Natural Product: NPC233380

Natural Product IDNPC233380
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Aldisin
IUPAC Name 1,5,6,7-tetrahydropyrrolo[2,3-c]azepine-4,8-dione
Synonyms Aldisin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL357047
PubChem CID 3085877
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001990] Pyrroloazepines

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 AAPGLCCSVSGLFH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C8H8N2O2/c11-6-2-4-10-8(12)7-5(6)1-3-9-7/h1,3,9H,2,4H2,(H,10,12)
SMILES c1c[nH]c2c1C(=O)CCNC2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   164.06 Volume:   158.84
?
Van der Waals volume.
Dense:   1.033 LogP:   -0.076
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.203
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.744
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   13.0
TPSA:   61.96
?
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:   0.58 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.017 Fsp3:   0.25
MCE-18:   24.0
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.047 Fluc inhibitor:   0.052
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.178
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.152
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.009 Promiscuous compounds:   0.426

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.935 MDCK Permeability:   -4.636
Pgp-inhibitor:   0.739 Pgp-substrate:   0.484
PAMPA:   0.697
?
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):   0.18
20% Bioavailability (F20%):   0.008 30% Bioavailability (F30%):   0.1
50% Bioavailability (F50%):   0.557

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.14 MRP1:   0.607
Plasma Protein Binding (PPB):   3.022% Volume Distribution (VD):   -0.166
Fu: 91.807%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.719
OATP1B3 inhibitor:   0.924 BCRP inhibitor:   0.418
BSEP inhibitor:   0.32

ADMET: Metabolism

CYP1A2-inhibitor:   0.715 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.034
HLM stability:   0.337
?
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):  7.352 Half-life (T1/2):  2.16

ADMET: Toxicity

hERG Blockers:  0.04 hERG Blockers (10um):  0.254
Human Hepatotoxicity (H-HT):  0.575 Drug-induced Liver Injury (DILI):  0.633
AMES Toxicity:  0.872 Rat Oral Acute Toxicity:  0.512
Maximum Recommended Daily Dose:  0.271 Skin Sensitization:  0.736
Carcinogencity:  0.844 Eye Corrosion:  0.034
Eye Irritation:  0.964 Respiratory Toxicity:  0.478
Drug-induced Neurotoxicity:  0.764 Ototoxicity:  0.372
Hematotoxicity:  0.755 Drug-induced Nephrotoxicity:  0.57
Genotoxicity:  0.988 RPMI-8226 Immunitoxicity:  0.098
A549 Cytotoxicity:  0.075 Hek293 Cytotoxicity:  0.122
BCF:   0.128
?
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:   2.259
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.179
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.948
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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
NPO7079 Stylissa massa Species Axinellidae Eukaryota n.a. Philippine n.a. PMID[11784156]
NPO7079 Stylissa massa Species Axinellidae Eukaryota n.a. n.a. n.a. PMID[12816422]
NPO32816 Axinella carteri Species Axinellidae Eukaryota n.a. n.a. n.a. PMID[15043426]
NPO7079 Stylissa massa Species Axinellidae Eukaryota n.a. n.a. n.a. PMID[23684893]
NPO32816 Axinella carteri Species Axinellidae Eukaryota n.a. Chuuk Atoll, Federated States of Micronesia n.a. PMID[9548881]
NPO8562 Echinocystis fabacea Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3926 Ptilometra australis Species Ptilometridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7079 Stylissa massa Species Axinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6961 Vernonia arctioides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO32816 Axinella carteri Species Axinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6961 Vernonia arctioides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3926 Ptilometra australis Species Ptilometridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8562 Echinocystis fabacea Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7079 Stylissa massa Species Axinellidae 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
NPT282 Individual protein MAP kinase ERK2 Homo sapiens IC50 > 2500.0 nM PMID[11784156]
NPT490 Protein family Serine/threonine-protein kinase RAF and Dual specificity mitogen-activated protein kinase kinase 1 (Raf/MEK) Homo sapiens IC50 > 2500.0 nM PMID[11784156]
NPT491 Individual protein Dual specificity mitogen-activated protein kinase kinase 1 Homo sapiens IC50 = 2500.0 nM PMID[11784156]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT492 Cell line Caco-2 Homo sapiens IC50 > 10000.0 nM PMID[11784156]
NPT114 Cell line LoVo Homo sapiens IC50 > 10000.0 nM PMID[11784156]
NPT81 Cell line A549 Homo sapiens GI50 > 100000.0 nM PMID[22995819]
NPT114 Cell line LoVo Homo sapiens GI50 > 100000.0 nM PMID[22995819]
NPT83 Cell line MCF7 Homo sapiens GI50 > 100000.0 nM PMID[22995819]
NPT306 Cell line PC-3 Homo sapiens GI50 > 100000.0 nM PMID[22995819]

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 NPC233380 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
0.5745 Remote Similarity NPC2414

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC233380 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
NPD

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