Natural Product: NPC546472

Natural Product IDNPC546472
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7-dihydroxy-3-[4-[(2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]chromen-4-one
IUPAC Name 5,7-dihydroxy-3-[4-[(2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]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 ISQRJFLLIDGZEP-KJRRRBQDSA-N
Standard InCHI InChI=1S/C21H20O10/c22-7-15-18(26)19(27)20(28)21(31-15)30-11-3-1-9(2-4-11)12-8-29-14-6-10(23)5-13(24)16(14)17(12)25/h1-6,8,15,18-24,26-28H,7H2/t15-,18-,19-,20+,21-/m0/s1
SMILES O=C1C(C2=CC=C(O[C@H]3O[C@@H](CO)[C@H](O)[C@H](O)[C@H]3O)C=C2)=COC2=CC(O)=CC(O)=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   432.11 Volume:   404.357
?
Van der Waals volume.
Dense:   1.069 LogP:   0.505
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.092
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.417
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   170.05
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.331 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.81 Fsp3:   0.286
MCE-18:   84.259
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.582 Fluc inhibitor:   0.326
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.869
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.695
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.283 Promiscuous compounds:   0.431

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.366 MDCK Permeability:   -5.198
Pgp-inhibitor:   0.0 Pgp-substrate:   0.666
PAMPA:   0.997
?
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):   0.698
20% Bioavailability (F20%):   0.701 30% Bioavailability (F30%):   0.987
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.108
Plasma Protein Binding (PPB):   92.198% Volume Distribution (VD):   -0.161
Fu: 5.888%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.909
OATP1B3 inhibitor:   0.981 BCRP inhibitor:   0.698
BSEP inhibitor:   0.018

ADMET: Metabolism

CYP1A2-inhibitor:   0.968 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.067 CYP2C9-substrate:   0.317
CYP2D6-inhibitor:   0.178 CYP2D6-substrate:   0.056
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.877
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.044
?
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):  2.102 Half-life (T1/2):  2.479

