Natural Product: NPC522596

Natural Product IDNPC522596
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{S},3~{R},4~{S},5~{S},6~{R})-2-(4-hydroxy-2-isopropyl-3-methyl-phenoxy)-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol
IUPAC Name (2~{S},3~{R},4~{S},5~{S},6~{R})-2-(4-hydroxy-2-isopropyl-3-methyl-phenoxy)-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 AJADLMIVHUIITC-YMILTQATSA-N
Standard InCHI InChI=1S/C16H24O7/c1-7(2)12-8(3)9(18)4-5-10(12)22-16-15(21)14(20)13(19)11(6-17)23-16/h4-5,7,11,13-21H,6H2,1-3H3/t11-,13-,14+,15-,16-/m1/s1
SMILES CC1=C(O)C=CC(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)=C1C(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.15 Volume:   321.802
?
Van der Waals volume.
Dense:   1.02 LogP:   0.628
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.309
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.951
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   119.61
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.528 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.802 Fsp3:   0.625
MCE-18:   54.154
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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:   0.504 Fluc inhibitor:   0.01
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.243
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.027
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.212 Promiscuous compounds:   0.112

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.641 MDCK Permeability:   -5.133
Pgp-inhibitor:   0.001 Pgp-substrate:   0.053
PAMPA:   0.475
?
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):   0.419
20% Bioavailability (F20%):   0.611 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.101 MRP1:   0.877
Plasma Protein Binding (PPB):   74.538% Volume Distribution (VD):   -0.009
Fu: 25.993%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.085
BSEP inhibitor:   0.14

ADMET: Metabolism

CYP1A2-inhibitor:   0.075 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.096 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.034
CYP3A4-inhibitor:   0.092 CYP3A4-substrate:   0.052
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.57
HLM stability:   0.055
?
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):  3.346 Half-life (T1/2):  2.778

ADMET: Toxicity

hERG Blockers:  0.028 hERG Blockers (10um):  0.163
Human Hepatotoxicity (H-HT):  0.712 Drug-induced Liver Injury (DILI):  0.623
AMES Toxicity:  0.847 Rat Oral Acute Toxicity:  0.048
Maximum Recommended Daily Dose:  0.026 Skin Sensitization:  0.996
Carcinogencity:  0.368 Eye Corrosion:  0.001
Eye Irritation:  0.503 Respiratory Toxicity:  0.077
Drug-induced Neurotoxicity:  0.024 Ototoxicity:  0.941
Hematotoxicity:  0.425 Drug-induced Nephrotoxicity:  0.706
Genotoxicity:  0.184 RPMI-8226 Immunitoxicity:  0.079
A549 Cytotoxicity:  0.155 Hek293 Cytotoxicity:  0.215
BCF:   0.591
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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:   3.184
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.678
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.876
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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
NPO52176 Origanum syriacum Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[37049808]
NPO52176 Origanum syriacum 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 NPC522596 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
0.6897 Remote Similarity NPC475628
0.625 Remote Similarity NPC40377
0.623 Remote Similarity NPC611586
0.6094 Remote Similarity NPC177742
0.6071 Remote Similarity NPC604209
0.6 Remote Similarity NPC106025
0.5962 Remote Similarity NPC142319
0.5902 Remote Similarity NPC97326
0.5806 Remote Similarity NPC199335
0.5806 Remote Similarity NPC477240
0.5789 Remote Similarity NPC214454
0.5763 Remote Similarity NPC23084
0.5738 Remote Similarity NPC599943
0.5735 Remote Similarity NPC61594
0.5714 Remote Similarity NPC134260
0.5714 Remote Similarity NPC190217
0.5652 Remote Similarity NPC56735
0.5652 Remote Similarity NPC147596
0.5636 Remote Similarity NPC9248
0.5636 Remote Similarity NPC152722
0.5538 Remote Similarity NPC600107
0.5522 Remote Similarity NPC271385
0.5522 Remote Similarity NPC146837
0.55 Remote Similarity NPC205054
0.549 Remote Similarity NPC228907
0.5455 Remote Similarity NPC210192
0.5455 Remote Similarity NPC302989
0.5455 Remote Similarity NPC294470
0.5439 Remote Similarity NPC12308
0.5439 Remote Similarity NPC226712
0.5439 Remote Similarity NPC608788
0.5417 Remote Similarity NPC476203
0.5397 Remote Similarity NPC609355
0.5385 Remote Similarity NPC610808
0.537 Remote Similarity NPC212729
0.537 Remote Similarity NPC604498
0.5362 Remote Similarity NPC259182
0.5352 Remote Similarity NPC607365
0.5345 Remote Similarity NPC221090
0.5345 Remote Similarity NPC69513
0.5333 Remote Similarity NPC218685
0.5303 Remote Similarity NPC604892
0.5294 Remote Similarity NPC278329
0.5294 Remote Similarity NPC92054
0.5294 Remote Similarity NPC5029
0.5294 Remote Similarity NPC30432
0.5294 Remote Similarity NPC601828
0.5294 Remote Similarity NPC606849
0.5273 Remote Similarity NPC217854
0.5273 Remote Similarity NPC269242
0.5273 Remote Similarity NPC484157
0.5263 Remote Similarity NPC299144
0.5263 Remote Similarity NPC60589
0.5263 Remote Similarity NPC469708
0.5254 Remote Similarity NPC166168
0.5246 Remote Similarity NPC19470
0.5246 Remote Similarity NPC606892
0.5238 Remote Similarity NPC222455
0.5211 Remote Similarity NPC257963
0.5179 Remote Similarity NPC192810
0.5172 Remote Similarity NPC200092
0.5167 Remote Similarity NPC310661
0.5167 Remote Similarity NPC215833
0.5161 Remote Similarity NPC214910
0.5161 Remote Similarity NPC26080
0.5161 Remote Similarity NPC210015
0.5161 Remote Similarity NPC165686
0.5161 Remote Similarity NPC481303
0.5156 Remote Similarity NPC607971
0.5152 Remote Similarity NPC111536
0.5152 Remote Similarity NPC479374
0.5147 Remote Similarity NPC99233
0.5143 Remote Similarity NPC212099
0.5143 Remote Similarity NPC88484
0.5143 Remote Similarity NPC76128
0.5091 Remote Similarity NPC276195
0.5079 Remote Similarity NPC609351
0.5077 Remote Similarity NPC603686
0.5075 Remote Similarity NPC121001
0.5072 Remote Similarity NPC605700
0.507 Remote Similarity NPC260604

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC522596 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
0.5439 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