Natural Product: NPC500046

Natural Product IDNPC500046
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-3-[(2~{S},3~{R},4~{S},5~{R},6~{S})-4,5-dihydroxy-6-methyl-3-[(2~{R},3~{S},4~{S},5~{S})-3,4,5-trihydroxytetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one
IUPAC Name 7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-3-[(2~{S},3~{R},4~{S},5~{R},6~{S})-4,5-dihydroxy-6-methyl-3-[(2~{R},3~{S},4~{S},5~{S})-3,4,5-trihydroxytetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides
            • [CHEMONTID:0003533] Flavonoid-7-O-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 GKVRQPHAMQILQC-ZCARKDDXSA-N
Standard InCHI InChI=1S/C43H56O24/c1-14(2)4-9-18-21(61-43-39(32(56)28(52)23(12-45)63-43)67-41-34(58)30(54)27(51)22(11-44)62-41)10-19(47)24-29(53)37(35(64-36(18)24)16-5-7-17(46)8-6-16)65-42-38(31(55)25(49)15(3)60-42)66-40-33(57)26(50)20(48)13-59-40/h4-8,10,15,20,22-23,25-28,30-34,38-52,54-58H,9,11-13H2,1-3H3/t15-,20-,22-,23+,25-,26-,27+,28+,30-,31-,32-,33-,34+,38+,39+,40+,41-,42-,43+/m0/s1
SMILES CC(C)=CCC1=C(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O[C@@H]2O[C@@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C(O)C2=C1OC(C1=CC=C(O)C=C1)=C(O[C@@H]1O[C@@H](C)[C@H](O)[C@H](O)[C@H]1O[C@H]1OC[C@H](O)[C@H](O)[C@@H]1O)C2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   956.32 Volume:   879.626
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Van der Waals volume.
Dense:   1.087 LogP:   0.174
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.146
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.2
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The logarithm of aqueous solubility value.
Rotatable Bonds:   13.0 Rigid Bonds:   43.0
TPSA:   387.27
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Topological Polar Surface Area.
 H-Bond Acceptor:   24.0
H-Bond Donor:   14.0 Rings:   7.0
Heavy Atoms:   24.0

MedChem Properties

QED Drug-Likeness Score:   0.073 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.097 Fsp3:   0.605
MCE-18:   182.565
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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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.673 Fluc inhibitor:   0.268
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.666
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.592
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.117 Promiscuous compounds:   0.169

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.95 MDCK Permeability:   -4.838
Pgp-inhibitor:   0.0 Pgp-substrate:   0.99
PAMPA:   1.0
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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):   0.999
20% Bioavailability (F20%):   0.942 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.05
Plasma Protein Binding (PPB):   69.169% Volume Distribution (VD):   -0.251
Fu: 30.294%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.017
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:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.973
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.983
?
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):  0.167 Half-life (T1/2):  4.996

ADMET: Toxicity

hERG Blockers:  0.001 hERG Blockers (10um):  0.025
Human Hepatotoxicity (H-HT):  0.819 Drug-induced Liver Injury (DILI):  0.992
AMES Toxicity:  0.977 Rat Oral Acute Toxicity:  0.004
Maximum Recommended Daily Dose:  0.0 Skin Sensitization:  1.0
Carcinogencity:  0.006 Eye Corrosion:  0.0
Eye Irritation:  0.001 Respiratory Toxicity:  0.0
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  0.999
Hematotoxicity:  0.292 Drug-induced Nephrotoxicity:  0.981
Genotoxicity:  0.971 RPMI-8226 Immunitoxicity:  0.263
A549 Cytotoxicity:  0.933 Hek293 Cytotoxicity:  0.631
BCF:   0.513
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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:   3.295
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.226
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.136
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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
NPO13357 Vancouveria hexandra Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13357 Vancouveria hexandra Species Berberidaceae 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 NPC500046 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
0.6346 Remote Similarity NPC304741
0.6204 Remote Similarity NPC5319
0.6111 Remote Similarity NPC35119
0.6075 Remote Similarity NPC240306
0.5963 Remote Similarity NPC32641
0.5963 Remote Similarity NPC256188
0.5946 Remote Similarity NPC292929
0.5943 Remote Similarity NPC163242
0.5943 Remote Similarity NPC272068
0.5865 Remote Similarity NPC170052
0.5865 Remote Similarity NPC135846
0.5833 Remote Similarity NPC255157
0.5833 Remote Similarity NPC259896
0.5776 Remote Similarity NPC25523
0.5752 Remote Similarity NPC602448
0.5714 Remote Similarity NPC76831
0.5688 Remote Similarity NPC470444
0.5664 Remote Similarity NPC221342
0.5664 Remote Similarity NPC476470
0.5648 Remote Similarity NPC470405
0.5607 Remote Similarity NPC473682
0.5566 Remote Similarity NPC476215
0.5556 Remote Similarity NPC219043
0.5487 Remote Similarity NPC142142
0.5455 Remote Similarity NPC155877
0.5424 Remote Similarity NPC48984
0.537 Remote Similarity NPC254855
0.537 Remote Similarity NPC94610
0.5357 Remote Similarity NPC64425
0.531 Remote Similarity NPC12013
0.531 Remote Similarity NPC11432
0.531 Remote Similarity NPC477613
0.5299 Remote Similarity NPC14187
0.5278 Remote Similarity NPC66087
0.525 Remote Similarity NPC480441
0.5238 Remote Similarity NPC192539
0.5238 Remote Similarity NPC480443
0.5179 Remote Similarity NPC65003
0.5172 Remote Similarity NPC220173
0.5124 Remote Similarity NPC164704
0.5091 Remote Similarity NPC95866
0.5083 Remote Similarity NPC488075

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC500046 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
0.6204 Remote Similarity NPD7804 Clinical (unspecified phase)

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