Natural Product: NPC193351

Natural Product IDNPC193351
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Xanthinosin
IUPAC Name (3aR,7S,8aS)-7-methyl-3-methylidene-6-(3-oxobutyl)-4,7,8,8a-tetrahydro-3aH-cyclohepta[b]furan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL257513
PubChem CID 44453629
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001543] Sesquiterpene lactones
            • [CHEMONTID:0000502] Xanthanolides

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 AVFIYMSJDDGDBQ-FZZIBODNSA-N
Standard InCHI InChI=1S/C15H20O3/c1-9-8-14-13(11(3)15(17)18-14)7-6-12(9)5-4-10(2)16/h6,9,13-14H,3-5,7-8H2,1-2H3/t9-,13+,14-/m0/s1
SMILES C[C@H]1C[C@H]2[C@H](CC=C1CCC(=O)C)C(=C)C(=O)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   248.14 Volume:   266.708
?
Van der Waals volume.
Dense:   0.93 LogP:   2.739
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.564
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.929
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
TPSA:   43.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.438 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.117 Fsp3:   0.6
MCE-18:   31.417
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.143 Fluc inhibitor:   0.028
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.02
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.966 Promiscuous compounds:   0.235

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.714 MDCK Permeability:   -4.536
Pgp-inhibitor:   0.296 Pgp-substrate:   0.032
PAMPA:   0.166
?
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):   0.003
20% Bioavailability (F20%):   0.143 30% Bioavailability (F30%):   0.49
50% Bioavailability (F50%):   0.86

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.248 MRP1:   0.911
Plasma Protein Binding (PPB):   95.065% Volume Distribution (VD):   0.383
Fu: 4.861%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.019
BSEP inhibitor:   0.921

ADMET: Metabolism

CYP1A2-inhibitor:   0.128 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.583 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.008
CYP3A4-inhibitor:   0.092 CYP3A4-substrate:   0.015
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.604
HLM stability:   0.418
?
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):  6.511 Half-life (T1/2):  1.443

ADMET: Toxicity

hERG Blockers:  0.037 hERG Blockers (10um):  0.239
Human Hepatotoxicity (H-HT):  0.626 Drug-induced Liver Injury (DILI):  0.814
AMES Toxicity:  0.283 Rat Oral Acute Toxicity:  0.169
Maximum Recommended Daily Dose:  0.545 Skin Sensitization:  0.965
Carcinogencity:  0.694 Eye Corrosion:  0.663
Eye Irritation:  0.962 Respiratory Toxicity:  0.394
Drug-induced Neurotoxicity:  0.747 Ototoxicity:  0.466
Hematotoxicity:  0.546 Drug-induced Nephrotoxicity:  0.682
Genotoxicity:  0.282 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.065 Hek293 Cytotoxicity:  0.124
BCF:   0.515
?
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:   3.141
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.499
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.879
?
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
NPO2494 Xanthium strumarium Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[26081757]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota Fruits n.a. n.a. PMID[26110443]
NPO2494 Xanthium strumarium Species Asteraceae Eukaryota n.a. aerial part n.a. PMID[27169184]
NPO2494 Xanthium strumarium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24356 Fructus xanthii sibirici n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2494 Xanthium strumarium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17612 Xanthium sibiricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2494 Xanthium strumarium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17612 Xanthium sibiricum Species Asteraceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT34 Cell line BV-2 Mus musculus IC50 = 11200.0 nM PMID[18276135]
NPT196 Cell line AGS Homo sapiens Activity = 65.0 % PMID[26081757]
NPT196 Cell line AGS Homo sapiens Activity = 25.0 % PMID[26081757]
NPT196 Cell line AGS Homo sapiens Activity = 20.0 % PMID[26081757]
NPT196 Cell line AGS Homo sapiens Activity = 10.0 % PMID[26081757]
NPT196 Cell line AGS Homo sapiens Activity = 100.0 % PMID[26081757]
NPT196 Cell line AGS Homo sapiens Inhibition = 24.0 % PMID[26081757]
NPT196 Cell line AGS Homo sapiens Inhibition = 44.0 % PMID[26081757]
NPT196 Cell line AGS Homo sapiens Inhibition = 32.0 % PMID[26081757]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 5600.0 nM PMID[26110443]
NPT3119 Organism Human coxsackievirus B3 Human coxsackievirus B3 IC50 > 35000.0 nM PMID[26110443]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 35000.0 nM PMID[26110443]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Inhibition = 46.9 % PMID[26110443]





 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 NPC193351 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
1.0 High Similarity NPC226669
1.0 High Similarity NPC138408
0.7273 Intermediate Similarity NPC470244
0.7273 Intermediate Similarity NPC470240
0.7273 Intermediate Similarity NPC470239
0.7273 Intermediate Similarity NPC486582
0.7111 Intermediate Similarity NPC483167
0.6809 Remote Similarity NPC476794
0.6522 Remote Similarity NPC301477
0.6522 Remote Similarity NPC25684
0.6383 Remote Similarity NPC483163
0.6364 Remote Similarity NPC63649
0.6364 Remote Similarity NPC264227
0.6279 Remote Similarity NPC472960
0.625 Remote Similarity NPC483165
0.625 Remote Similarity NPC483164
0.6222 Remote Similarity NPC296522
0.6222 Remote Similarity NPC144511
0.6222 Remote Similarity NPC486580
0.617 Remote Similarity NPC318468
0.617 Remote Similarity NPC281949
0.6 Remote Similarity NPC483166
0.587 Remote Similarity NPC65603
0.5833 Remote Similarity NPC165162

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC193351 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