Natural Product: NPC75435

Natural Product IDNPC75435
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CLVUFWXGNIFGNC-OVHBTUCOSA-N
IUPAC Name n.a.
Synonyms Alpha-Homonojirimycin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL501355
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000195] Piperidines

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 CLVUFWXGNIFGNC-OVHBTUCOSA-N
Standard InCHI InChI=1S/C7H15NO5/c9-1-3-5(11)7(13)6(12)4(2-10)8-3/h3-13H,1-2H2/t3-,4-,5-,6+,7+/m1/s1
SMILES C([C@@H]1[C@H]([C@@H]([C@H]([C@@H](CO)N1)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   193.1 Volume:   176.02
?
Van der Waals volume.
Dense:   1.097 LogP:   -2.226
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -1.821
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   0.525
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   6.0
TPSA:   113.18
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   6.0 Rings:   1.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.27 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.115 Fsp3:   1.0
MCE-18:   21.714
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.045 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.033
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.316 Promiscuous compounds:   0.289

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.34 MDCK Permeability:   -4.79
Pgp-inhibitor:   0.0 Pgp-substrate:   0.578
PAMPA:   0.992
?
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):   0.673
20% Bioavailability (F20%):   0.296 30% Bioavailability (F30%):   0.804
50% Bioavailability (F50%):   0.872

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.056 MRP1:   0.108
Plasma Protein Binding (PPB):   23.065% Volume Distribution (VD):   -0.508
Fu: 83.739%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.528
OATP1B3 inhibitor:   0.724 BCRP inhibitor:   0.027
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.703
HLM stability:   0.017
?
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):  3.368 Half-life (T1/2):  2.061

