Natural Product: NPC592659

Natural Product IDNPC592659
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 [(2~{S})-2-tetradecanoyloxy-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-propyl] octadecanoate
IUPAC Name [(2~{S})-2-tetradecanoyloxy-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-propyl] octadecanoate
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 LGYCXVJXWRPVSQ-GSYQMMAASA-N
Standard InCHI InChI=1S/C47H88O15/c1-3-5-7-9-11-13-15-16-17-18-20-21-23-25-27-29-38(49)57-32-35(60-39(50)30-28-26-24-22-19-14-12-10-8-6-4-2)33-58-46-45(56)43(54)41(52)37(62-46)34-59-47-44(55)42(53)40(51)36(31-48)61-47/h35-37,40-48,51-56H,3-34H2,1-2H3/t35-,36-,37-,40-,41-,42+,43+,44-,45-,46+,47+/m1/s1
SMILES CCCCCCCCCCCCCCCCCC(=O)OC[C@H](CO[C@H]1O[C@H](CO[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@H](O)[C@H]1O)OC(=O)CCCCCCCCCCCCC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   892.61 Volume:   930.935
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Van der Waals volume.
Dense:   0.959 LogP:   7.008
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.56
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.262
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The logarithm of aqueous solubility value.
Rotatable Bonds:   40.0 Rigid Bonds:   14.0
TPSA:   231.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   15.0
H-Bond Donor:   7.0 Rings:   2.0
Heavy Atoms:   15.0

MedChem Properties

QED Drug-Likeness Score:   0.028 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.944 Fsp3:   0.957
MCE-18:   42.13
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MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.997 Fluc inhibitor:   0.012
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.29 Promiscuous compounds:   0.066

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.563 MDCK Permeability:   -4.745
Pgp-inhibitor:   0.0 Pgp-substrate:   0.879
PAMPA:   0.001
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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):   0.803
20% Bioavailability (F20%):   0.987 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.919
Plasma Protein Binding (PPB):   97.875% Volume Distribution (VD):   0.429
Fu: 1.823%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.625
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.602
BSEP inhibitor:   0.933

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.958
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.186
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.976
CYP3A4-inhibitor:   0.534 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.004
?
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):  2.172 Half-life (T1/2):  5.872

ADMET: Toxicity

hERG Blockers:  0.277 hERG Blockers (10um):  0.687
Human Hepatotoxicity (H-HT):  0.484 Drug-induced Liver Injury (DILI):  0.463
AMES Toxicity:  0.356 Rat Oral Acute Toxicity:  0.002
Maximum Recommended Daily Dose:  0.026 Skin Sensitization:  1.0
Carcinogencity:  0.032 Eye Corrosion:  0.0
Eye Irritation:  0.369 Respiratory Toxicity:  0.127
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.958
Hematotoxicity:  0.086 Drug-induced Nephrotoxicity:  0.972
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.217
A549 Cytotoxicity:  0.968 Hek293 Cytotoxicity:  0.143
BCF:   0.123
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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:   4.96
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.834
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.185
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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
NPO64469 Ocimum sanctum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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 NPC592659 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
0.902 High Similarity NPC488690
0.8947 High Similarity NPC156089
0.8226 Intermediate Similarity NPC470313
0.8226 Intermediate Similarity NPC473500
0.8226 Intermediate Similarity NPC611497
0.807 Intermediate Similarity NPC488689
0.7903 Intermediate Similarity NPC38295
0.7667 Intermediate Similarity NPC21693
0.7455 Intermediate Similarity NPC285003
0.7273 Intermediate Similarity NPC12040
0.7101 Intermediate Similarity NPC22558
0.7097 Intermediate Similarity NPC236649
0.7 Intermediate Similarity NPC476611
0.6949 Remote Similarity NPC83839
0.6875 Remote Similarity NPC110813
0.6613 Remote Similarity NPC488693
0.6508 Remote Similarity NPC331437
0.6364 Remote Similarity NPC133377
0.6316 Remote Similarity NPC206601
0.629 Remote Similarity NPC163812
0.6286 Remote Similarity NPC476612
0.6286 Remote Similarity NPC476613
0.6129 Remote Similarity NPC250619
0.6038 Remote Similarity NPC145112
0.6029 Remote Similarity NPC488694
0.5775 Remote Similarity NPC488692
0.569 Remote Similarity NPC147292
0.5574 Remote Similarity NPC241265
0.5541 Remote Similarity NPC475425
0.5469 Remote Similarity NPC143446
0.541 Remote Similarity NPC76881
0.5357 Remote Similarity NPC606861
0.5357 Remote Similarity NPC607126
0.5294 Remote Similarity NPC55678

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC592659 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
0.5294 Remote Similarity NPD6125 Phase 4
0.5082 Remote Similarity NPD3181 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