Natural Product: NPC512972

Natural Product IDNPC512972
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},6~{R})-2-(hydroxymethyl)-6-(3-nitropropoxy)tetrahydropyran-3,4,5-triol
IUPAC Name (2~{S},3~{R},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-6-(3-nitropropoxy)tetrahydropyran-3,4,5-triol
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 JDJSHLXEHWCLEP-OAHBRNHXSA-N
Standard InCHI InChI=1S/C9H17NO8/c11-4-5-6(12)7(13)8(14)9(18-5)17-3-1-2-10(15)16/h5-9,11-14H,1-4H2/t5-,6-,7-,8+,9+/m0/s1
SMILES O=[N+]([O-])CCCO[C@@H]1O[C@@H](CO)[C@H](O)[C@H](O)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   267.1 Volume:   234.346
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Van der Waals volume.
Dense:   1.14 LogP:   -1.159
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.874
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.577
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   7.0
TPSA:   142.52
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Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   1.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.234 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.93 Fsp3:   1.0
MCE-18:   23.0
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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:   0.07 Fluc inhibitor:   0.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.252
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.246 Promiscuous compounds:   0.002

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.285 MDCK Permeability:   -5.13
Pgp-inhibitor:   0.0 Pgp-substrate:   0.122
PAMPA:   0.987
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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):   0.329
20% Bioavailability (F20%):   0.111 30% Bioavailability (F30%):   0.54
50% Bioavailability (F50%):   0.661

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.468 MRP1:   0.948
Plasma Protein Binding (PPB):   23.403% Volume Distribution (VD):   -0.583
Fu: 79.764%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.745
OATP1B3 inhibitor:   0.976 BCRP inhibitor:   0.155
BSEP inhibitor:   0.009

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.01
CYP2C19-inhibitor:   0.158 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.015
CYP3A4-inhibitor:   0.155 CYP3A4-substrate:   0.515
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.254
HLM stability:   0.235
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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):  3.171 Half-life (T1/2):  1.716

ADMET: Toxicity

hERG Blockers:  0.015 hERG Blockers (10um):  0.151
Human Hepatotoxicity (H-HT):  0.193 Drug-induced Liver Injury (DILI):  0.511
AMES Toxicity:  0.922 Rat Oral Acute Toxicity:  0.18
Maximum Recommended Daily Dose:  0.02 Skin Sensitization:  1.0
Carcinogencity:  0.179 Eye Corrosion:  0.033
Eye Irritation:  0.914 Respiratory Toxicity:  0.125
Drug-induced Neurotoxicity:  0.005 Ototoxicity:  0.468
Hematotoxicity:  0.452 Drug-induced Nephrotoxicity:  0.253
Genotoxicity:  0.99 RPMI-8226 Immunitoxicity:  0.093
A549 Cytotoxicity:  0.021 Hek293 Cytotoxicity:  0.231
BCF:   0.219
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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:   1.954
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.312
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.713
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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
NPO17989 Astragalus falcatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO63685 Astragalus tetraplerus Genus Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56273 Astragalus miser var. oblongifolius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26593 Astragalus canadensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO728 Astragalus atropubescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42253 Astragalus siliquosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO63228 Astragalus toanus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO54822 Astragalus tetrapterus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO58460 Astragalus galegiformis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1 Astragalus flexuosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO45351 Astragalus emoryanus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO50227 Astragalus diversifolius Genus Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO45160 Astragalus convallarius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24077 Astragalus pterocarpus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO728 Astragalus atropubescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1 Astragalus flexuosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17989 Astragalus falcatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24077 Astragalus pterocarpus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO728 Astragalus atropubescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24077 Astragalus pterocarpus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17989 Astragalus falcatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1 Astragalus flexuosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24077 Astragalus pterocarpus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO728 Astragalus atropubescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26593 Astragalus canadensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17989 Astragalus falcatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1 Astragalus flexuosus Species Fabaceae 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 NPC512972 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
0.619 Remote Similarity NPC233726
0.5909 Remote Similarity NPC155457
0.575 Remote Similarity NPC124963
0.5652 Remote Similarity NPC13143
0.5652 Remote Similarity NPC294813
0.5652 Remote Similarity NPC606861
0.5652 Remote Similarity NPC607126
0.561 Remote Similarity NPC326533
0.5294 Remote Similarity NPC277570
0.5098 Remote Similarity NPC147292

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC512972 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
0.5455 Remote Similarity NPD904 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