Natural Product: NPC517748

Natural Product IDNPC517748
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 20633-86-7
IUPAC Name 2-(4-hydroxyphenyl)-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-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 QUUXGUXWWVHPPP-YMQHIKHWSA-N
Standard InCHI InChI=1S/C21H20O9/c22-9-17-18(25)19(26)20(27)21(30-17)28-12-5-6-13-14(24)8-15(29-16(13)7-12)10-1-3-11(23)4-2-10/h1-8,17-23,25-27H,9H2/t17-,18-,19+,20-,21-/m1/s1
SMILES O=C1C=C(C2=CC=C(O)C=C2)OC2=CC(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)=CC=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.11 Volume:   395.567
?
Van der Waals volume.
Dense:   1.052 LogP:   1.081
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.525
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.481
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   149.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.406 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.64 Fsp3:   0.286
MCE-18:   80.889
?
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:   0.629 Fluc inhibitor:   0.554
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.982
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.762
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.312 Promiscuous compounds:   0.372

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.309 MDCK Permeability:   -5.038
Pgp-inhibitor:   0.0 Pgp-substrate:   0.28
PAMPA:   0.995
?
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):   0.39
20% Bioavailability (F20%):   0.398 30% Bioavailability (F30%):   0.973
50% Bioavailability (F50%):   0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.433
Plasma Protein Binding (PPB):   85.12% Volume Distribution (VD):   -0.095
Fu: 13.942%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.363
BSEP inhibitor:   0.031

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:   0.001 CYP2D6-substrate:   0.036
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.017
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.599
HLM stability:   0.005
?
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):  3.21 Half-life (T1/2):  3.663

