Natural Product: NPC304257

Natural Product IDNPC304257
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Purealidin J
IUPAC Name (5R,6S)-N-[2-(2-amino-1H-imidazol-5-yl)ethyl]-7,9-dibromo-6-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,7,9-triene-3-carboxamide
Synonyms Purealidin J
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464285
PubChem CID 10672719
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000436] Azoles
        • [CHEMONTID:0000078] Imidazoles
          • [CHEMONTID:0002310] Substituted imidazoles
            • [CHEMONTID:0001225] Aminoimidazoles

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 NBOVGEUANNHLCZ-DOMZBBRYSA-N
Standard InCHI InChI=1S/C15H17Br2N5O4/c1-25-11-8(16)4-15(12(23)10(11)17)5-9(22-26-15)13(24)19-3-2-7-6-20-14(18)21-7/h4,6,12,23H,2-3,5H2,1H3,(H,19,24)(H3,18,20,21)/t12-,15+/m1/s1
SMILES COC1=C(Br)[C@H]([C@@]2(C=C1Br)ON=C(C2)C(=O)NCCc1c[nH]c(=N)[nH]1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   488.96 Volume:   355.22
?
Van der Waals volume.
Dense:   1.376 LogP:   1.099
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.565
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.785
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   135.58
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Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.419 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.038 Fsp3:   0.4
MCE-18:   85.714
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.77 Fluc inhibitor:   0.134
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.071
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.571
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.054 Promiscuous compounds:   0.105

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.852 MDCK Permeability:   -4.805
Pgp-inhibitor:   0.31 Pgp-substrate:   0.91
PAMPA:   0.13
?
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):   0.02
20% Bioavailability (F20%):   0.151 30% Bioavailability (F30%):   0.568
50% Bioavailability (F50%):   0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.785
Plasma Protein Binding (PPB):   92.689% Volume Distribution (VD):   0.033
Fu: 7.009%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.957
OATP1B3 inhibitor:   0.638 BCRP inhibitor:   0.829
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.018 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.165
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.022
CYP3A4-inhibitor:   0.029 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.923
HLM stability:   0.068
?
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):  1.254 Half-life (T1/2):  2.94

ADMET: Toxicity

hERG Blockers:  0.136 hERG Blockers (10um):  0.476
Human Hepatotoxicity (H-HT):  0.978 Drug-induced Liver Injury (DILI):  0.958
AMES Toxicity:  0.991 Rat Oral Acute Toxicity:  0.966
Maximum Recommended Daily Dose:  0.911 Skin Sensitization:  1.0
Carcinogencity:  0.999 Eye Corrosion:  0.0
Eye Irritation:  0.662 Respiratory Toxicity:  0.998
Drug-induced Neurotoxicity:  0.845 Ototoxicity:  0.606
Hematotoxicity:  0.038 Drug-induced Nephrotoxicity:  0.828
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.033
A549 Cytotoxicity:  0.05 Hek293 Cytotoxicity:  0.913
BCF:   0.765
?
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:   3.511
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.181
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.579
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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
NPO33394 druinella sp. Species n.a. n.a. n.a. Fujian, China n.a. PMID[12502317]

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
NPT179 Cell line A2780 Homo sapiens ID50 > 10.0 ug ml-1 PMID[17190444]
NPT111 Cell line K562 Homo sapiens ID50 > 10.0 ug ml-1 PMID[23398362]

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 NPC304257 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
0.8028 Intermediate Similarity NPC181086
0.75 Intermediate Similarity NPC81079
0.7083 Intermediate Similarity NPC289324
0.6974 Remote Similarity NPC201900
0.6711 Remote Similarity NPC600759
0.6471 Remote Similarity NPC1702
0.6286 Remote Similarity NPC158672
0.6076 Remote Similarity NPC487872
0.6076 Remote Similarity NPC608122
0.6027 Remote Similarity NPC487917
0.5976 Remote Similarity NPC608121
0.5918 Remote Similarity NPC185172
0.5854 Remote Similarity NPC487873
0.5844 Remote Similarity NPC473262
0.5844 Remote Similarity NPC202166
0.5696 Remote Similarity NPC473261
0.5696 Remote Similarity NPC300912
0.5692 Remote Similarity NPC30521
0.55 Remote Similarity NPC145149
0.5455 Remote Similarity NPC202866
0.5432 Remote Similarity NPC313173
0.54 Remote Similarity NPC603907
0.5393 Remote Similarity NPC601097
0.5366 Remote Similarity NPC260270
0.5357 Remote Similarity NPC130714
0.5301 Remote Similarity NPC470886
0.5269 Remote Similarity NPC174607
0.5269 Remote Similarity NPC147847
0.5238 Remote Similarity NPC66855
0.5227 Remote Similarity NPC487915
0.5104 Remote Similarity NPC609979
0.5057 Remote Similarity NPC477220

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC304257 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