Natural Product: NPC552222

Natural Product IDNPC552222
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{S},3~{R},4~{S},5~{R})-2-(hydroxymethyl)-5-[6-[[(3~{S})-4-hydroxy-3-methyl-butyl]amino]purin-9-yl]tetrahydrofuran-3,4-diol
IUPAC Name (2~{S},3~{R},4~{S},5~{R})-2-(hydroxymethyl)-5-[6-[[(3~{S})-4-hydroxy-3-methyl-butyl]amino]purin-9-yl]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 DBVVQDGIJAUEAZ-LIOLZPPRSA-N
Standard InCHI InChI=1S/C15H23N5O5/c1-8(4-21)2-3-16-13-10-14(18-6-17-13)20(7-19-10)15-12(24)11(23)9(5-22)25-15/h6-9,11-12,15,21-24H,2-5H2,1H3,(H,16,17,18)/t8-,9-,11-,12-,15+/m0/s1
SMILES C[C@H](CO)CCNC1=NC=NC2=C1N=CN2[C@@H]1O[C@@H](CO)[C@H](O)[C@@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   353.17 Volume:   330.716
?
Van der Waals volume.
Dense:   1.068 LogP:   0.019
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.538
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.673
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   15.0
TPSA:   145.78
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.417 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.88 Fsp3:   0.667
MCE-18:   59.76
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.245 Fluc inhibitor:   0.044
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.033
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.093
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.013 Promiscuous compounds:   0.056

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.937 MDCK Permeability:   -5.21
Pgp-inhibitor:   0.0 Pgp-substrate:   0.732
PAMPA:   0.999
?
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):   0.633
20% Bioavailability (F20%):   0.729 30% Bioavailability (F30%):   0.882
50% Bioavailability (F50%):   0.964

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.104 MRP1:   0.707
Plasma Protein Binding (PPB):   40.623% Volume Distribution (VD):   -0.136
Fu: 60.282%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.822
OATP1B3 inhibitor:   0.723 BCRP inhibitor:   0.038
BSEP inhibitor:   0.008

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.626 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.021 CYP2D6-substrate:   0.076
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.357
HLM stability:   0.146
?
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):  8.83 Half-life (T1/2):  1.605

ADMET: Toxicity

hERG Blockers:  0.022 hERG Blockers (10um):  0.083
Human Hepatotoxicity (H-HT):  0.832 Drug-induced Liver Injury (DILI):  0.959
AMES Toxicity:  0.957 Rat Oral Acute Toxicity:  0.205
Maximum Recommended Daily Dose:  0.043 Skin Sensitization:  1.0
Carcinogencity:  0.603 Eye Corrosion:  0.0
Eye Irritation:  0.368 Respiratory Toxicity:  0.419
Drug-induced Neurotoxicity:  0.827 Ototoxicity:  0.9
Hematotoxicity:  0.915 Drug-induced Nephrotoxicity:  0.952
Genotoxicity:  0.949 RPMI-8226 Immunitoxicity:  0.254
A549 Cytotoxicity:  0.975 Hek293 Cytotoxicity:  0.493
BCF:   0.154
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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:   2.515
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.119
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.082
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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
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0014-5793(03)00033-4]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/ac991142i]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1034/j.1399-3054.2003.00030.x]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1046/j.1365-3040.2001.00686.x]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.274.1.397]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M302362200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M314195200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M411109200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1104/pp.103.022368]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[10952545]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. leaf n.a. PMID[10952545]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[11005203]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[12637544]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[12805618]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[14745019]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15280363]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15820655]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15834012]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota aerial parts n.a. n.a. PMID[15844959]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[1684022]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[17611796]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18057039]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18235971]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18318836]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. leaf n.a. PMID[19521717]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21193570]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21194489]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21395888]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21800258]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[23370715]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[23950498]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[24163311]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24285094]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[25457500]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[27363486]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[27432888]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[8278506]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. Database[MetaboLights]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO19866 Arabidopsis thaliana Species Brassicaceae 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 NPC552222 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
0.7385 Intermediate Similarity NPC239737
0.6613 Remote Similarity NPC156461
0.6613 Remote Similarity NPC107374
0.6613 Remote Similarity NPC600382
0.6613 Remote Similarity NPC612067
0.6418 Remote Similarity NPC605318
0.6301 Remote Similarity NPC250178
0.5781 Remote Similarity NPC317821
0.56 Remote Similarity NPC195140
0.5429 Remote Similarity NPC136349
0.5429 Remote Similarity NPC219313
0.5294 Remote Similarity NPC229974
0.5224 Remote Similarity NPC485738
0.5224 Remote Similarity NPC54320
0.52 Remote Similarity NPC328479
0.5125 Remote Similarity NPC325906
0.5075 Remote Similarity NPC207633
0.5072 Remote Similarity NPC609036

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC552222 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
0.6912 Remote Similarity NPD1750 Clinical (unspecified phase)
0.6667 Remote Similarity NPD1369 Phase 2
0.6613 Remote Similarity NPD249 Phase 4
0.6613 Remote Similarity NPD250 Phase 4
0.6389 Remote Similarity NPD2965 Phase 2
0.5429 Remote Similarity NPD548 Clinical (unspecified phase)
0.5309 Remote Similarity NPD2624 Phase 2
0.5224 Remote Similarity NPD219 Phase 4
0.5224 Remote Similarity NPD220 Clinical (unspecified phase)
0.5185 Remote Similarity NPD1776 Approved
0.5125 Remote Similarity NPD1777 Phase 4
0.5122 Remote Similarity NPD1732 Phase 3

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