Trp)
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL191011
PubChem CID 7091706
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 DNHODRZUCGXYKU-PMACEKPBSA-N
Standard InCHI InChI=1S/C22H20N4O2/c27-21-19(9-13-11-23-17-7-3-1-5-15(13)17)25-22(28)20(26-21)10-14-12-24-18-8-4-2-6-16(14)18/h1-8,11-12,19-20,23-24H,9-10H2,(H,25,28)(H,26,27)/t19-,20-/m0/s1
SMILES c1ccc2c(c1)c(C[C@H]1C(=N[C@@H](Cc3c[nH]c4ccccc34)C(=N1)O)O)c[nH]2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.16 Volume:   381.489
?
Van der Waals volume.
Dense:   0.976 LogP:   2.28
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.99
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.255
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   26.0
TPSA:   96.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.434 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.591 Fsp3:   0.182
MCE-18:   78.846
?
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:   0.855 Fluc inhibitor:   0.465
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.161
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.444
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.043 Promiscuous compounds:   0.46

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.914 MDCK Permeability:   -4.696
Pgp-inhibitor:   0.682 Pgp-substrate:   0.798
PAMPA:   0.438
?
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):   0.179
20% Bioavailability (F20%):   0.912 30% Bioavailability (F30%):   0.99
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.081 MRP1:   0.341
Plasma Protein Binding (PPB):   72.282% Volume Distribution (VD):   -0.016
Fu: 28.602%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.912
OATP1B3 inhibitor:   0.892 BCRP inhibitor:   0.755
BSEP inhibitor:   0.966

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.87
CYP2C19-inhibitor:   0.06 CYP2C19-substrate:   0.828
CYP2C9-inhibitor:   0.991 CYP2C9-substrate:   0.027
CYP2D6-inhibitor:   0.994 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.949 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.846
HLM stability:   0.996
?
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):  3.793 Half-life (T1/2):  0.894

ADMET: Toxicity

hERG Blockers:  0.042 hERG Blockers (10um):  0.067
Human Hepatotoxicity (H-HT):  1.0 Drug-induced Liver Injury (DILI):  0.999
AMES Toxicity:  0.251 Rat Oral Acute Toxicity:  0.953
Maximum Recommended Daily Dose:  0.807 Skin Sensitization:  1.0
Carcinogencity:  0.211 Eye Corrosion:  0.0
Eye Irritation:  0.155 Respiratory Toxicity:  0.812
Drug-induced Neurotoxicity:  0.364 Ototoxicity:  0.932
Hematotoxicity:  0.826 Drug-induced Nephrotoxicity:  0.999
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.004
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.018
BCF:   0.95
?
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:   3.697
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.737
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.433
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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
NPO19211 Penicillium fellutanum Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[10843594]
NPO19211 Penicillium fellutanum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19211 Penicillium fellutanum Species Aspergillaceae 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[11858752]

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[23190013]
NPT179 Cell line A2780 Homo sapiens IC50 > 100000.0 nM PMID[20231393]

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 NPC59269 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 NPC282231
0.8511 High Similarity NPC63751
0.8333 Intermediate Similarity NPC54988
0.8 Intermediate Similarity NPC49954
0.7755 Intermediate Similarity NPC279918
0.7692 Intermediate Similarity NPC192615
0.6897 Remote Similarity NPC160105
0.6364 Remote Similarity NPC11126
0.62 Remote Similarity NPC190296
0.6047 Remote Similarity NPC601214
0.5938 Remote Similarity NPC145333
0.587 Remote Similarity NPC279081
0.5833 Remote Similarity NPC228835
0.5741 Remote Similarity NPC267885
0.5738 Remote Similarity NPC17059
0.5735 Remote Similarity NPC314603
0.5714 Remote Similarity NPC487314
0.5714 Remote Similarity NPC310665
0.5714 Remote Similarity NPC605863
0.5652 Remote Similarity NPC96102
0.5571 Remote Similarity NPC34779
0.5556 Remote Similarity NPC471957
0.5556 Remote Similarity NPC193761
0.5532 Remote Similarity NPC230869
0.549 Remote Similarity NPC78020
0.5479 Remote Similarity NPC486528
0.5455 Remote Similarity NPC480549
0.5417 Remote Similarity NPC29886
0.5385 Remote Similarity NPC315555
0.5385 Remote Similarity NPC55772
0.5345 Remote Similarity NPC248454
0.5333 Remote Similarity NPC194640
0.5306 Remote Similarity NPC84911
0.5283 Remote Similarity NPC149155
0.5283 Remote Similarity NPC203468
0.5283 Remote Similarity NPC110500
0.5283 Remote Similarity NPC605329
0.5273 Remote Similarity NPC608269
0.5263 Remote Similarity NPC213629
0.5254 Remote Similarity NPC259644
0.5254 Remote Similarity NPC70922
0.5254 Remote Similarity NPC211572
0.5254 Remote Similarity NPC75540
0.5254 Remote Similarity NPC212376
0.5254 Remote Similarity NPC469765
0.5254 Remote Similarity NPC80597
0.5254 Remote Similarity NPC25008
0.5254 Remote Similarity NPC73952
0.52 Remote Similarity NPC73767
0.5185 Remote Similarity NPC14113
0.5185 Remote Similarity NPC145885
0.5185 Remote Similarity NPC480318
0.5185 Remote Similarity NPC84827
0.5172 Remote Similarity NPC480548
0.5161 Remote Similarity NPC478795
0.5161 Remote Similarity NPC470499
0.5094 Remote Similarity NPC600736
0.5091 Remote Similarity NPC248041
0.5088 Remote Similarity NPC602670
0.5082 Remote Similarity NPC163055
0.5065 Remote Similarity NPC487596

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59269 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
0.623 Remote Similarity NPD6595 Phase 4
0.6129 Remote Similarity NPD4184 Phase 2
0.5652 Remote Similarity NPD198 Clinical (unspecified phase)
0.5385 Remote Similarity NPD4862 Clinical (unspecified phase)
0.5283 Remote Similarity NPD482 Phase 4
0.5185 Remote Similarity NPD749 Clinical (unspecified phase)
0.5128 Remote Similarity NPD8110 Clinical (unspecified phase)
0.5098 Remote Similarity NPD786 Pre-clinical

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