Natural Product: NPC298847

Natural Product IDNPC298847
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3R)-3-(3-Hydroxy-4-Methoxyphenyl)-8-[(2S,3R,4S,5S,6R)-3,4,5-Trihydroxy-6-(Hydroxymethyl)Oxan-2-Yl]Oxy-3,4-Dihydroisochromen-1-One
IUPAC Name (3R)-3-(3-hydroxy-4-methoxyphenyl)-8-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,4-dihydroisochromen-1-one
Synonyms phyllodulcin 8-O-glucoside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL245484
PubChem CID 44440845
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 VCSSIMKISKEQEO-IUTJQLAGSA-N
Standard InCHI InChI=1S/C22H24O10/c1-29-13-6-5-10(7-12(13)24)15-8-11-3-2-4-14(17(11)21(28)30-15)31-22-20(27)19(26)18(25)16(9-23)32-22/h2-7,15-16,18-20,22-27H,8-9H2,1H3/t15-,16-,18-,19+,20-,22-/m1/s1
SMILES COc1ccc(cc1O)[C@H]1Cc2cccc(c2C(=O)O1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   448.14 Volume:   424.289
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Van der Waals volume.
Dense:   1.056 LogP:   0.476
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.104
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.565
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   155.14
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Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.396 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.993 Fsp3:   0.409
MCE-18:   86.29
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.583 Fluc inhibitor:   0.45
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.101
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.414
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.102 Promiscuous compounds:   0.306

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.137 MDCK Permeability:   -5.164
Pgp-inhibitor:   0.001 Pgp-substrate:   0.2
PAMPA:   0.949
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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):   0.075
20% Bioavailability (F20%):   0.07 30% Bioavailability (F30%):   0.963
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.016 MRP1:   0.493
Plasma Protein Binding (PPB):   81.656% Volume Distribution (VD):   -0.397
Fu: 16.922%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.072
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.008 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.987
HLM stability:   0.116
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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):  2.609 Half-life (T1/2):  3.651

ADMET: Toxicity

hERG Blockers:  0.032 hERG Blockers (10um):  0.16
Human Hepatotoxicity (H-HT):  0.615 Drug-induced Liver Injury (DILI):  0.94
AMES Toxicity:  0.899 Rat Oral Acute Toxicity:  0.012
Maximum Recommended Daily Dose:  0.064 Skin Sensitization:  0.999
Carcinogencity:  0.346 Eye Corrosion:  0.0
Eye Irritation:  0.506 Respiratory Toxicity:  0.004
Drug-induced Neurotoxicity:  0.014 Ototoxicity:  0.885
Hematotoxicity:  0.144 Drug-induced Nephrotoxicity:  0.77
Genotoxicity:  0.719 RPMI-8226 Immunitoxicity:  0.069
A549 Cytotoxicity:  0.167 Hek293 Cytotoxicity:  0.168
BCF:   0.402
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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:   3.081
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.579
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.743
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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
NPO9360.1 Hydrangea macrophylla var. thunbergii Varieties Hydrangeaceae Eukaryota Leaves n.a. n.a. PMID[17609121]
NPO9360.1 Hydrangea macrophylla var. thunbergii Varieties Hydrangeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9360.1 Hydrangea macrophylla var. thunbergii Varieties Hydrangeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9360.1 Hydrangea macrophylla var. thunbergii Varieties Hydrangeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]

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
NPT520 Cell line 3T3-L1 Mus musculus Activity = 3.6 % PMID[23395661]
NPT520 Cell line 3T3-L1 Mus musculus Activity = -1.5 % PMID[18625769]
NPT520 Cell line 3T3-L1 Mus musculus Activity = -3.0 % PubChem BioAssay data set
NPT520 Cell line 3T3-L1 Mus musculus Activity = 6.6 % PMID[20855744]
NPT520 Cell line 3T3-L1 Mus musculus Activity = 8.7 % PMID[18183025]

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 NPC298847 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
0.7857 Intermediate Similarity NPC328093
0.5357 Remote Similarity NPC5778
0.5301 Remote Similarity NPC279298
0.5125 Remote Similarity NPC189115
0.5068 Remote Similarity NPC310661
0.506 Remote Similarity NPC191046

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC298847 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