Natural Product: NPC496523

Natural Product IDNPC496523
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-(3,4-dihydroxyphenyl)-7-methoxy-5-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name 2-(3,4-dihydroxyphenyl)-7-methoxy-5-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic 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 ZXVSQQSRCKKYLS-AOIWZFSPSA-N
Standard InCHI InChI=1S/C22H22O11/c1-30-10-5-15-18(13(26)7-14(31-15)9-2-3-11(24)12(25)4-9)16(6-10)32-22-21(29)20(28)19(27)17(8-23)33-22/h2-7,17,19-25,27-29H,8H2,1H3/t17-,19+,20-,21+,22+/m0/s1
SMILES COC1=CC(O[C@@H]2O[C@@H](CO)[C@@H](O)[C@H](O)[C@H]2O)=C2C(=O)C=C(C3=CC=C(O)C(O)=C3)OC2=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   462.12 Volume:   430.443
?
Van der Waals volume.
Dense:   1.074 LogP:   1.076
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.608
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.169
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   179.28
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.282 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.885 Fsp3:   0.318
MCE-18:   86.966
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MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.683 Fluc inhibitor:   0.296
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.99
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.875
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.104 Promiscuous compounds:   0.39

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.299 MDCK Permeability:   -5.289
Pgp-inhibitor:   0.0 Pgp-substrate:   0.071
PAMPA:   0.991
?
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):   0.355
20% Bioavailability (F20%):   0.908 30% Bioavailability (F30%):   0.98
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.669
Plasma Protein Binding (PPB):   82.052% Volume Distribution (VD):   -0.068
Fu: 18.371%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.827
BSEP inhibitor:   0.067

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.465
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.958
HLM stability:   0.023
?
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):  3.652 Half-life (T1/2):  3.315

