Natural Product: NPC171116

Natural Product IDNPC171116
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3'-O-Acetyl-2'-Deoxythymidine
IUPAC Name [(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] acetate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL266234
PubChem CID 464365
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000289] Nucleosides, nucleotides, and analogues
      • [CHEMONTID:0000480] Pyrimidine nucleosides
        • [CHEMONTID:0002180] Pyrimidine 2'-deoxyribonucleosides

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 IRFKBRPHBYCMQU-IVZWLZJFSA-N
Standard InCHI InChI=1S/C12H16N2O6/c1-6-4-14(12(18)13-11(6)17)10-3-8(19-7(2)16)9(5-15)20-10/h4,8-10,15H,3,5H2,1-2H3,(H,13,17,18)/t8-,9+,10+/m0/s1
SMILES OC[C@H]1O[C@H](C[C@@H]1OC(=O)C)n1cc(C)c(nc1=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.1 Volume:   263.184
?
Van der Waals volume.
Dense:   1.079 LogP:   -0.97
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.636
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.689
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   13.0
TPSA:   110.88
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.718 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.817 Fsp3:   0.583
MCE-18:   47.895
?
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:   0.408 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.035
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.015
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.031 Promiscuous compounds:   0.389

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.519 MDCK Permeability:   -5.067
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   0.939
?
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):   0.0
20% Bioavailability (F20%):   0.008 30% Bioavailability (F30%):   0.004
50% Bioavailability (F50%):   0.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   1.0
Plasma Protein Binding (PPB):   10.726% Volume Distribution (VD):   -0.072
Fu: 95.272%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.376
OATP1B3 inhibitor:   0.081 BCRP inhibitor:   0.0
BSEP inhibitor:   0.219

ADMET: Metabolism

CYP1A2-inhibitor:   0.402 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.893 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.741 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.99 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.106 CYP2C8-inhibitor:   0.013
HLM stability:   0.584
?
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):  2.92 Half-life (T1/2):  1.305

ADMET: Toxicity

hERG Blockers:  0.016 hERG Blockers (10um):  0.061
Human Hepatotoxicity (H-HT):  0.828 Drug-induced Liver Injury (DILI):  0.983
AMES Toxicity:  0.849 Rat Oral Acute Toxicity:  0.304
Maximum Recommended Daily Dose:  0.248 Skin Sensitization:  0.988
Carcinogencity:  0.646 Eye Corrosion:  0.003
Eye Irritation:  0.38 Respiratory Toxicity:  0.185
Drug-induced Neurotoxicity:  0.704 Ototoxicity:  0.673
Hematotoxicity:  0.536 Drug-induced Nephrotoxicity:  0.64
Genotoxicity:  0.992 RPMI-8226 Immunitoxicity:  0.082
A549 Cytotoxicity:  0.116 Hek293 Cytotoxicity:  0.117
BCF:   0.146
?
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:   2.495
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.009
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.16
?
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
NPO19812 Pimelea simplex Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[21049973]
NPO12352 Magnolia baillonii Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[3437284]
NPO10921 Cercospora ligustri Species Mycosphaerellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12352 Magnolia baillonii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19812 Pimelea simplex Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19146 Cosmos bipinnatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19551 Cocculus pendulus Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17984 Aplysia angasi Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13189 Carex folliculata Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18651 Piper lolot Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16902 Dendroctonus brevicomis Species Curculionidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18223 Dictyostelium brefeldianum Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11741 Glycosmis parviflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19681 Hypoxis filiformis Species Hypoxidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19611 Ipomoea tuberosa Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18898 Madhuca utilis Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14131 Phyllanthus maderaspatensis Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19551 Cocculus pendulus Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19812 Pimelea simplex Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19551 Cocculus pendulus Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19812 Pimelea simplex Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19812 Pimelea simplex Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18223 Dictyostelium brefeldianum Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19551 Cocculus pendulus Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19681 Hypoxis filiformis Species Hypoxidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18898 Madhuca utilis Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17984 Aplysia angasi Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10921 Cercospora ligustri Species Mycosphaerellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12352 Magnolia baillonii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19611 Ipomoea tuberosa Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14131 Phyllanthus maderaspatensis Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13189 Carex folliculata Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16902 Dendroctonus brevicomis Species Curculionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11741 Glycosmis parviflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18651 Piper lolot Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19146 Cosmos bipinnatus 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
NPT907 Individual protein Ribonuclease pancreatic Homo sapiens Inhibition = 38.0 % PMID[18226913]
NPT907 Individual protein Ribonuclease pancreatic Homo sapiens IC50 = 197000.0 nM PMID[18226913]
NPT907 Individual protein Ribonuclease pancreatic Homo sapiens Ki = 42000.0 nM PMID[18226913]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1452 Cell line C8166 Homo sapiens ED50 > 200.0 uM DOI[10.1016/S0960-894X(00)80316-9]
NPT2 Others Unspecified n.a. Ki = 58000.0 nM PMID[214555]

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 NPC171116 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
0.6724 Remote Similarity NPC478793
0.625 Remote Similarity NPC71339
0.5517 Remote Similarity NPC163352
0.5517 Remote Similarity NPC210456
0.5294 Remote Similarity NPC482623
0.5286 Remote Similarity NPC318166
0.5231 Remote Similarity NPC327344

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC171116 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
0.6724 Remote Similarity NPD251 Phase 4
0.625 Remote Similarity NPD280 Phase 4
0.614 Remote Similarity NPD238 Clinical (unspecified phase)
0.614 Remote Similarity NPD239 Phase 2
0.5517 Remote Similarity NPD205 Phase 4
0.5246 Remote Similarity NPD240 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