Natural Product: NPC296742

Natural Product IDNPC296742
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Aristolactam I
IUPAC Name n.a.
Synonyms Aristolactam I
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479127
PubChem CID 96710
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002663] Aristolactams

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 MXOKGWUJNGEKBH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H11NO4/c1-20-12-4-2-3-8-9(12)5-11-14-10(17(19)18-11)6-13-16(15(8)14)22-7-21-13/h2-6H,7H2,1H3,(H,18,19)
SMILES COc1cccc2c1cc1c3c(cc4c(c23)OCO4)C(=N1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   293.07 Volume:   284.872
?
Van der Waals volume.
Dense:   1.029 LogP:   3.522
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.102
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.274
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   60.28
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.695 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.0 Fsp3:   0.118
MCE-18:   52.632
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.948 Fluc inhibitor:   0.649
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.932
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.578
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.009 Promiscuous compounds:   0.493

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.929 MDCK Permeability:   -4.78
Pgp-inhibitor:   0.288 Pgp-substrate:   0.628
PAMPA:   0.587
?
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):   0.324
20% Bioavailability (F20%):   0.365 30% Bioavailability (F30%):   0.241
50% Bioavailability (F50%):   0.628

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.071 MRP1:   0.833
Plasma Protein Binding (PPB):   98.759% Volume Distribution (VD):   -0.521
Fu: 1.152%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.61
OATP1B3 inhibitor:   0.763 BCRP inhibitor:   0.15
BSEP inhibitor:   0.804

ADMET: Metabolism

CYP1A2-inhibitor:   0.994 CYP1A2-substrate:   0.856
CYP2C19-inhibitor:   0.973 CYP2C19-substrate:   0.676
CYP2C9-inhibitor:   0.99 CYP2C9-substrate:   0.8
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.889
CYP3A4-inhibitor:   0.008 CYP3A4-substrate:   0.849
CYP2B6-substrate:   0.384 CYP2C8-inhibitor:   0.003
HLM stability:   0.298
?
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):  3.888 Half-life (T1/2):  0.759

ADMET: Toxicity

hERG Blockers:  0.2 hERG Blockers (10um):  0.341
Human Hepatotoxicity (H-HT):  0.875 Drug-induced Liver Injury (DILI):  0.992
AMES Toxicity:  0.866 Rat Oral Acute Toxicity:  0.58
Maximum Recommended Daily Dose:  0.668 Skin Sensitization:  0.522
Carcinogencity:  0.877 Eye Corrosion:  0.0
Eye Irritation:  0.82 Respiratory Toxicity:  0.896
Drug-induced Neurotoxicity:  0.647 Ototoxicity:  0.68
Hematotoxicity:  0.838 Drug-induced Nephrotoxicity:  0.865
Genotoxicity:  0.723 RPMI-8226 Immunitoxicity:  0.135
A549 Cytotoxicity:  0.339 Hek293 Cytotoxicity:  0.496
BCF:   1.469
?
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:   3.762
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.684
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.658
?
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
NPO18443 Aristolochia manshuriensis Species Aristolochiaceae Eukaryota Stems n.a. n.a. PMID[12880323]
NPO14814 Aristolochia contorta Species Aristolochiaceae Eukaryota n.a. n.a. n.a. PMID[1431939]
NPO267 Couepia polyandra Species Chrysobalanaceae Eukaryota n.a. n.a. n.a. PMID[14640519]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota leaves Niigata City, Niigata Province, Japan 2000-Nov PMID[15730243]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota leaves n.a. n.a. PMID[16933868]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[17253842]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota stems and twigs Niigata City, Niigata Province, Japan 2001-NOV PMID[17595134]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota stems and twigs n.a. n.a. PMID[17595134]
NPO18443 Aristolochia manshuriensis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. PMID[20097074]
NPO18443 Aristolochia manshuriensis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. PMID[21353775]
NPO6336 Asarum sieboldii Species Aristolochiaceae Eukaryota roots n.a. n.a. PMID[22381047]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[29693393]
NPO30274 Pararistolochia flos-avis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. PMID[3437282]
NPO3961 Lavandula hybrida Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[39147955]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota Leaves; Stems n.a. n.a. PMID[9214727]
NPO7557 Aristolochia mollissima Species Aristolochiaceae Eukaryota n.a. amniotic fluid n.a. Database[Article]
NPO4533 Spatoglossum schmittii Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6336 Asarum sieboldii Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18443 Aristolochia manshuriensis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29078 Asiasarum sieboldii n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12468 Asarum heterotropoides Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4659 Asiasarum heterotropoides n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO7557 Aristolochia mollissima Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24916 Aristolochia debilis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27817 Stephania hernandifolia Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14814 Aristolochia contorta Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO267 Couepia polyandra Species Chrysobalanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14814 Aristolochia contorta Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18443 Aristolochia manshuriensis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27817 Stephania hernandifolia Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23020 Aristolochia fangchi Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24916 Aristolochia debilis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6336 Asarum sieboldii Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7557 Aristolochia mollissima Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30274 Pararistolochia flos-avis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6336 Asarum sieboldii Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7557 Aristolochia mollissima Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27817 Stephania hernandifolia Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24916 Aristolochia debilis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14814 Aristolochia contorta Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18443 Aristolochia manshuriensis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23020 Aristolochia fangchi Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6336 Asarum sieboldii Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23020 Aristolochia fangchi Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24916 Aristolochia debilis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27817 Stephania hernandifolia Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14814 Aristolochia contorta Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18443 Aristolochia manshuriensis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7557 Aristolochia mollissima Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12468 Asarum heterotropoides Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29078 Asiasarum sieboldii n.a. n.a. n.a. n.a. n.a. n.a. Database[TM-MC]
NPO4659 Asiasarum heterotropoides n.a. n.a. n.a. n.a. n.a. n.a. Database[TM-MC]
NPO12468 Asarum heterotropoides Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24916 Aristolochia debilis Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6336 Asarum sieboldii Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14814 Aristolochia contorta Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6336 Asarum sieboldii Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27817 Stephania hernandifolia Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO267 Couepia polyandra Species Chrysobalanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10021 Nerium oleander Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10846 Aristolochia rotunda Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3961 Lavandula hybrida Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23841 Dysophylla verticillata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO4659 Asiasarum heterotropoides n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO4533 Spatoglossum schmittii Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12468 Asarum heterotropoides Species Aristolochiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29078 Asiasarum sieboldii n.a. n.a. n.a. 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
NPT1371 Individual protein Cyclin-dependent kinase 2 Homo sapiens IC50 = 1200.0 nM PMID[20097066]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC296742 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
0.7895 Intermediate Similarity NPC224293
0.7544 Intermediate Similarity NPC478594
0.7458 Intermediate Similarity NPC29472
0.7368 Intermediate Similarity NPC69213
0.6533 Remote Similarity NPC159101
0.6154 Remote Similarity NPC112676
0.5932 Remote Similarity NPC265383
0.5522 Remote Similarity NPC603719
0.5469 Remote Similarity NPC77359
0.5397 Remote Similarity NPC260118
0.5303 Remote Similarity NPC192939
0.5077 Remote Similarity NPC118332
0.5075 Remote Similarity NPC215747

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC296742 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