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.31
Human Hepatotoxicity (H-HT):  0.521 Drug-induced Liver Injury (DILI):  0.938
AMES Toxicity:  0.817 Rat Oral Acute Toxicity:  0.077
Maximum Recommended Daily Dose:  0.133 Skin Sensitization:  0.991
Carcinogencity:  0.286 Eye Corrosion:  0.0
Eye Irritation:  0.702 Respiratory Toxicity:  0.028
Drug-induced Neurotoxicity:  0.003 Ototoxicity:  0.879
Hematotoxicity:  0.094 Drug-induced Nephrotoxicity:  0.201
Genotoxicity:  0.855 RPMI-8226 Immunitoxicity:  0.036
A549 Cytotoxicity:  0.384 Hek293 Cytotoxicity:  0.196
BCF:   0.566
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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:   3.276
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.866
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.085
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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
NPO4718 Daphne sericea Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4718 Daphne sericea Species Thymelaeaceae 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 NPC496523 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
0.8472 Intermediate Similarity NPC610763
0.7895 Intermediate Similarity NPC284960
0.7703 Intermediate Similarity NPC110349
0.7632 Intermediate Similarity NPC182045
0.7368 Intermediate Similarity NPC168822
0.7368 Intermediate Similarity NPC189142
0.7368 Intermediate Similarity NPC77660
0.7273 Intermediate Similarity NPC45638
0.7179 Intermediate Similarity NPC201292
0.6835 Remote Similarity NPC58716
0.6795 Remote Similarity NPC83283
0.6437 Remote Similarity NPC129827
0.642 Remote Similarity NPC84362
0.6386 Remote Similarity NPC22832
0.6375 Remote Similarity NPC39360
0.6375 Remote Similarity NPC29763
0.6375 Remote Similarity NPC210003
0.6341 Remote Similarity NPC222936
0.631 Remote Similarity NPC311830
0.6296 Remote Similarity NPC93337
0.6296 Remote Similarity NPC95090
0.6296 Remote Similarity NPC27408
0.625 Remote Similarity NPC473512
0.622 Remote Similarity NPC105025
0.6173 Remote Similarity NPC58053
0.6173 Remote Similarity NPC19709
0.6145 Remote Similarity NPC599850
0.6098 Remote Similarity NPC277205
0.6098 Remote Similarity NPC37919
0.6098 Remote Similarity NPC136042
0.6098 Remote Similarity NPC609879
0.6071 Remote Similarity NPC169404
0.6071 Remote Similarity NPC176186
0.6067 Remote Similarity NPC607513
0.6024 Remote Similarity NPC186807
0.6 Remote Similarity NPC243930
0.6 Remote Similarity NPC601144
0.6 Remote Similarity NPC605067
0.5976 Remote Similarity NPC261866
0.5952 Remote Similarity NPC117260
0.593 Remote Similarity NPC602805
0.593 Remote Similarity NPC607707
0.5909 Remote Similarity NPC8856
0.5904 Remote Similarity NPC146792
0.5882 Remote Similarity NPC488071
0.5854 Remote Similarity NPC183357
0.5843 Remote Similarity NPC295613
0.5806 Remote Similarity NPC150767
0.5765 Remote Similarity NPC42773
0.5765 Remote Similarity NPC100720
0.5765 Remote Similarity NPC45522
0.5747 Remote Similarity NPC605784
0.5714 Remote Similarity NPC3583
0.5698 Remote Similarity NPC609451
0.5682 Remote Similarity NPC190003
0.5667 Remote Similarity NPC473657
0.5647 Remote Similarity NPC245014
0.5604 Remote Similarity NPC15358
0.5595 Remote Similarity NPC45618
0.5595 Remote Similarity NPC143851
0.5591 Remote Similarity NPC284277
0.5568 Remote Similarity NPC479406
0.5556 Remote Similarity NPC254540
0.5529 Remote Similarity NPC145038
0.5529 Remote Similarity NPC56077
0.5529 Remote Similarity NPC297987
0.5529 Remote Similarity NPC281131
0.5529 Remote Similarity NPC253662
0.5529 Remote Similarity NPC179950
0.5529 Remote Similarity NPC88789
0.5529 Remote Similarity NPC259152
0.5529 Remote Similarity NPC491374
0.5517 Remote Similarity NPC191306
0.5517 Remote Similarity NPC479402
0.5506 Remote Similarity NPC479407
0.5484 Remote Similarity NPC115674
0.5455 Remote Similarity NPC601710
0.5426 Remote Similarity NPC475366
0.5426 Remote Similarity NPC475497
0.5405 Remote Similarity NPC604569
0.5393 Remote Similarity NPC150442
0.5393 Remote Similarity NPC88023
0.5393 Remote Similarity NPC309025
0.5376 Remote Similarity NPC210073
0.5368 Remote Similarity NPC65711
0.5349 Remote Similarity NPC282987
0.5349 Remote Similarity NPC323593
0.5349 Remote Similarity NPC203500
0.5333 Remote Similarity NPC601586
0.5294 Remote Similarity NPC473043
0.5294 Remote Similarity NPC331652
0.5287 Remote Similarity NPC22195
0.5287 Remote Similarity NPC24043
0.5287 Remote Similarity NPC271692
0.5287 Remote Similarity NPC21190
0.5281 Remote Similarity NPC486578
0.5233 Remote Similarity NPC289667
0.5227 Remote Similarity NPC27942
0.5222 Remote Similarity NPC116458
0.5222 Remote Similarity NPC246943
0.5217 Remote Similarity NPC606546
0.52 Remote Similarity NPC244875
0.52 Remote Similarity NPC605047
0.5161 Remote Similarity NPC480466
0.5155 Remote Similarity NPC229409
0.5139 Remote Similarity NPC101294
0.5139 Remote Similarity NPC278556
0.5114 Remote Similarity NPC181712
0.5114 Remote Similarity NPC259905
0.5114 Remote Similarity NPC488080
0.5114 Remote Similarity NPC169977
0.5111 Remote Similarity NPC606560
0.5065 Remote Similarity NPC473044
0.5057 Remote Similarity NPC77672
0.5057 Remote Similarity NPC133671
0.5057 Remote Similarity NPC135391
0.5057 Remote Similarity NPC78263
0.5057 Remote Similarity NPC250069
0.5057 Remote Similarity NPC238376
0.5056 Remote Similarity NPC472459
0.5053 Remote Similarity NPC102028

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC496523 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
0.5612 Remote Similarity NPD7472 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