Natural Product: NPC60589

Natural Product IDNPC60589
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2R,3S,4S,5R,6S)-2-(Hydroxymethyl)-6-(4-Prop-2-Enylphenoxy)Oxane-3,4,5-Triol
IUPAC Name (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-(4-prop-2-enylphenoxy)oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL179783
PubChem CID 44390556
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 BGWWYZXBGAKMRB-UXXRCYHCSA-N
Standard InCHI InChI=1S/C15H20O6/c1-2-3-9-4-6-10(7-5-9)20-15-14(19)13(18)12(17)11(8-16)21-15/h2,4-7,11-19H,1,3,8H2/t11-,12-,13+,14-,15-/m1/s1
SMILES C=CCc1ccc(cc1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   296.13 Volume:   293.079
?
Van der Waals volume.
Dense:   1.01 LogP:   0.713
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.118
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.455
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   13.0
TPSA:   99.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.552 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.492 Fsp3:   0.467
MCE-18:   44.909
?
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:   0.423 Fluc inhibitor:   0.086
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.021
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.011
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.393 Promiscuous compounds:   0.022

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.563 MDCK Permeability:   -4.983
Pgp-inhibitor:   0.007 Pgp-substrate:   0.002
PAMPA:   0.561
?
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):   0.835
20% Bioavailability (F20%):   0.634 30% Bioavailability (F30%):   0.986
50% Bioavailability (F50%):   0.915

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.232 MRP1:   0.011
Plasma Protein Binding (PPB):   73.441% Volume Distribution (VD):   -0.211
Fu: 25.938%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.196
BSEP inhibitor:   0.335

ADMET: Metabolism

CYP1A2-inhibitor:   0.012 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.079 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.015 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.006
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.337
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.013
?
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):  2.922 Half-life (T1/2):  2.954

ADMET: Toxicity

hERG Blockers:  0.035 hERG Blockers (10um):  0.21
Human Hepatotoxicity (H-HT):  0.531 Drug-induced Liver Injury (DILI):  0.851
AMES Toxicity:  0.877 Rat Oral Acute Toxicity:  0.034
Maximum Recommended Daily Dose:  0.016 Skin Sensitization:  0.997
Carcinogencity:  0.306 Eye Corrosion:  0.005
Eye Irritation:  0.62 Respiratory Toxicity:  0.053
Drug-induced Neurotoxicity:  0.053 Ototoxicity:  0.835
Hematotoxicity:  0.231 Drug-induced Nephrotoxicity:  0.564
Genotoxicity:  0.204 RPMI-8226 Immunitoxicity:  0.061
A549 Cytotoxicity:  0.171 Hek293 Cytotoxicity:  0.151
BCF:   0.614
?
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:   4.569
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.792
?
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
NPO26351 Agastache rugosa Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[11908994]
NPO28679 Prunus mume Species Rosaceae Eukaryota flowers n.a. n.a. PMID[12193020]
NPO26351 Agastache rugosa Species Lamiaceae Eukaryota n.a. root n.a. PMID[1823989]
NPO28679 Prunus mume Species Rosaceae Eukaryota fruits n.a. n.a. PMID[24485782]
NPO18983 Cleidion brevipetiolatum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[31419126]
NPO26351 Agastache rugosa Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[31747281]
NPO26351 Agastache rugosa Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38791403]
NPO26351 Agastache rugosa Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[8594148]
NPO26351 Agastache rugosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18983 Cleidion brevipetiolatum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26351 Agastache rugosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26351 Agastache rugosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28679 Prunus mume Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26351 Agastache rugosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18983 Cleidion brevipetiolatum Species Euphorbiaceae 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 > 50000.0 nM PMID[31419126]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 18300.0 nM PMID[31747281]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus IC50 > 100000.0 nM PMID[15780639]
NPT32 Organism Mus musculus Mus musculus Inhibition = 6.0 % PMID[15780639]





