Natural Product: NPC495976

Natural Product IDNPC495976
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)-5-methoxy-7-[(2~{S},3~{S},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{S},3~{S},4~{S},5~{R})-3,4,5-trihydroxytetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name 2-(3,4-dihydroxyphenyl)-5-methoxy-7-[(2~{S},3~{S},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{S},3~{S},4~{S},5~{R})-3,4,5-trihydroxytetrahydropyran-2-yl]oxymethyl]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 USAYZSRSHJHFGH-IFOWKGOYSA-N
Standard InCHI InChI=1S/C27H30O15/c1-37-17-5-11(6-18-20(17)14(30)7-16(41-18)10-2-3-12(28)13(29)4-10)40-27-25(36)23(34)22(33)19(42-27)9-39-26-24(35)21(32)15(31)8-38-26/h2-7,15,19,21-29,31-36H,8-9H2,1H3/t15-,19-,21+,22-,23+,24+,25+,26+,27-/m1/s1
SMILES COC1=CC(O[C@@H]2O[C@H](CO[C@@H]3OC[C@@H](O)[C@H](O)[C@@H]3O)[C@@H](O)[C@H](O)[C@@H]2O)=CC2=C1C(=O)C=C(C1=CC=C(O)C(O)=C1)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   594.16 Volume:   543.527
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Van der Waals volume.
Dense:   1.093 LogP:   0.351
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.875
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.411
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   30.0
TPSA:   238.2
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Topological Polar Surface Area.
 H-Bond Acceptor:   15.0
H-Bond Donor:   8.0 Rings:   5.0
Heavy Atoms:   15.0

MedChem Properties

QED Drug-Likeness Score:   0.146 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.646 Fsp3:   0.444
MCE-18:   115.923
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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:   Accepted BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.649 Fluc inhibitor:   0.287
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.986
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.912
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.052 Promiscuous compounds:   0.32

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.302 MDCK Permeability:   -5.335
Pgp-inhibitor:   0.0 Pgp-substrate:   0.951
PAMPA:   0.999
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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):   0.988
20% Bioavailability (F20%):   0.999 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.904
Plasma Protein Binding (PPB):   77.964% Volume Distribution (VD):   -0.076
Fu: 19.488%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.298
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 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:   0.003
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.03
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.397
HLM stability:   0.002
?
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):  2.006 Half-life (T1/2):  3.688

ADMET: Toxicity

hERG Blockers:  0.009 hERG Blockers (10um):  0.059
Human Hepatotoxicity (H-HT):  0.47 Drug-induced Liver Injury (DILI):  0.966
AMES Toxicity:  0.976 Rat Oral Acute Toxicity:  0.021
Maximum Recommended Daily Dose:  0.096 Skin Sensitization:  1.0
Carcinogencity:  0.165 Eye Corrosion:  0.0
Eye Irritation:  0.422 Respiratory Toxicity:  0.018
Drug-induced Neurotoxicity:  0.003 Ototoxicity:  0.96
Hematotoxicity:  0.519 Drug-induced Nephrotoxicity:  0.663
Genotoxicity:  0.892 RPMI-8226 Immunitoxicity:  0.148
A549 Cytotoxicity:  0.975 Hek293 Cytotoxicity:  0.648
BCF:   0.431
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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:   3.082
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.664
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.831
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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
NPO23424 Dirca palustris Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[10579873]
NPO23424 Dirca palustris Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[26225905]
NPO23424 Dirca palustris Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23424 Dirca palustris 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 NPC495976 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
0.9125 High Similarity NPC473512
0.8659 High Similarity NPC129827
0.8415 Intermediate Similarity NPC473657
0.8023 Intermediate Similarity NPC475497
0.7976 Intermediate Similarity NPC295613
0.7674 Intermediate Similarity NPC15358
0.7614 Intermediate Similarity NPC284277
0.6848 Remote Similarity NPC475366
0.663 Remote Similarity NPC210073
0.6628 Remote Similarity NPC610763
0.6421 Remote Similarity NPC65711
0.6316 Remote Similarity NPC488074
0.617 Remote Similarity NPC301683
0.617 Remote Similarity NPC67326
0.6129 Remote Similarity NPC254540
0.6064 Remote Similarity NPC236191
0.6022 Remote Similarity NPC52353
0.6 Remote Similarity NPC44931
0.5978 Remote Similarity NPC293004
0.5895 Remote Similarity NPC51774
0.5859 Remote Similarity NPC209296
0.5773 Remote Similarity NPC22062
0.5773 Remote Similarity NPC473634
0.5773 Remote Similarity NPC138811
0.5729 Remote Similarity NPC471079
0.57 Remote Similarity NPC229409
0.567 Remote Similarity NPC67105
0.5556 Remote Similarity NPC204693
0.5545 Remote Similarity NPC51326
0.5532 Remote Similarity NPC284960
0.5521 Remote Similarity NPC172807
0.551 Remote Similarity NPC142996
0.5495 Remote Similarity NPC19709
0.549 Remote Similarity NPC488089
0.5446 Remote Similarity NPC470443
0.5437 Remote Similarity NPC231194
0.5435 Remote Similarity NPC168822
0.5435 Remote Similarity NPC189142
0.5435 Remote Similarity NPC77660
0.5417 Remote Similarity NPC190003
0.5392 Remote Similarity NPC473623
0.5392 Remote Similarity NPC483707
0.5385 Remote Similarity NPC101636
0.5376 Remote Similarity NPC45638
0.5347 Remote Similarity NPC488073
0.5347 Remote Similarity NPC126784
0.5347 Remote Similarity NPC241423
0.5326 Remote Similarity NPC110349
0.5319 Remote Similarity NPC182045
0.5319 Remote Similarity NPC201292
0.53 Remote Similarity NPC203259
0.53 Remote Similarity NPC33054
0.53 Remote Similarity NPC176740
0.53 Remote Similarity NPC471725
0.53 Remote Similarity NPC134532
0.53 Remote Similarity NPC156869
0.53 Remote Similarity NPC602582
0.5283 Remote Similarity NPC244875
0.5258 Remote Similarity NPC194483
0.5248 Remote Similarity NPC186816
0.5204 Remote Similarity NPC211594
0.5196 Remote Similarity NPC64051
0.5192 Remote Similarity NPC600130
0.5149 Remote Similarity NPC245059
0.5149 Remote Similarity NPC102028
0.5094 Remote Similarity NPC298171
0.5053 Remote Similarity NPC58716
0.505 Remote Similarity NPC275454
0.505 Remote Similarity NPC227508
0.5049 Remote Similarity NPC46202
0.5048 Remote Similarity NPC270675
0.5048 Remote Similarity NPC195685
0.5047 Remote Similarity NPC470446

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC495976 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
0.6979 Remote Similarity NPD7472 Pre-clinical
0.5859 Remote Similarity NPD7054 Phase 4
0.5437 Remote Similarity NPD7251 Phase 2
0.53 Remote Similarity NPD6797 Phase 2

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