Natural Product: NPC116780

Natural Product IDNPC116780
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GJDGTVUZKDKLQP-GAGVYUBLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 21636226
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0004165] Phenolic glycosides

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 GJDGTVUZKDKLQP-GAGVYUBLSA-N
Standard InCHI InChI=1S/C17H24O8/c1-4-5-9-6-10(22-2)16(11(7-9)23-3)25-17-15(21)14(20)13(19)12(8-18)24-17/h4,6-7,12-15,17-21H,1,5,8H2,2-3H3/t12-,13-,14+,15-,17+/m1/s1
SMILES C=CCc1cc(c(c(c1)OC)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.15 Volume:   345.251
?
Van der Waals volume.
Dense:   1.032 LogP:   0.393
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.783
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.434
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   13.0
TPSA:   117.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.488 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.665 Fsp3:   0.529
MCE-18:   50.769
?
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:   0.396 Fluc inhibitor:   0.034
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.019
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.079
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.245 Promiscuous compounds:   0.05

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.371 MDCK Permeability:   -4.873
Pgp-inhibitor:   0.005 Pgp-substrate:   0.005
PAMPA:   0.237
?
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):   0.274
20% Bioavailability (F20%):   0.337 30% Bioavailability (F30%):   0.965
50% Bioavailability (F50%):   0.911

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.555 MRP1:   0.057
Plasma Protein Binding (PPB):   75.581% Volume Distribution (VD):   -0.112
Fu: 24.601%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.35
BSEP inhibitor:   0.247

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.477 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.151 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.012 CYP2D6-substrate:   0.748
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.464
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.014
?
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):  3.127 Half-life (T1/2):  3.103

ADMET: Toxicity

hERG Blockers:  0.026 hERG Blockers (10um):  0.195
Human Hepatotoxicity (H-HT):  0.571 Drug-induced Liver Injury (DILI):  0.804
AMES Toxicity:  0.794 Rat Oral Acute Toxicity:  0.048
Maximum Recommended Daily Dose:  0.039 Skin Sensitization:  0.996
Carcinogencity:  0.341 Eye Corrosion:  0.001
Eye Irritation:  0.336 Respiratory Toxicity:  0.084
Drug-induced Neurotoxicity:  0.101 Ototoxicity:  0.847
Hematotoxicity:  0.278 Drug-induced Nephrotoxicity:  0.441
Genotoxicity:  0.249 RPMI-8226 Immunitoxicity:  0.095
A549 Cytotoxicity:  0.161 Hek293 Cytotoxicity:  0.219
BCF:   0.643
?
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:   3.11
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.779
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.692
?
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
NPO4324 Verbascum phlomoides Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15421 Aniba puchury-minor Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4324 Verbascum phlomoides Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4324 Verbascum phlomoides Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4324 Verbascum phlomoides Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15421 Aniba puchury-minor Species Lauraceae 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 NPC116780 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
0.7959 Intermediate Similarity NPC69513
0.7692 Intermediate Similarity NPC270849
0.7647 Intermediate Similarity NPC215833
0.7308 Intermediate Similarity NPC9912
0.72 Intermediate Similarity NPC299144
0.6863 Remote Similarity NPC60589
0.6863 Remote Similarity NPC469708
0.6852 Remote Similarity NPC49074
0.6792 Remote Similarity NPC48863
0.6792 Remote Similarity NPC251981
0.6792 Remote Similarity NPC13745
0.6727 Remote Similarity NPC162093
0.6607 Remote Similarity NPC210478
0.66 Remote Similarity NPC217854
0.6429 Remote Similarity NPC472024
0.6346 Remote Similarity NPC152722
0.6316 Remote Similarity NPC210015
0.6271 Remote Similarity NPC232673
0.6167 Remote Similarity NPC470236
0.614 Remote Similarity NPC19470
0.6102 Remote Similarity NPC95392
0.6102 Remote Similarity NPC84013
0.6102 Remote Similarity NPC55715
0.6102 Remote Similarity NPC35877
0.6094 Remote Similarity NPC479447
0.6078 Remote Similarity NPC276195
0.6034 Remote Similarity NPC26653
0.6034 Remote Similarity NPC80600
0.5893 Remote Similarity NPC95292
0.5781 Remote Similarity NPC210192
0.5781 Remote Similarity NPC475096
0.569 Remote Similarity NPC218685
0.5667 Remote Similarity NPC479029
0.5652 Remote Similarity NPC199539
0.5614 Remote Similarity NPC166040
0.56 Remote Similarity NPC228907
0.5588 Remote Similarity NPC61594
0.5556 Remote Similarity NPC153149
0.5556 Remote Similarity NPC134260
0.5536 Remote Similarity NPC608788
0.5507 Remote Similarity NPC56735
0.5493 Remote Similarity NPC605526
0.5484 Remote Similarity NPC97326
0.5469 Remote Similarity NPC479030
0.5455 Remote Similarity NPC216129
0.5455 Remote Similarity NPC130449
0.5455 Remote Similarity NPC25817
0.5455 Remote Similarity NPC248132
0.541 Remote Similarity NPC248355
0.5385 Remote Similarity NPC164857
0.5333 Remote Similarity NPC23084
0.5323 Remote Similarity NPC55040
0.5323 Remote Similarity NPC104167
0.5286 Remote Similarity NPC227902
0.5273 Remote Similarity NPC192810
0.5273 Remote Similarity NPC294470
0.5263 Remote Similarity NPC12308
0.5263 Remote Similarity NPC226712
0.5254 Remote Similarity NPC40377
0.5254 Remote Similarity NPC310661
0.5238 Remote Similarity NPC302378
0.5231 Remote Similarity NPC486107
0.5224 Remote Similarity NPC485147
0.5185 Remote Similarity NPC212729
0.5185 Remote Similarity NPC604498
0.5172 Remote Similarity NPC145900
0.5152 Remote Similarity NPC146803
0.5152 Remote Similarity NPC474044
0.5147 Remote Similarity NPC148273
0.5143 Remote Similarity NPC51328
0.5143 Remote Similarity NPC55158
0.5091 Remote Similarity NPC269242
0.5088 Remote Similarity NPC190730
0.5088 Remote Similarity NPC609376
0.5082 Remote Similarity NPC479028
0.5082 Remote Similarity NPC479031
0.5075 Remote Similarity NPC189115
0.5075 Remote Similarity NPC475084
0.507 Remote Similarity NPC79957
0.507 Remote Similarity NPC147596
0.5068 Remote Similarity NPC476203

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC116780 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
0.5263 Remote Similarity NPD1091 Pre-clinical

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