Natural Product: NPC13748

Natural Product IDNPC13748
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VTVARPTUBCBNJX-UJPOAAIJSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11809239
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:0002207] O-glycosyl 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 VTVARPTUBCBNJX-UJPOAAIJSA-N
Standard InCHI InChI=1S/C14H20O8/c15-7-9-10(17)11(18)12(19)13(22-9)21-6-5-14(20)3-1-8(16)2-4-14/h1-4,9-13,15,17-20H,5-7H2/t9-,10-,11+,12-,13-/m1/s1
SMILES C1=CC(C=CC1=O)(CCO[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.12 Volume:   296.0
?
Van der Waals volume.
Dense:   1.068 LogP:   -1.451
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.886
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.713
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   13.0
TPSA:   136.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.379 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.268 Fsp3:   0.643
MCE-18:   37.826
?
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:   0.35 Fluc inhibitor:   0.033
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.24
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.017
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.345 Promiscuous compounds:   0.344

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.723 MDCK Permeability:   -5.094
Pgp-inhibitor:   0.0 Pgp-substrate:   0.206
PAMPA:   0.98
?
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):   0.866
20% Bioavailability (F20%):   0.074 30% Bioavailability (F30%):   0.975
50% Bioavailability (F50%):   0.857

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.775 MRP1:   0.065
Plasma Protein Binding (PPB):   37.373% Volume Distribution (VD):   -0.502
Fu: 60.965%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.898
OATP1B3 inhibitor:   0.974 BCRP inhibitor:   0.009
BSEP inhibitor:   0.012

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.006 CYP3A4-substrate:   0.124
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.076
HLM stability:   0.222
?
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):  3.158 Half-life (T1/2):  2.546

ADMET: Toxicity

hERG Blockers:  0.02 hERG Blockers (10um):  0.081
Human Hepatotoxicity (H-HT):  0.663 Drug-induced Liver Injury (DILI):  0.425
AMES Toxicity:  0.829 Rat Oral Acute Toxicity:  0.051
Maximum Recommended Daily Dose:  0.062 Skin Sensitization:  0.996
Carcinogencity:  0.331 Eye Corrosion:  0.01
Eye Irritation:  0.805 Respiratory Toxicity:  0.064
Drug-induced Neurotoxicity:  0.057 Ototoxicity:  0.85
Hematotoxicity:  0.557 Drug-induced Nephrotoxicity:  0.521
Genotoxicity:  0.587 RPMI-8226 Immunitoxicity:  0.085
A549 Cytotoxicity:  0.079 Hek293 Cytotoxicity:  0.217
BCF:   0.617
?
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:   3.447
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.532
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.952
?
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
NPO6987 Tolypothrix byssoidea Species Tolypothrichaceae Bacteria n.a. n.a. n.a. PMID[11429991]
NPO23838 Kitasatospora kifunensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[17191679]
NPO6987 Tolypothrix byssoidea Species Tolypothrichaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO11437 Alluaudia ascendens Species Didiereaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8231 Jaspis digonoxea Species Ancorinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5788 Millingtonia hortensis Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO228 Physostigma venenosum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5788 Millingtonia hortensis Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO228 Physostigma venenosum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO228 Physostigma venenosum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5788 Millingtonia hortensis Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5445 Euonymus nanus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11437 Alluaudia ascendens Species Didiereaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6987 Tolypothrix byssoidea Species Tolypothrichaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO23838 Kitasatospora kifunensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO6710 Sinapis nigra Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO228 Physostigma venenosum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10826 Rabdosia weisiensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8719 Fusarium vasinfectum Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11189 Anabaena sphaerica Species Nostocaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO4489 Achillea serbica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10196 Echinocereus blanckii Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5788 Millingtonia hortensis Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8231 Jaspis digonoxea Species Ancorinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4214 Centaurea collina Species Asteraceae 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 NPC13748 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
0.5652 Remote Similarity NPC233726
0.5538 Remote Similarity NPC474641
0.551 Remote Similarity NPC13143
0.551 Remote Similarity NPC294813
0.5417 Remote Similarity NPC155457
0.5294 Remote Similarity NPC252114
0.5227 Remote Similarity NPC124963
0.52 Remote Similarity NPC606861
0.52 Remote Similarity NPC607126
0.5111 Remote Similarity NPC326533
0.5088 Remote Similarity NPC280367

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC13748 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