ADMET: Toxicity

hERG Blockers:  0.012 hERG Blockers (10um):  0.128
Human Hepatotoxicity (H-HT):  0.403 Drug-induced Liver Injury (DILI):  0.053
AMES Toxicity:  0.414 Rat Oral Acute Toxicity:  0.015
Maximum Recommended Daily Dose:  0.003 Skin Sensitization:  0.731
Carcinogencity:  0.106 Eye Corrosion:  0.013
Eye Irritation:  0.784 Respiratory Toxicity:  0.004
Drug-induced Neurotoxicity:  0.005 Ototoxicity:  0.938
Hematotoxicity:  0.229 Drug-induced Nephrotoxicity:  0.679
Genotoxicity:  0.007 RPMI-8226 Immunitoxicity:  0.041
A549 Cytotoxicity:  0.008 Hek293 Cytotoxicity:  0.016
BCF:   0.148
?
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:   1.42
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   2.529
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   1.88
?
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
NPO33446 aglaonema treubii Species Araceae Eukaryota n.a. n.a. n.a. PMID[10560746]
NPO16194 Morus bombycis Species Moraceae Eukaryota n.a. root n.a. PMID[17396934]
NPO25280 Suregada glomerulata Species Euphorbiaceae Eukaryota Roots n.a. n.a. PMID[18205316]
NPO12473 Castanospermum australe Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[2213032]
NPO25280 Suregada glomerulata Species Euphorbiaceae Eukaryota leaves n.a. n.a. PMID[23993676]
NPO21156 Xanthocercis zambesiaca Species Fabaceae Eukaryota n.a. leaf n.a. PMID[9157194]
NPO21156 Xanthocercis zambesiaca Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9157194]
NPO16194 Morus bombycis Species Moraceae Eukaryota n.a. n.a. n.a. PMID[9544568]
NPO33446 aglaonema treubii Species Araceae Eukaryota n.a. n.a. n.a. PMID[9544568]
NPO12473 Castanospermum australe Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9544568]
NPO21156 Xanthocercis zambesiaca Species Fabaceae Eukaryota n.a. root n.a. PMID[9544568]
NPO21156 Xanthocercis zambesiaca Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9544568]
NPO25280 Suregada glomerulata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21156 Xanthocercis zambesiaca Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12473 Castanospermum australe Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16194 Morus bombycis Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16194 Morus bombycis Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16194 Morus bombycis Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16194 Morus bombycis Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16194 Morus bombycis Species Moraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25280 Suregada glomerulata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21156 Xanthocercis zambesiaca Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16194 Morus bombycis Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12473 Castanospermum australe 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
NPT1055 Individual protein Neutral alpha-glucosidase C Mus musculus IC50 = 340.0 nM PubChem BioAssay data set
NPT1050 Individual protein Trehalase Rattus norvegicus IC50 = 34000.0 nM PMID[22934537]
NPT509 Individual protein Beta-galactosidase Bos taurus Inhibition < 50.0 % PMID[23398362]
NPT497 Individual protein Maltase-glucoamylase Homo sapiens IC50 = 40.0 nM DOI[10.6019/CHEMBL1201861]
NPT501 Individual protein Alpha-galactosidase A Homo sapiens Inhibition < 50.0 % PMID[17286431]
NPT462 Individual protein Sucrase-isomaltase Rattus norvegicus IC50 = 700.0 nM PMID[26003344]
NPT462 Individual protein Sucrase-isomaltase Rattus norvegicus IC50 = 170.0 nM PMID[16274989]
NPT6631 Individual protein Neutral alpha-glucosidase C Homo sapiens Inhibition < 50.0 % PMID[23398362]
NPT61 Individual protein Beta-glucocerebrosidase Homo sapiens Inhibition < 50.0 % PMID[19128055]
NPT6372 Individual protein Alpha-galactosidase A Rattus norvegicus Inhibition < 50.0 % PMID[23398362]
NPT60 Individual protein Lysosomal alpha-glucosidase Homo sapiens IC50 = 1000.0 nM PMID[10869195]
NPT3906 Individual protein Glycogen debranching enzyme Oryctolagus cuniculus IC50 = 110.0 nM PMID[15332848]
NPT60 Individual protein Lysosomal alpha-glucosidase Homo sapiens IC50 = 100.0 nM PubChem BioAssay data set
NPT503 Individual protein Alpha-L-fucosidase I Homo sapiens Inhibition < 50.0 % PMID[22934537]
NPT671 Individual protein Acidic alpha-glucosidase Rattus norvegicus IC50 = 340.0 nM PMID[15911254]
NPT671 Individual protein Acidic alpha-glucosidase Rattus norvegicus IC50 = 170.0 nM PMID[22934537]
NPT671 Individual protein Acidic alpha-glucosidase Rattus norvegicus IC50 = 260.0 nM PMID[22934537]
NPT5153 Individual protein Alpha-L-fucosidase I Rattus norvegicus Inhibition < 50.0 % PMID[22934537]
NPT671 Individual protein Acidic alpha-glucosidase Rattus norvegicus IC50 = 700.0 nM PMID[22934537]
NPT671 Individual protein Acidic alpha-glucosidase Rattus norvegicus IC50 = 8400.0 nM PMID[22506638]
NPT671 Individual protein Acidic alpha-glucosidase Rattus norvegicus IC50 = 80.0 nM PMID[26003344]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Inhibition < 50.0 % PMID[22934537]
NPT2 Others Unspecified n.a. IC50 = 90.0 nM PMID[1791472]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity = 161.2 mg/dl PMID[21070010]
NPT32 Organism Mus musculus Mus musculus Activity = 176.4 mg/dl PMID[10514305]
NPT32 Organism Mus musculus Mus musculus Activity = 129.3 mg/dl PMID[10514305]
NPT32 Organism Mus musculus Mus musculus Activity = 136.4 mg/dl PMID[22018878]
NPT32 Organism Mus musculus Mus musculus Activity = 149.9 mg/dl PMID[10514323]
NPT32 Organism Mus musculus Mus musculus Activity = 126.0 mg/dl PMID[17958396]





 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 NPC75435 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
1.0 High Similarity NPC223386
1.0 High Similarity NPC142290
1.0 High Similarity NPC198341
1.0 High Similarity NPC471892
1.0 High Similarity NPC471780
0.7273 Intermediate Similarity NPC286851
0.7273 Intermediate Similarity NPC303798
0.7222 Intermediate Similarity NPC62507
0.7222 Intermediate Similarity NPC602743
0.6667 Remote Similarity NPC268922
0.5714 Remote Similarity NPC474014
0.5714 Remote Similarity NPC30126
0.5714 Remote Similarity NPC57846
0.5217 Remote Similarity NPC474928
0.5161 Remote Similarity NPC471418

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC75435 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
NPD

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