Natural Product: NPC17059

Natural Product IDNPC17059
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Brevianamide F
IUPAC Name (3S,8aS)-3-(1H-indol-3-ylmethyl)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Synonyms Brevianamide F
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL563557
PubChem CID 181567
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 RYFZBPVMVYTEKZ-KBPBESRZSA-N
Standard InCHI InChI=1S/C16H17N3O2/c20-15-14-6-3-7-19(14)16(21)13(18-15)8-10-9-17-12-5-2-1-4-11(10)12/h1-2,4-5,9,13-14,17H,3,6-8H2,(H,18,20)/t13-,14-/m0/s1
SMILES OC1=N[C@@H](Cc2c[nH]c3c2cccc3)C(=O)N2[C@H]1CCC2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   283.13 Volume:   285.818
?
Van der Waals volume.
Dense:   0.991 LogP:   1.082
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.464
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.608
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   21.0
TPSA:   68.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.885 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.431 Fsp3:   0.375
MCE-18:   69.091
?
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:   0.325 Fluc inhibitor:   0.144
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.084
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.264
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.665

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.415 MDCK Permeability:   -4.845
Pgp-inhibitor:   0.975 Pgp-substrate:   0.997
PAMPA:   0.058
?
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):   0.221
20% Bioavailability (F20%):   0.978 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.02 MRP1:   0.749
Plasma Protein Binding (PPB):   62.133% Volume Distribution (VD):   0.006
Fu: 39.346%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.604
OATP1B3 inhibitor:   0.233 BCRP inhibitor:   0.612
BSEP inhibitor:   0.889

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.194
CYP2C19-inhibitor:   0.647 CYP2C19-substrate:   0.677
CYP2C9-inhibitor:   0.456 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.43
CYP3A4-inhibitor:   0.957 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.04
HLM stability:   0.237
?
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):  5.902 Half-life (T1/2):  1.701

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.078
Human Hepatotoxicity (H-HT):  1.0 Drug-induced Liver Injury (DILI):  0.997
AMES Toxicity:  0.196 Rat Oral Acute Toxicity:  0.633
Maximum Recommended Daily Dose:  0.912 Skin Sensitization:  1.0
Carcinogencity:  0.407 Eye Corrosion:  0.0
Eye Irritation:  0.826 Respiratory Toxicity:  0.981
Drug-induced Neurotoxicity:  0.535 Ototoxicity:  0.861
Hematotoxicity:  0.251 Drug-induced Nephrotoxicity:  0.771
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.004
A549 Cytotoxicity:  0.001 Hek293 Cytotoxicity:  0.015
BCF:   0.621
?
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:   3.3
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.629
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.1
?
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
NPO23788 Beauveria bassiana Species Cordycipitaceae Eukaryota n.a. n.a. n.a. PMID[ 36006216]
NPO23788 Beauveria bassiana Species Cordycipitaceae Eukaryota n.a. n.a. n.a. PMID[16124776]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17616609]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17929896]
NPO23788 Beauveria bassiana Species Cordycipitaceae Eukaryota n.a. n.a. n.a. PMID[18804027]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19113967]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19159274]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19256529]
NPO23788 Beauveria bassiana Species Cordycipitaceae Eukaryota n.a. n.a. n.a. PMID[20233596]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. isolated from sediment collected using a hand held deep water sampling device at >33 m depth in Vanuatu 2003 PMID[20303767]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21667925]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21954885]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22106303]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota stem bark of Melia azedarach n.a. n.a. PMID[22409377]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23557488]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23563483]
NPO41486 Streptomyces bullii + Aspergillus fumigatus Species n.a. n.a. n.a. n.a. n.a. PMID[31953204]
NPO23788 Beauveria bassiana Species Cordycipitaceae Eukaryota n.a. n.a. n.a. PMID[32058711]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[7622436]
NPO23788 Beauveria bassiana Species Cordycipitaceae Eukaryota n.a. n.a. n.a. PMID[8557595]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23788 Beauveria bassiana Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23788 Beauveria bassiana Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23788 Beauveria bassiana Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23788 Beauveria bassiana Species Cordycipitaceae 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
NPT2960 Individual protein Brevianamide F prenyltransferase Aspergillus fumigatus Kcat = 5.57 /s PMID[19113967]
NPT2960 Individual protein Brevianamide F prenyltransferase Aspergillus fumigatus Ratio = 675.0 n.a. PMID[15771418]

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[18591275]
NPT165 Cell line HeLa Homo sapiens IC50 > 200000.0 nM PMID[21073160]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 11.9 ug.mL-1 PMID[21109433]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 44100.0 nM PMID[33153766]
NPT20 Organism Candida albicans Candida albicans IZ = 25.0 mm PMID[33153766]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 12.6 ug.mL-1 PMID[21109433]
NPT19 Organism Escherichia coli Escherichia coli MIC > 20.0 ug.mL-1 PMID[15387641]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus IZ = 19.0 mm PMID[33153766]

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 LC50 = 83.7 ug.mL-1 PMID[15730257]

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 NPC17059 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
0.7344 Intermediate Similarity NPC228835
0.7143 Intermediate Similarity NPC489625
0.7097 Intermediate Similarity NPC11126
0.6528 Remote Similarity NPC91179
0.6437 Remote Similarity NPC54420
0.6296 Remote Similarity NPC213629
0.6111 Remote Similarity NPC162860
0.6044 Remote Similarity NPC54744
0.6 Remote Similarity NPC293917
0.5934 Remote Similarity NPC284549
0.593 Remote Similarity NPC107077
0.5738 Remote Similarity NPC59269
0.573 Remote Similarity NPC223791
0.5667 Remote Similarity NPC31385
0.5634 Remote Similarity NPC602245
0.5634 Remote Similarity NPC606412
0.5632 Remote Similarity NPC171317
0.5543 Remote Similarity NPC110602
0.5543 Remote Similarity NPC479071
0.5455 Remote Similarity NPC480300
0.5426 Remote Similarity NPC479075
0.5397 Remote Similarity NPC285926
0.5397 Remote Similarity NPC14672
0.5393 Remote Similarity NPC483341
0.5368 Remote Similarity NPC482001
0.5362 Remote Similarity NPC49954
0.5312 Remote Similarity NPC479065
0.5303 Remote Similarity NPC282231
0.5263 Remote Similarity NPC155143
0.5258 Remote Similarity NPC479073
0.525 Remote Similarity NPC303658
0.5204 Remote Similarity NPC479076
0.5152 Remote Similarity NPC479066
0.5147 Remote Similarity NPC63751
0.5147 Remote Similarity NPC279918
0.51 Remote Similarity NPC75726
0.5094 Remote Similarity NPC325976
0.5094 Remote Similarity NPC326363
0.5075 Remote Similarity NPC480549
0.5072 Remote Similarity NPC54988
0.5072 Remote Similarity NPC480548
0.5047 Remote Similarity NPC489555

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC17059 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 NPD7621 Clinical (unspecified phase)
0.5152 Remote Similarity NPD7711 Discontinued
0.5056 Remote Similarity NPD7619 Phase 3

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