ADMET: Toxicity

hERG Blockers:  0.036 hERG Blockers (10um):  0.101
Human Hepatotoxicity (H-HT):  0.679 Drug-induced Liver Injury (DILI):  0.969
AMES Toxicity:  0.918 Rat Oral Acute Toxicity:  0.046
Maximum Recommended Daily Dose:  0.14 Skin Sensitization:  0.973
Carcinogencity:  0.538 Eye Corrosion:  0.0
Eye Irritation:  0.507 Respiratory Toxicity:  0.032
Drug-induced Neurotoxicity:  0.013 Ototoxicity:  0.744
Hematotoxicity:  0.232 Drug-induced Nephrotoxicity:  0.518
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.085
A549 Cytotoxicity:  0.251 Hek293 Cytotoxicity:  0.628
BCF:   0.515
?
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:   3.199
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.562
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.768
?
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
NPO27666 Sophora tetraptera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27666 Sophora tetraptera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27666 Sophora tetraptera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27666 Sophora tetraptera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27666 Sophora tetraptera 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 NPC517748 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
0.8696 High Similarity NPC168822
0.7534 Intermediate Similarity NPC39360
0.7534 Intermediate Similarity NPC29763
0.7534 Intermediate Similarity NPC210003
0.7333 Intermediate Similarity NPC610763
0.72 Intermediate Similarity NPC93337
0.7105 Intermediate Similarity NPC105025
0.6974 Remote Similarity NPC146792
0.6842 Remote Similarity NPC83283
0.6753 Remote Similarity NPC161749
0.6623 Remote Similarity NPC58053
0.6538 Remote Similarity NPC95090
0.6538 Remote Similarity NPC27408
0.6538 Remote Similarity NPC189142
0.6538 Remote Similarity NPC77660
0.6456 Remote Similarity NPC186807
0.6418 Remote Similarity NPC250266
0.641 Remote Similarity NPC143851
0.6329 Remote Similarity NPC259152
0.6282 Remote Similarity NPC331652
0.625 Remote Similarity NPC45638
0.622 Remote Similarity NPC601144
0.6203 Remote Similarity NPC261866
0.6173 Remote Similarity NPC27942
0.6173 Remote Similarity NPC201292
0.6145 Remote Similarity NPC311830
0.6125 Remote Similarity NPC297987
0.6125 Remote Similarity NPC323593
0.6125 Remote Similarity NPC203500
0.6049 Remote Similarity NPC58716
0.6024 Remote Similarity NPC22832
0.6024 Remote Similarity NPC243930
0.6 Remote Similarity NPC45618
0.5952 Remote Similarity NPC602805
0.5952 Remote Similarity NPC607707
0.5904 Remote Similarity NPC609451
0.5854 Remote Similarity NPC24043
0.5833 Remote Similarity NPC284960
0.5833 Remote Similarity NPC601710
0.5833 Remote Similarity NPC605067
0.5783 Remote Similarity NPC182045
0.5765 Remote Similarity NPC116458
0.5765 Remote Similarity NPC246943
0.5747 Remote Similarity NPC472607
0.5714 Remote Similarity NPC191306
0.5679 Remote Similarity NPC45165
0.5663 Remote Similarity NPC84265
0.5647 Remote Similarity NPC229729
0.5632 Remote Similarity NPC172807
0.561 Remote Similarity NPC110349
0.561 Remote Similarity NPC77672
0.561 Remote Similarity NPC133671
0.561 Remote Similarity NPC135391
0.561 Remote Similarity NPC211014
0.561 Remote Similarity NPC78263
0.561 Remote Similarity NPC250069
0.5581 Remote Similarity NPC88023
0.5581 Remote Similarity NPC309025
0.5556 Remote Similarity NPC65003
0.5542 Remote Similarity NPC277205
0.5542 Remote Similarity NPC37919
0.5542 Remote Similarity NPC136042
0.5506 Remote Similarity NPC603300
0.5476 Remote Similarity NPC84362
0.5476 Remote Similarity NPC488080
0.5476 Remote Similarity NPC169977
0.5455 Remote Similarity NPC600870
0.5444 Remote Similarity NPC44931
0.5435 Remote Similarity NPC64425
0.5435 Remote Similarity NPC64051
0.5422 Remote Similarity NPC289667
0.5422 Remote Similarity NPC19709
0.5412 Remote Similarity NPC222936
0.5385 Remote Similarity NPC473512
0.5385 Remote Similarity NPC129827
0.5385 Remote Similarity NPC607513
0.5357 Remote Similarity NPC8573
0.5357 Remote Similarity NPC197896
0.5357 Remote Similarity NPC105511
0.5357 Remote Similarity NPC258035
0.5357 Remote Similarity NPC313163
0.5349 Remote Similarity NPC307938
0.5333 Remote Similarity NPC103409
0.5312 Remote Similarity NPC298171
0.5294 Remote Similarity NPC181712
0.5287 Remote Similarity NPC601607
0.5263 Remote Similarity NPC270675
0.5263 Remote Similarity NPC195685
0.5233 Remote Similarity NPC198324
0.5233 Remote Similarity NPC100720
0.5233 Remote Similarity NPC117260
0.5227 Remote Similarity NPC206123
0.5227 Remote Similarity NPC605784
0.5222 Remote Similarity NPC8856
0.5176 Remote Similarity NPC145038
0.5176 Remote Similarity NPC56077
0.5176 Remote Similarity NPC281131
0.5176 Remote Similarity NPC64305
0.5176 Remote Similarity NPC253662
0.5176 Remote Similarity NPC179950
0.5176 Remote Similarity NPC88789
0.5176 Remote Similarity NPC491374
0.5176 Remote Similarity NPC609879
0.5172 Remote Similarity NPC168584
0.5172 Remote Similarity NPC285197
0.5172 Remote Similarity NPC488071
0.5169 Remote Similarity NPC190003
0.5169 Remote Similarity NPC601586
0.5158 Remote Similarity NPC150767
0.5155 Remote Similarity NPC101636
0.5125 Remote Similarity NPC191154
0.5116 Remote Similarity NPC245014
0.5114 Remote Similarity NPC486578
0.5102 Remote Similarity NPC472994
0.5075 Remote Similarity NPC142319
0.5059 Remote Similarity NPC249281
0.5059 Remote Similarity NPC108831
0.5059 Remote Similarity NPC182634
0.5057 Remote Similarity NPC472459
0.5057 Remote Similarity NPC205076
0.5057 Remote Similarity NPC599850
0.5054 Remote Similarity NPC3583

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC517748 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
0.6753 Remote Similarity NPD4381 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