Natural Product: NPC515470

Natural Product IDNPC515470
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~{S})-3,4-dihydroxy-5-[6-(3-methylbut-2-enylamino)purin-9-yl]tetrahydrofuran-2-yl]methyl dihydrogen phosphate
IUPAC Name [(2~{S},3~{R},4~{S},5~{S})-3,4-dihydroxy-5-[6-(3-methylbut-2-enylamino)purin-9-yl]tetrahydrofuran-2-yl]methyl dihydrogen phosphate
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 DUISZFLWBAPRBR-OXUWNYNTSA-N
Standard InCHI InChI=1S/C15H22N5O7P/c1-8(2)3-4-16-13-10-14(18-6-17-13)20(7-19-10)15-12(22)11(21)9(27-15)5-26-28(23,24)25/h3,6-7,9,11-12,15,21-22H,4-5H2,1-2H3,(H,16,17,18)(H2,23,24,25)/t9-,11-,12-,15-/m0/s1
SMILES CC(C)=CCNC1=NC=NC2=C1N=CN2[C@H]1O[C@@H](COP(=O)(O)O)[C@H](O)[C@@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   415.13 Volume:   365.487
?
Van der Waals volume.
Dense:   1.136 LogP:   0.005
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.172
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.465
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   17.0
TPSA:   172.08
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   13.0

MedChem Properties

QED Drug-Likeness Score:   0.303 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.058 Fsp3:   0.533
MCE-18:   70.304
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.129 Fluc inhibitor:   0.007
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.04
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.053
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.01 Promiscuous compounds:   0.018

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.757 MDCK Permeability:   -5.176
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
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):   0.001
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.053
50% Bioavailability (F50%):   0.558

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.142
Plasma Protein Binding (PPB):   44.216% Volume Distribution (VD):   -0.264
Fu: 57.307%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.135
BSEP inhibitor:   0.82

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.981 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.885
HLM stability:   0.156
?
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):  2.724 Half-life (T1/2):  2.208

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.059
Human Hepatotoxicity (H-HT):  0.258 Drug-induced Liver Injury (DILI):  0.859
AMES Toxicity:  0.413 Rat Oral Acute Toxicity:  0.038
Maximum Recommended Daily Dose:  0.687 Skin Sensitization:  0.996
Carcinogencity:  0.8 Eye Corrosion:  0.001
Eye Irritation:  0.719 Respiratory Toxicity:  0.963
Drug-induced Neurotoxicity:  0.245 Ototoxicity:  0.364
Hematotoxicity:  0.11 Drug-induced Nephrotoxicity:  0.983
Genotoxicity:  0.999 RPMI-8226 Immunitoxicity:  0.1
A549 Cytotoxicity:  0.014 Hek293 Cytotoxicity:  0.094
BCF:   0.129
?
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:   2.634
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.127
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.314
?
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]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[10336650]
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]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[15679315]
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]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[16252923]
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]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[17624889]
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]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[18611049]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[18768384]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[19476340]
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]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[21912858]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[22111577]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. flower n.a. PMID[22166201]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[23370715]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[23790907]
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]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[24948953]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[25457500]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[25564559]
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]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[29154541]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[30384263]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[37631012]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[38354824]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[39199155]
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]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. Database[MetaboLights]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13879 Humulus lupulus Species Cannabaceae 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 NPC515470 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
0.75 Intermediate Similarity NPC605318
0.7429 Intermediate Similarity NPC239737
0.7183 Intermediate Similarity NPC185991
0.7183 Intermediate Similarity NPC321814
0.6282 Remote Similarity NPC130586
0.6216 Remote Similarity NPC261595
0.6125 Remote Similarity NPC174802
0.6049 Remote Similarity NPC606410
0.6027 Remote Similarity NPC136349
0.6027 Remote Similarity NPC219313
0.5949 Remote Similarity NPC324198
0.5949 Remote Similarity NPC195140
0.5949 Remote Similarity NPC326529
0.5949 Remote Similarity NPC319100
0.5783 Remote Similarity NPC323091
0.5595 Remote Similarity NPC316618
0.557 Remote Similarity NPC328479
0.5432 Remote Similarity NPC324033
0.5422 Remote Similarity NPC321458
0.5238 Remote Similarity NPC324484
0.5185 Remote Similarity NPC121222
0.5122 Remote Similarity NPC164952
0.5068 Remote Similarity NPC317821

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC515470 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
0.7183 Intermediate Similarity NPD283 Phase 4
0.6216 Remote Similarity NPD247 Clinical (unspecified phase)
0.6125 Remote Similarity NPD339 Phase 2
0.6027 Remote Similarity NPD548 Clinical (unspecified phase)
0.5696 Remote Similarity NPD242 Phase 4
0.5696 Remote Similarity NPD4171 Clinical (unspecified phase)
0.5556 Remote Similarity NPD338 Approved
0.5122 Remote Similarity NPD1369 Phase 2
0.5122 Remote Similarity NPD1750 Clinical (unspecified phase)
0.5114 Remote Similarity NPD1732 Phase 3
0.5114 Remote Similarity NPD2624 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