Natural Product: NPC514003

Natural Product IDNPC514003
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 nucleoside
IUPAC Name [(2~{S},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl]methyl-dimethyl-oxido-arsonium
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 XYMACCGOWRMDES-WOUKDFQISA-N
Standard InCHI InChI=1S/C12H18AsN5O4/c1-13(2,21)3-6-8(19)9(20)12(22-6)18-5-17-7-10(14)15-4-16-11(7)18/h4-6,8-9,12,19-20H,3H2,1-2H3,(H2,14,15,16)/t6-,8-,9-,12-/m1/s1
SMILES C[As+](C)([O-])C[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:   371.06 Volume:   26522114.216
?
Van der Waals volume.
Dense:   0.0 LogP:   -1.13
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.802
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.875
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   15.0
TPSA:   142.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.559 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.512 Fsp3:   0.583
MCE-18:   68.421
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.05 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.164
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.003
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.029 Promiscuous compounds:   0.087

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.82 MDCK Permeability:   -4.924
Pgp-inhibitor:   0.0 Pgp-substrate:   0.95
PAMPA:   0.997
?
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):   0.653
20% Bioavailability (F20%):   0.496 30% Bioavailability (F30%):   0.995
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.058 MRP1:   0.305
Plasma Protein Binding (PPB):   22.824% Volume Distribution (VD):   -0.057
Fu: 76.712%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.596
OATP1B3 inhibitor:   0.872 BCRP inhibitor:   0.014
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.013 CYP2D6-substrate:   0.113
CYP3A4-inhibitor:   0.018 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.004
HLM stability:   0.002
?
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):  5.319 Half-life (T1/2):  2.717

ADMET: Toxicity

hERG Blockers:  0.034 hERG Blockers (10um):  0.038
Human Hepatotoxicity (H-HT):  0.796 Drug-induced Liver Injury (DILI):  0.907
AMES Toxicity:  0.949 Rat Oral Acute Toxicity:  0.954
Maximum Recommended Daily Dose:  0.994 Skin Sensitization:  1.0
Carcinogencity:  0.102 Eye Corrosion:  0.208
Eye Irritation:  0.994 Respiratory Toxicity:  1.0
Drug-induced Neurotoxicity:  0.185 Ototoxicity:  0.012
Hematotoxicity:  0.139 Drug-induced Nephrotoxicity:  0.983
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.162
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.003
BCF:   0.125
?
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:   2.531
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.043
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.111
?
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
NPO14633 Tridacna maxima Species Tridacnidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14633 Tridacna maxima Species Tridacnidae 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 NPC514003 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
0.7778 Intermediate Similarity NPC317821
0.75 Intermediate Similarity NPC156461
0.75 Intermediate Similarity NPC107374
0.75 Intermediate Similarity NPC600382
0.75 Intermediate Similarity NPC612067
0.6885 Remote Similarity NPC136349
0.6885 Remote Similarity NPC219313
0.678 Remote Similarity NPC229974
0.6571 Remote Similarity NPC325906
0.6515 Remote Similarity NPC328479
0.6364 Remote Similarity NPC185991
0.6364 Remote Similarity NPC321814
0.6338 Remote Similarity NPC606116
0.6286 Remote Similarity NPC324484
0.6232 Remote Similarity NPC324198
0.6232 Remote Similarity NPC326529
0.6232 Remote Similarity NPC319100
0.5972 Remote Similarity NPC174802
0.5968 Remote Similarity NPC209525
0.5968 Remote Similarity NPC161659
0.5915 Remote Similarity NPC130586
0.589 Remote Similarity NPC606410
0.5811 Remote Similarity NPC323091
0.5625 Remote Similarity NPC609472
0.56 Remote Similarity NPC316618
0.5588 Remote Similarity NPC85689
0.5556 Remote Similarity NPC33996
0.5538 Remote Similarity NPC309832
0.5467 Remote Similarity NPC481375
0.5455 Remote Similarity NPC484199
0.5441 Remote Similarity NPC605318
0.5429 Remote Similarity NPC239737
0.5385 Remote Similarity NPC164665
0.5385 Remote Similarity NPC484196
0.5278 Remote Similarity NPC164952
0.525 Remote Similarity NPC478860
0.5231 Remote Similarity NPC609036
0.5205 Remote Similarity NPC302778
0.5205 Remote Similarity NPC329404
0.5205 Remote Similarity NPC212551
0.5143 Remote Similarity NPC211025
0.5139 Remote Similarity NPC121222
0.5135 Remote Similarity NPC195140
0.5075 Remote Similarity NPC269827
0.5075 Remote Similarity NPC189068

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC514003 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
0.75 Intermediate Similarity NPD249 Phase 4
0.75 Intermediate Similarity NPD250 Phase 4
0.6885 Remote Similarity NPD548 Clinical (unspecified phase)
0.6667 Remote Similarity NPD4171 Clinical (unspecified phase)
0.6571 Remote Similarity NPD1777 Phase 4
0.6471 Remote Similarity NPD338 Approved
0.6389 Remote Similarity NPD1776 Approved
0.6364 Remote Similarity NPD283 Phase 4
0.5972 Remote Similarity NPD339 Phase 2
0.5538 Remote Similarity NPD193 Phase 2
0.5278 Remote Similarity NPD1369 Phase 2
0.5278 Remote Similarity NPD1750 Clinical (unspecified phase)
0.5152 Remote Similarity NPD186 Phase 1
0.5075 Remote Similarity NPD195 Approved

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