ADMET: Toxicity

hERG Blockers:  0.052 hERG Blockers (10um):  0.355
Human Hepatotoxicity (H-HT):  0.521 Drug-induced Liver Injury (DILI):  0.94
AMES Toxicity:  0.874 Rat Oral Acute Toxicity:  0.203
Maximum Recommended Daily Dose:  0.273 Skin Sensitization:  0.842
Carcinogencity:  0.315 Eye Corrosion:  0.0
Eye Irritation:  0.633 Respiratory Toxicity:  0.172
Drug-induced Neurotoxicity:  0.028 Ototoxicity:  0.825
Hematotoxicity:  0.122 Drug-induced Nephrotoxicity:  0.617
Genotoxicity:  0.932 RPMI-8226 Immunitoxicity:  0.127
A549 Cytotoxicity:  0.541 Hek293 Cytotoxicity:  0.479
BCF:   0.72
?
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:   3.406
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.683
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.029
?
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
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO62971 Styphnolobium japonicum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28939 Piptanthus nepalensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20846 Sophora japonica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24342 Lupinus albus Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28939 Piptanthus nepalensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20846 Sophora japonica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20846 Sophora japonica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28939 Piptanthus nepalensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28939 Piptanthus nepalensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24342 Lupinus albus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20846 Sophora japonica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20846 Sophora japonica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28939 Piptanthus nepalensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20846 Sophora japonica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24342 Lupinus albus Species Fabaceae 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 NPC546472 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
1.0 High Similarity NPC156457
0.8333 Intermediate Similarity NPC138540
0.7733 Intermediate Similarity NPC481043
0.7703 Intermediate Similarity NPC73511
0.7568 Intermediate Similarity NPC258035
0.7105 Intermediate Similarity NPC197896
0.7105 Intermediate Similarity NPC313163
0.6753 Remote Similarity NPC143851
0.6667 Remote Similarity NPC64305
0.6667 Remote Similarity NPC234739
0.6623 Remote Similarity NPC160515
0.65 Remote Similarity NPC205076
0.6486 Remote Similarity NPC78697
0.6471 Remote Similarity NPC294409
0.6471 Remote Similarity NPC490701
0.6456 Remote Similarity NPC161749
0.642 Remote Similarity NPC80140
0.641 Remote Similarity NPC45165
0.641 Remote Similarity NPC135345
0.6296 Remote Similarity NPC472459
0.6265 Remote Similarity NPC307518
0.622 Remote Similarity NPC479401
0.6098 Remote Similarity NPC100720
0.6049 Remote Similarity NPC105511
0.6049 Remote Similarity NPC603782
0.6023 Remote Similarity NPC479405
0.5955 Remote Similarity NPC479404
0.5952 Remote Similarity NPC229729
0.5926 Remote Similarity NPC348541
0.5904 Remote Similarity NPC21100
0.5862 Remote Similarity NPC487212
0.5833 Remote Similarity NPC191306
0.5833 Remote Similarity NPC60735
0.5833 Remote Similarity NPC224462
0.5833 Remote Similarity NPC26230
0.5814 Remote Similarity NPC48773
0.5765 Remote Similarity NPC120099
0.5765 Remote Similarity NPC609478
0.5732 Remote Similarity NPC77672
0.5732 Remote Similarity NPC133671
0.5732 Remote Similarity NPC135391
0.5732 Remote Similarity NPC78263
0.5732 Remote Similarity NPC250069
0.5698 Remote Similarity NPC88023
0.5698 Remote Similarity NPC309025
0.5663 Remote Similarity NPC145038
0.5663 Remote Similarity NPC56077
0.5663 Remote Similarity NPC281131
0.5663 Remote Similarity NPC253662
0.5663 Remote Similarity NPC179950
0.5663 Remote Similarity NPC88789
0.5663 Remote Similarity NPC491374
0.5647 Remote Similarity NPC479402
0.5625 Remote Similarity NPC25547
0.5616 Remote Similarity NPC200316
0.5581 Remote Similarity NPC601607
0.5542 Remote Similarity NPC112755
0.5542 Remote Similarity NPC19388
0.5542 Remote Similarity NPC170675
0.5542 Remote Similarity NPC240431
0.5542 Remote Similarity NPC55786
0.5541 Remote Similarity NPC194653
0.5517 Remote Similarity NPC136761
0.5517 Remote Similarity NPC479406
0.5484 Remote Similarity NPC479403
0.5474 Remote Similarity NPC76831
0.5455 Remote Similarity NPC479407
0.5402 Remote Similarity NPC197285
0.5402 Remote Similarity NPC601710
0.5395 Remote Similarity NPC104728
0.5362 Remote Similarity NPC39426
0.5362 Remote Similarity NPC608554
0.5357 Remote Similarity NPC289667
0.5357 Remote Similarity NPC211014
0.5349 Remote Similarity NPC325555
0.5349 Remote Similarity NPC226304
0.5333 Remote Similarity NPC279668
0.5333 Remote Similarity NPC278323
0.5316 Remote Similarity NPC268668
0.5294 Remote Similarity NPC487213
0.5281 Remote Similarity NPC203050
0.5281 Remote Similarity NPC225434
0.5258 Remote Similarity NPC287889
0.5233 Remote Similarity NPC100818
0.5205 Remote Similarity NPC78341
0.5176 Remote Similarity NPC58053
0.5176 Remote Similarity NPC254306
0.5169 Remote Similarity NPC607201
0.5161 Remote Similarity NPC303913
0.5116 Remote Similarity NPC95090
0.5116 Remote Similarity NPC27408
0.5098 Remote Similarity NPC470712
0.5065 Remote Similarity NPC254702
0.5065 Remote Similarity NPC142876
0.5062 Remote Similarity NPC233918
0.506 Remote Similarity NPC107838
0.5057 Remote Similarity NPC186807

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC546472 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
0.6456 Remote Similarity NPD4381 Clinical (unspecified phase)
0.5362 Remote Similarity NPD1510 Phase 2
0.5059 Remote Similarity NPD3818 Discontinued

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