Natural Product: NPC326386

Natural Product IDNPC326386
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LZIYZPJJVMGBPX-IWWHZBOVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1807143
PubChem CID 56666694
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0003305] Aminosaccharides
            • [CHEMONTID:0000282] Aminoglycosides

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 LZIYZPJJVMGBPX-IWWHZBOVSA-N
Standard InCHI InChI=1S/C22H31NO6/c1-5-12(24)9-21-14-6-7-23(21)13-8-15(21)28-22(14)16(13)10(2)18(29-22)19-17(26-4)11(3)20(25)27-19/h10,12-16,18-19,24H,5-9H2,1-4H3/t10-,12-,13-,14+,15-,16+,18-,19-,21-,22+/m0/s1
SMILES CCC(CC12C3CCN1C4CC2OC35C4C(C(O5)C6C(=C(C(=O)O6)C)OC)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   405.22 Volume:   396.195
?
Van der Waals volume.
Dense:   1.023 LogP:   1.92
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.246
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.07
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   77.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   6.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.696 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   7.204 Fsp3:   0.864
MCE-18:   129.073
?
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:   0.141 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.083
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.012 Promiscuous compounds:   0.015

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.998 MDCK Permeability:   -4.906
Pgp-inhibitor:   0.013 Pgp-substrate:   0.898
PAMPA:   0.773
?
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):   0.194
20% Bioavailability (F20%):   0.342 30% Bioavailability (F30%):   0.489
50% Bioavailability (F50%):   0.889

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.796 MRP1:   0.99
Plasma Protein Binding (PPB):   53.052% Volume Distribution (VD):   0.02
Fu: 54.038%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.103
OATP1B3 inhibitor:   0.693 BCRP inhibitor:   0.062
BSEP inhibitor:   0.552

ADMET: Metabolism

CYP1A2-inhibitor:   0.592 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.597 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.057 CYP2D6-substrate:   0.289
CYP3A4-inhibitor:   0.797 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.654 CYP2C8-inhibitor:   0.0
HLM stability:   0.343
?
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):  14.012 Half-life (T1/2):  2.174

ADMET: Toxicity

hERG Blockers:  0.176 hERG Blockers (10um):  0.577
Human Hepatotoxicity (H-HT):  0.455 Drug-induced Liver Injury (DILI):  0.334
AMES Toxicity:  0.448 Rat Oral Acute Toxicity:  0.386
Maximum Recommended Daily Dose:  0.605 Skin Sensitization:  0.772
Carcinogencity:  0.27 Eye Corrosion:  0.0
Eye Irritation:  0.01 Respiratory Toxicity:  0.292
Drug-induced Neurotoxicity:  0.546 Ototoxicity:  0.847
Hematotoxicity:  0.096 Drug-induced Nephrotoxicity:  0.173
Genotoxicity:  0.423 RPMI-8226 Immunitoxicity:  0.08
A549 Cytotoxicity:  0.029 Hek293 Cytotoxicity:  0.355
BCF:   0.853
?
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:   3.724
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.396
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.523
?
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
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Roots; Stems n.a. n.a. PMID[19374387]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Stems n.a. n.a. PMID[20415428]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. root n.a. PMID[21126060]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Roots Lampang Province, Thailand 2009-APR PMID[21126060]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[21902195]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO221 Stemona aphylla Species Stemonaceae 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
NPT204 Individual protein Acetylcholinesterase Homo sapiens MIC = 50.0 ng PMID[21126060]

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 NPC326386 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
0.6986 Remote Similarity NPC471086
0.6622 Remote Similarity NPC471087
0.6533 Remote Similarity NPC323168
0.6533 Remote Similarity NPC486935
0.6533 Remote Similarity NPC486934
0.6533 Remote Similarity NPC111162
0.6533 Remote Similarity NPC293550
0.5309 Remote Similarity NPC486932
0.5309 Remote Similarity NPC486948
0.5125 Remote Similarity NPC138534
0.5125 Remote Similarity NPC486937
0.5122 Remote Similarity NPC486951

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC326386 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