Natural Product: NPC525749

Natural Product IDNPC525749
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Xylo-mta
IUPAC Name (2~{R},3~{R},4~{R},5~{S})-2-(6-aminopurin-9-yl)-5-(methylsulfanylmethyl)tetrahydrofuran-3,4-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 WUUGFSXJNOTRMR-GZCUOZMLSA-N
Standard InCHI InChI=1S/C11H15N5O3S/c1-20-2-5-7(17)8(18)11(19-5)16-4-15-6-9(12)13-3-14-10(6)16/h3-5,7-8,11,17-18H,2H2,1H3,(H2,12,13,14)/t5-,7+,8-,11-/m1/s1
SMILES CSC[C@H]1O[C@@H](N2C=NC3=C(N)N=CN=C32)[C@H](O)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   297.09 Volume:   262.461
?
Van der Waals volume.
Dense:   1.132 LogP:   0.04
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.372
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.797
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   15.0
TPSA:   119.31
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.686 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.776 Fsp3:   0.545
MCE-18:   59.0
?
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:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.236 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.169
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.073
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.474 Promiscuous compounds:   0.127

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.816 MDCK Permeability:   -5.021
Pgp-inhibitor:   0.001 Pgp-substrate:   0.908
PAMPA:   0.983
?
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):   0.029
20% Bioavailability (F20%):   0.017 30% Bioavailability (F30%):   0.07
50% Bioavailability (F50%):   0.401

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.018 MRP1:   0.243
Plasma Protein Binding (PPB):   33.654% Volume Distribution (VD):   -0.01
Fu: 64.688%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.637
OATP1B3 inhibitor:   0.792 BCRP inhibitor:   0.002
BSEP inhibitor:   0.088

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.092
CYP3A4-inhibitor:   0.008 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.094
HLM stability:   0.193
?
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):  6.993 Half-life (T1/2):  1.982

ADMET: Toxicity

hERG Blockers:  0.048 hERG Blockers (10um):  0.299
Human Hepatotoxicity (H-HT):  0.686 Drug-induced Liver Injury (DILI):  0.946
AMES Toxicity:  0.919 Rat Oral Acute Toxicity:  0.388
Maximum Recommended Daily Dose:  0.15 Skin Sensitization:  0.784
Carcinogencity:  0.526 Eye Corrosion:  0.0
Eye Irritation:  0.488 Respiratory Toxicity:  0.342
Drug-induced Neurotoxicity:  0.8 Ototoxicity:  0.834
Hematotoxicity:  0.767 Drug-induced Nephrotoxicity:  0.874
Genotoxicity:  0.997 RPMI-8226 Immunitoxicity:  0.128
A549 Cytotoxicity:  0.078 Hek293 Cytotoxicity:  0.264
BCF:   0.142
?
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:   2.311
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.052
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.055
?
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
NPO23325 Doris verrucosa Species Dorididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23325 Doris verrucosa Species Dorididae 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

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 NPC525749 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 NPC136349
1.0 High Similarity NPC219313
0.8136 Intermediate Similarity NPC185991
0.8136 Intermediate Similarity NPC321814
0.8 Intermediate Similarity NPC328479
0.7636 Intermediate Similarity NPC156461
0.7636 Intermediate Similarity NPC107374
0.7636 Intermediate Similarity NPC600382
0.7636 Intermediate Similarity NPC612067
0.7619 Intermediate Similarity NPC324198
0.7619 Intermediate Similarity NPC326529
0.7619 Intermediate Similarity NPC319100
0.7593 Intermediate Similarity NPC317821
0.75 Intermediate Similarity NPC130586
0.7385 Intermediate Similarity NPC324484
0.7273 Intermediate Similarity NPC174802
0.7164 Intermediate Similarity NPC606410
0.7077 Intermediate Similarity NPC195140
0.7059 Intermediate Similarity NPC316618
0.7059 Intermediate Similarity NPC323091
0.6857 Remote Similarity NPC484199
0.6761 Remote Similarity NPC484196
0.6333 Remote Similarity NPC229974
0.5873 Remote Similarity NPC309832
0.5806 Remote Similarity NPC209525
0.5806 Remote Similarity NPC161659
0.5797 Remote Similarity NPC472816
0.5797 Remote Similarity NPC164952
0.5797 Remote Similarity NPC600171
0.5753 Remote Similarity NPC325906
0.5753 Remote Similarity NPC606116
0.5714 Remote Similarity NPC302778
0.5714 Remote Similarity NPC329404
0.5714 Remote Similarity NPC212551
0.5714 Remote Similarity NPC609472
0.5672 Remote Similarity NPC85689
0.5652 Remote Similarity NPC121222
0.5645 Remote Similarity NPC33996
0.5581 Remote Similarity NPC21461
0.5522 Remote Similarity NPC605318
0.5507 Remote Similarity NPC239737
0.5441 Remote Similarity NPC261595
0.5385 Remote Similarity NPC269827
0.5385 Remote Similarity NPC189068
0.5333 Remote Similarity NPC481375
0.5333 Remote Similarity NPC90902
0.5312 Remote Similarity NPC609036
0.5231 Remote Similarity NPC164665
0.5217 Remote Similarity NPC211025
0.5161 Remote Similarity NPC611055
0.5132 Remote Similarity NPC161224
0.5128 Remote Similarity NPC611003
0.5077 Remote Similarity NPC604998
0.5068 Remote Similarity NPC324033
0.5067 Remote Similarity NPC321458
0.5067 Remote Similarity NPC250178

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC525749 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
1.0 High Similarity NPD548 Clinical (unspecified phase)
0.8136 Intermediate Similarity NPD283 Phase 4
0.7869 Intermediate Similarity NPD4171 Clinical (unspecified phase)
0.7636 Intermediate Similarity NPD249 Phase 4
0.7636 Intermediate Similarity NPD250 Phase 4
0.7619 Intermediate Similarity NPD338 Approved
0.7273 Intermediate Similarity NPD339 Phase 2
0.5797 Remote Similarity NPD242 Phase 4
0.5753 Remote Similarity NPD1777 Phase 4
0.56 Remote Similarity NPD1776 Approved
0.5571 Remote Similarity NPD1369 Phase 2
0.5526 Remote Similarity NPD1732 Phase 3
0.5441 Remote Similarity NPD247 Clinical (unspecified phase)
0.5385 Remote Similarity NPD193 Phase 2
0.5385 Remote Similarity NPD195 Approved
0.5352 Remote Similarity NPD1750 Clinical (unspecified phase)
0.5333 Remote Similarity NPD4716 Approved
0.5231 Remote Similarity NPD186 Phase 1
0.5135 Remote Similarity NPD2965 Phase 2

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