Natural Product: NPC189068

Natural Product IDNPC189068
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Spongosine
IUPAC Name (2R,3R,4S,5R)-2-(6-amino-2-methoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
Synonyms Spongosine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL470888
PubChem CID 9796227
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000289] Nucleosides, nucleotides, and analogues
      • [CHEMONTID:0000479] Purine nucleosides

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 AJACDNCVEGIBNA-KQYNXXCUSA-N
Standard InCHI InChI=1S/C11H15N5O5/c1-20-11-14-8(12)5-9(15-11)16(3-13-5)10-7(19)6(18)4(2-17)21-10/h3-4,6-7,10,17-19H,2H2,1H3,(H2,12,14,15)/t4-,6-,7-,10-/m1/s1
SMILES OC[C@H]1O[C@H]([C@@H]([C@@H]1O)O)n1cnc2c1nc(OC)nc2N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   297.11 Volume:   261.532
?
Van der Waals volume.
Dense:   1.136 LogP:   -0.779
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.334
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.407
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   15.0
TPSA:   148.77
?
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:   0.506 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.661 Fsp3:   0.545
MCE-18:   62.471
?
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:   0.199 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.356
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.03
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.027 Promiscuous compounds:   0.176

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.716 MDCK Permeability:   -5.063
Pgp-inhibitor:   0.0 Pgp-substrate:   0.328
PAMPA:   0.769
?
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):   0.404
20% Bioavailability (F20%):   0.087 30% Bioavailability (F30%):   0.847
50% Bioavailability (F50%):   0.69

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.429 MRP1:   0.511
Plasma Protein Binding (PPB):   57.168% Volume Distribution (VD):   0.679
Fu: 42.619%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.016
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.025 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.005
CYP3A4-inhibitor:   0.081 CYP3A4-substrate:   0.015
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.046
HLM stability:   0.015
?
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):  8.707 Half-life (T1/2):  2.043

ADMET: Toxicity

hERG Blockers:  0.043 hERG Blockers (10um):  0.2
Human Hepatotoxicity (H-HT):  0.869 Drug-induced Liver Injury (DILI):  0.94
AMES Toxicity:  0.87 Rat Oral Acute Toxicity:  0.106
Maximum Recommended Daily Dose:  0.191 Skin Sensitization:  0.89
Carcinogencity:  0.662 Eye Corrosion:  0.0
Eye Irritation:  0.251 Respiratory Toxicity:  0.268
Drug-induced Neurotoxicity:  0.828 Ototoxicity:  0.909
Hematotoxicity:  0.734 Drug-induced Nephrotoxicity:  0.809
Genotoxicity:  0.976 RPMI-8226 Immunitoxicity:  0.133
A549 Cytotoxicity:  0.196 Hek293 Cytotoxicity:  0.278
BCF:   0.005
?
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:   2.075
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.642
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.816
?
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
NPO30675 Vibrio harveyi Species Vibrionaceae Bacteria n.a. n.a. n.a. PMID[23305926]
NPO30675 Vibrio harveyi Species Vibrionaceae Bacteria n.a. n.a. n.a. PMID[25668560]
NPO30675 Vibrio harveyi Species Vibrionaceae Bacteria n.a. n.a. n.a. PMID[311472]

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
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 60.0 % PMID[17194596]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus ED50 = 15.3 mg.kg-1 PMID[26200131]
NPT32 Organism Mus musculus Mus musculus ED50 = 12.5 mg.kg-1 PMID[25781655]
NPT29 Organism Rattus norvegicus Rattus norvegicus BP = -41.0 % PMID[7328598]
NPT29 Organism Rattus norvegicus Rattus norvegicus HR = -25.0 % PMID[7328598]
NPT29 Organism Rattus norvegicus Rattus norvegicus Inhibition = 25.0 % PMID[26200131]
NPT29 Organism Rattus norvegicus Rattus norvegicus Inhibition = 56.0 % PMID[26291474]
NPT29 Organism Rattus norvegicus Rattus norvegicus Inhibition = 57.0 % PMID[26200131]





 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 NPC189068 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
0.6667 Remote Similarity NPC156461
0.6667 Remote Similarity NPC107374
0.6667 Remote Similarity NPC600382
0.6667 Remote Similarity NPC612067
0.6552 Remote Similarity NPC609036
0.6441 Remote Similarity NPC164665
0.6333 Remote Similarity NPC269827
0.5556 Remote Similarity NPC608983
0.55 Remote Similarity NPC317821
0.5385 Remote Similarity NPC136349
0.5385 Remote Similarity NPC219313
0.5161 Remote Similarity NPC485738
0.5161 Remote Similarity NPC54320
0.5156 Remote Similarity NPC321052
0.5079 Remote Similarity NPC311197

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC189068 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
0.6667 Remote Similarity NPD249 Phase 4
0.6667 Remote Similarity NPD250 Phase 4
0.6479 Remote Similarity NPD2902 Phase 2
0.6479 Remote Similarity NPD2903 Clinical (unspecified phase)
0.6333 Remote Similarity NPD195 Approved
0.5385 Remote Similarity NPD548 Clinical (unspecified phase)
0.5278 Remote Similarity NPD3107 Discontinued
0.5161 Remote Similarity NPD219 Phase 4
0.5161 Remote Similarity NPD220 Clinical (unspecified phase)
0.5135 Remote Similarity NPD2647 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