 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 NPC60589 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
1.0 High Similarity NPC469708
0.7917 Intermediate Similarity NPC9912
0.76 Intermediate Similarity NPC270849
0.76 Intermediate Similarity NPC19470
0.7391 Intermediate Similarity NPC294470
0.7333 Intermediate Similarity NPC212729
0.7333 Intermediate Similarity NPC604498
0.7174 Intermediate Similarity NPC269242
0.6939 Remote Similarity NPC200092
0.6792 Remote Similarity NPC210015
0.6735 Remote Similarity NPC609376
0.6604 Remote Similarity NPC479769
0.6471 Remote Similarity NPC80098
0.6296 Remote Similarity NPC472024
0.6296 Remote Similarity NPC251102
0.6296 Remote Similarity NPC210298
0.6296 Remote Similarity NPC604356
0.625 Remote Similarity NPC142319
0.6182 Remote Similarity NPC26080
0.6182 Remote Similarity NPC165686
0.6167 Remote Similarity NPC210192
0.6111 Remote Similarity NPC218685
0.6087 Remote Similarity NPC228907
0.6034 Remote Similarity NPC604013
0.6 Remote Similarity NPC287429
0.5932 Remote Similarity NPC479768
0.5893 Remote Similarity NPC26653
0.5893 Remote Similarity NPC80600
0.5846 Remote Similarity NPC79957
0.5769 Remote Similarity NPC198798
0.5769 Remote Similarity NPC604439
0.5714 Remote Similarity NPC479028
0.5714 Remote Similarity NPC479031
0.5686 Remote Similarity NPC153149
0.566 Remote Similarity NPC12308
0.566 Remote Similarity NPC226712
0.566 Remote Similarity NPC608788
0.5645 Remote Similarity NPC189115
0.5636 Remote Similarity NPC310661
0.5625 Remote Similarity NPC186406
0.5614 Remote Similarity NPC481303
0.56 Remote Similarity NPC276195
0.5593 Remote Similarity NPC97326
0.5577 Remote Similarity NPC25817
0.5556 Remote Similarity NPC69513
0.549 Remote Similarity NPC217854
0.5455 Remote Similarity NPC214454
0.5455 Remote Similarity NPC166040
0.5455 Remote Similarity NPC610709
0.5439 Remote Similarity NPC205054
0.5439 Remote Similarity NPC23084
0.541 Remote Similarity NPC294166
0.541 Remote Similarity NPC134260
0.541 Remote Similarity NPC115022
0.5397 Remote Similarity NPC248119
0.5397 Remote Similarity NPC106944
0.5385 Remote Similarity NPC192810
0.5362 Remote Similarity NPC480635
0.5357 Remote Similarity NPC40377
0.5357 Remote Similarity NPC215833
0.5323 Remote Similarity NPC186418
0.5323 Remote Similarity NPC8497
0.5323 Remote Similarity NPC479374
0.5312 Remote Similarity NPC264381
0.5312 Remote Similarity NPC259767
0.5294 Remote Similarity NPC160882
0.5283 Remote Similarity NPC9248
0.5273 Remote Similarity NPC221090
0.5254 Remote Similarity NPC248355
0.5246 Remote Similarity NPC100389
0.5246 Remote Similarity NPC146540
0.5238 Remote Similarity NPC474044
0.5238 Remote Similarity NPC121001
0.5231 Remote Similarity NPC116229
0.5231 Remote Similarity NPC471029
0.5231 Remote Similarity NPC601944
0.5231 Remote Similarity NPC606353
0.5192 Remote Similarity NPC484157
0.5185 Remote Similarity NPC299144
0.5179 Remote Similarity NPC166168
0.5172 Remote Similarity NPC606892
0.5167 Remote Similarity NPC222455
0.5167 Remote Similarity NPC55040
0.5161 Remote Similarity NPC242028
0.5161 Remote Similarity NPC203230
0.5161 Remote Similarity NPC469661
0.5156 Remote Similarity NPC175275
0.5085 Remote Similarity NPC214910
0.5085 Remote Similarity NPC164599
0.5085 Remote Similarity NPC210478
0.5082 Remote Similarity NPC302378
0.5082 Remote Similarity NPC59324
0.5082 Remote Similarity NPC85799
0.5082 Remote Similarity NPC303422
0.5082 Remote Similarity NPC218003
0.5082 Remote Similarity NPC34456
0.5079 Remote Similarity NPC479030
0.5079 Remote Similarity NPC37468
0.5079 Remote Similarity NPC202700
0.5079 Remote Similarity NPC185778
0.5077 Remote Similarity NPC178851
0.5077 Remote Similarity NPC177742
0.5077 Remote Similarity NPC295970
0.5077 Remote Similarity NPC57587

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC60589 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
0.566 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