Natural Product: NPC328479

Natural Product IDNPC328479
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5'-(Aminopropylthio)-5'-Deoxy-Adenosine
IUPAC Name (2S,3S,4R,5R)-2-(3-aminopropylsulfanylmethyl)-5-(6-aminopurin-9-yl)oxolane-3,4-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL538693
PubChem CID 171251
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000289] Nucleosides, nucleotides, and analogues
      • [CHEMONTID:0004502] 5'-deoxyribonucleosides
        • [CHEMONTID:0004503] 5'-deoxy-5'-thionucleosides

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 FUSRAALGPJJIRO-QYVSTXNMSA-N
Standard InCHI InChI=1S/C13H20N6O3S/c14-2-1-3-23-4-7-9(20)10(21)13(22-7)19-6-18-8-11(15)16-5-17-12(8)19/h5-7,9-10,13,20-21H,1-4,14H2,(H2,15,16,17)/t7-,9-,10-,13-/m1/s1
SMILES C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)CSCCCN)O)O)N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.13 Volume:   308.049
?
Van der Waals volume.
Dense:   1.104 LogP:   -0.929
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.368
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.535
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   15.0
TPSA:   145.33
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.492 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.849 Fsp3:   0.615
MCE-18:   57.476
?
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:   0.182 Fluc inhibitor:   0.013
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.156
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.224
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.144 Promiscuous compounds:   0.016

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.872 MDCK Permeability:   -5.612
Pgp-inhibitor:   0.0 Pgp-substrate:   0.607
PAMPA:   0.995
?
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):   0.883
20% Bioavailability (F20%):   0.018 30% Bioavailability (F30%):   0.316
50% Bioavailability (F50%):   0.275

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.279 MRP1:   0.386
Plasma Protein Binding (PPB):   20.508% Volume Distribution (VD):   -0.084
Fu: 79.676%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.409
OATP1B3 inhibitor:   0.887 BCRP inhibitor:   0.001
BSEP inhibitor:   0.004

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:   0.091 CYP2D6-substrate:   0.006
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.0
?
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):  7.483 Half-life (T1/2):  1.429

ADMET: Toxicity

hERG Blockers:  0.21 hERG Blockers (10um):  0.503
Human Hepatotoxicity (H-HT):  0.727 Drug-induced Liver Injury (DILI):  0.631
AMES Toxicity:  0.793 Rat Oral Acute Toxicity:  0.58
Maximum Recommended Daily Dose:  0.489 Skin Sensitization:  0.9
Carcinogencity:  0.677 Eye Corrosion:  0.0
Eye Irritation:  0.019 Respiratory Toxicity:  0.434
Drug-induced Neurotoxicity:  0.947 Ototoxicity:  0.954
Hematotoxicity:  0.483 Drug-induced Nephrotoxicity:  0.808
Genotoxicity:  0.967 RPMI-8226 Immunitoxicity:  0.115
A549 Cytotoxicity:  0.038 Hek293 Cytotoxicity:  0.428
BCF:   0.095
?
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:   2.672
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.158
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.3
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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
NPO8923 Ariopsis felis Species Ariidae Eukaryota n.a. n.a. n.a. PMID[942371]
NPO8923 Ariopsis felis Species Ariidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8923 Ariopsis felis Species Ariidae 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
NPT2752 Individual protein DNA (cytosine-5)-methyltransferase 1 Homo sapiens IC50 > 45000.0 nM PMID[19364644]
NPT6098 Individual protein Histone-lysine N-methyltransferase, H3 lysine-79 specific Homo sapiens Ki = 100000.0 nM PMID[23879463]
NPT3537 Individual protein DNA (cytosine-5)-methyltransferase 3B Homo sapiens IC50 = 17000.0 nM PMID[19364644]
NPT29574 Single protein tRNA (cytosine(38)-C(5))-methyltransferase Homo sapiens Activity n.a. n.a. n.a. PMID[35849534]
NPT29574 Single protein tRNA (cytosine(38)-C(5))-methyltransferase Homo sapiens Inhibition n.a. n.a. % PMID[35849534]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei IC50 > 100000.0 nM PMID[17954686]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei IC50 = 72500.0 nM PMID[17954686]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei IC50 = 15750.0 nM PMID[17954686]
NPT2 Others Unspecified n.a. Activity = 46.0 % PMID[17954686]
NPT2 Others Unspecified n.a. Activity = 60.0 % PMID[17954686]

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 NPC328479 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
0.8 Intermediate Similarity NPC136349
0.8 Intermediate Similarity NPC219313
0.75 Intermediate Similarity NPC324484
0.7385 Intermediate Similarity NPC185991
0.7385 Intermediate Similarity NPC321814
0.6957 Remote Similarity NPC324198
0.6957 Remote Similarity NPC326529
0.6957 Remote Similarity NPC319100
0.6885 Remote Similarity NPC156461
0.6885 Remote Similarity NPC107374
0.6885 Remote Similarity NPC600382
0.6885 Remote Similarity NPC612067
0.6857 Remote Similarity NPC130586
0.6833 Remote Similarity NPC317821
0.6667 Remote Similarity NPC174802
0.6575 Remote Similarity NPC606410
0.6486 Remote Similarity NPC316618
0.6486 Remote Similarity NPC323091
0.6316 Remote Similarity NPC484199
0.6234 Remote Similarity NPC484196
0.6027 Remote Similarity NPC195140
0.6 Remote Similarity NPC229974
0.5758 Remote Similarity NPC209525
0.5758 Remote Similarity NPC161659
0.5714 Remote Similarity NPC325906
0.5714 Remote Similarity NPC606116
0.5672 Remote Similarity NPC609472
0.5616 Remote Similarity NPC121222
0.5333 Remote Similarity NPC472816
0.5333 Remote Similarity NPC164952
0.5333 Remote Similarity NPC600171
0.5319 Remote Similarity NPC90902
0.5316 Remote Similarity NPC481375
0.5263 Remote Similarity NPC302778
0.5263 Remote Similarity NPC329404
0.5263 Remote Similarity NPC212551
0.5217 Remote Similarity NPC21461
0.5205 Remote Similarity NPC261595
0.5205 Remote Similarity NPC85689
0.5147 Remote Similarity NPC33996
0.5143 Remote Similarity NPC309832
0.5125 Remote Similarity NPC161224
0.5068 Remote Similarity NPC605318
0.5067 Remote Similarity NPC239737

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC328479 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
0.8 Intermediate Similarity NPD548 Clinical (unspecified phase)
0.7385 Intermediate Similarity NPD283 Phase 4
0.7164 Intermediate Similarity NPD4171 Clinical (unspecified phase)
0.6957 Remote Similarity NPD338 Approved
0.6885 Remote Similarity NPD249 Phase 4
0.6885 Remote Similarity NPD250 Phase 4
0.6667 Remote Similarity NPD339 Phase 2
0.5714 Remote Similarity NPD1777 Phase 4
0.557 Remote Similarity NPD1776 Approved
0.5541 Remote Similarity NPD1369 Phase 2
0.5333 Remote Similarity NPD242 Phase 4
0.5319 Remote Similarity NPD4716 Approved
0.5205 Remote Similarity NPD247 Clinical (unspecified phase)
0.5143 Remote Similarity NPD193 Phase 2
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