Natural Product: NPC55597

Natural Product IDNPC55597
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UDTUCCXZNVRBEJ-PBVFJORSSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10338198
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 UDTUCCXZNVRBEJ-PBVFJORSSA-N
Standard InCHI InChI=1S/C16H18O9/c1-5-2-6(18)10-7(19)3-8(20)11(15(10)24-5)16-14(23)13(22)12(21)9(4-17)25-16/h2-3,9,12-14,16-17,19-23H,4H2,1H3/t9-,12-,13+,14-,16+/m1/s1
SMILES Cc1cc(=O)c2c(cc(c(c2o1)[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.1 Volume:   325.553
?
Van der Waals volume.
Dense:   1.088 LogP:   -0.332
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.679
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.091
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   160.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.398 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.023 Fsp3:   0.438
MCE-18:   72.13
?
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:   0.576 Fluc inhibitor:   0.137
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.396
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.424
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.089 Promiscuous compounds:   0.238

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.187 MDCK Permeability:   -5.159
Pgp-inhibitor:   0.0 Pgp-substrate:   0.582
PAMPA:   0.997
?
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):   0.626
20% Bioavailability (F20%):   0.379 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.317 MRP1:   0.718
Plasma Protein Binding (PPB):   84.799% Volume Distribution (VD):   0.057
Fu: 14.682%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.614
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.016
BSEP inhibitor:   0.012

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.061 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.162
HLM stability:   0.031
?
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):  2.869 Half-life (T1/2):  4.437

ADMET: Toxicity

hERG Blockers:  0.012 hERG Blockers (10um):  0.114
Human Hepatotoxicity (H-HT):  0.584 Drug-induced Liver Injury (DILI):  0.922
AMES Toxicity:  0.875 Rat Oral Acute Toxicity:  0.1
Maximum Recommended Daily Dose:  0.116 Skin Sensitization:  0.975
Carcinogencity:  0.371 Eye Corrosion:  0.0
Eye Irritation:  0.861 Respiratory Toxicity:  0.211
Drug-induced Neurotoxicity:  0.006 Ototoxicity:  0.705
Hematotoxicity:  0.194 Drug-induced Nephrotoxicity:  0.301
Genotoxicity:  0.856 RPMI-8226 Immunitoxicity:  0.125
A549 Cytotoxicity:  0.312 Hek293 Cytotoxicity:  0.264
BCF:   0.354
?
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:   2.888
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.308
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.524
?
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
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[1402962]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Flower Buds n.a. n.a. PMID[26977531]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota Fruits n.a. n.a. PMID[31301930]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[34770801]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[36985392]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[37836118]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[39684253]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[39699537]
NPO6783 Avrainvillea rawsonii Species Udoteaceae Eukaryota n.a. n.a. n.a. PMID[7964790]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[8904847]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1032 Piper attenuatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5834 Pellicularia sasakii n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO1456 Bersama abyssinica Species Melianthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2395 Siphonaria australis Species Siphonariidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Essential Oil n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO1032 Piper attenuatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1934 Strychnos triplinervia Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7626 Damnacanthus major Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1934 Strychnos triplinervia Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO577 Lactifluus subvellereus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1032 Piper attenuatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7626 Damnacanthus major Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6072 Andinobates bombetes Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12409 Artemisia jacutica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5834 Pellicularia sasakii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO173 Aconitum sajanense Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2395 Siphonaria australis Species Siphonariidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6041 Lithocolletis coryli n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO9456 Rubus sanctus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6783 Avrainvillea rawsonii Species Udoteaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15735 Galeocerdo arcticus Species Carcharhinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1456 Bersama abyssinica Species Melianthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7383 Puccinia lagenophorae Species Pucciniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1032 Piper attenuatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1934 Strychnos triplinervia Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4504 Cassia jahnii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9718 Cyphelium chrysocephalum Species Caliciaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7626 Damnacanthus major Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8622 Stauntonia hexaphylla Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO577 Lactifluus subvellereus Species Russulaceae 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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 46000.0 nM PMID[26977531]
NPT113 Cell line RAW264.7 Mus musculus IC50 > 60000.0 nM PMID[26977531]

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 NPC55597 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
0.8065 Intermediate Similarity NPC307052
0.6719 Remote Similarity NPC10097
0.6571 Remote Similarity NPC209846
0.6479 Remote Similarity NPC117418
0.6164 Remote Similarity NPC177308
0.5811 Remote Similarity NPC275457
0.5493 Remote Similarity NPC139966
0.5424 Remote Similarity NPC93756
0.5156 Remote Similarity NPC488810

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC55597 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