Natural Product: NPC573661

Natural Product IDNPC573661
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-[(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-[(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 IVCZEZUJCMWBBR-QGLKVJOYSA-N
Standard InCHI InChI=1S/C21H20O10/c22-8-17-18(26)19(27)20(28)21(31-17)29-10-2-3-11-13(24)7-15(30-16(11)6-10)9-1-4-12(23)14(25)5-9/h1-7,17-23,25-28H,8H2/t17-,18+,19-,20+,21+/m0/s1
SMILES O=C1C=C(C2=CC=C(O)C(O)=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:   432.11 Volume:   404.357
?
Van der Waals volume.
Dense:   1.069 LogP:   0.776
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.284
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.2
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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:   0.31 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.765 Fsp3:   0.286
MCE-18:   84.259
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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:   1 PAINS Alert:   1
Colloidal aggregators:   0.694 Fluc inhibitor:   0.48
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.997
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.834
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.337 Promiscuous compounds:   0.393

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.355 MDCK Permeability:   -5.153
Pgp-inhibitor:   0.0 Pgp-substrate:   0.12
PAMPA:   0.999
?
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):   0.397
20% Bioavailability (F20%):   0.946 30% Bioavailability (F30%):   0.985
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.889
Plasma Protein Binding (PPB):   82.255% Volume Distribution (VD):   -0.081
Fu: 16.561%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.789
BSEP inhibitor:   0.073

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:   0.002
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.215
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.626
HLM stability:   0.001
?
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):  3.324 Half-life (T1/2):  3.64

ADMET: Toxicity

hERG Blockers:  0.024 hERG Blockers (10um):  0.234
Human Hepatotoxicity (H-HT):  0.543 Drug-induced Liver Injury (DILI):  0.954
AMES Toxicity:  0.87 Rat Oral Acute Toxicity:  0.069
Maximum Recommended Daily Dose:  0.113 Skin Sensitization:  0.983
Carcinogencity:  0.279 Eye Corrosion:  0.0
Eye Irritation:  0.683 Respiratory Toxicity:  0.017
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.865
Hematotoxicity:  0.122 Drug-induced Nephrotoxicity:  0.331
Genotoxicity:  0.991 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.372 Hek293 Cytotoxicity:  0.233
BCF:   0.586
?
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:   3.278
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.838
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.131
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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
NPO19488 Trifolium subterraneum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17613 Sophora microphylla Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19488 Trifolium subterraneum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19488 Trifolium subterraneum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19488 Trifolium subterraneum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17613 Sophora microphylla 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 NPC573661 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 NPC168822
0.7568 Intermediate Similarity NPC189142
0.7568 Intermediate Similarity NPC77660
0.7237 Intermediate Similarity NPC45638
0.7143 Intermediate Similarity NPC201292
0.7013 Intermediate Similarity NPC58716
0.6582 Remote Similarity NPC610763
0.6538 Remote Similarity NPC39360
0.6538 Remote Similarity NPC29763
0.6538 Remote Similarity NPC210003
0.6341 Remote Similarity NPC22832
0.6329 Remote Similarity NPC58053
0.6329 Remote Similarity NPC19709
0.625 Remote Similarity NPC93337
0.625 Remote Similarity NPC95090
0.625 Remote Similarity NPC277205
0.625 Remote Similarity NPC27408
0.625 Remote Similarity NPC37919
0.625 Remote Similarity NPC136042
0.6207 Remote Similarity NPC607513
0.6173 Remote Similarity NPC186807
0.6173 Remote Similarity NPC84362
0.6173 Remote Similarity NPC105025
0.6145 Remote Similarity NPC601144
0.6145 Remote Similarity NPC605067
0.6125 Remote Similarity NPC261866
0.6071 Remote Similarity NPC311830
0.6049 Remote Similarity NPC161749
0.6049 Remote Similarity NPC146792
0.6047 Remote Similarity NPC8856
0.6 Remote Similarity NPC190003
0.5952 Remote Similarity NPC243930
0.5952 Remote Similarity NPC284960
0.5934 Remote Similarity NPC150767
0.5926 Remote Similarity NPC83283
0.5926 Remote Similarity NPC143851
0.5904 Remote Similarity NPC117260
0.5882 Remote Similarity NPC602805
0.5882 Remote Similarity NPC605784
0.5882 Remote Similarity NPC607707
0.5843 Remote Similarity NPC3583
0.5833 Remote Similarity NPC191306
0.5833 Remote Similarity NPC488071
0.5833 Remote Similarity NPC609451
0.5783 Remote Similarity NPC245014
0.5765 Remote Similarity NPC229729
0.5732 Remote Similarity NPC45618
0.5714 Remote Similarity NPC182045
0.5682 Remote Similarity NPC254540
0.5663 Remote Similarity NPC145038
0.5663 Remote Similarity NPC56077
0.5663 Remote Similarity NPC297987
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
0.5663 Remote Similarity NPC609879
0.561 Remote Similarity NPC45165
0.5604 Remote Similarity NPC115674
0.5581 Remote Similarity NPC601710
0.5542 Remote Similarity NPC289667
0.5542 Remote Similarity NPC110349
0.5529 Remote Similarity NPC42773
0.5529 Remote Similarity NPC45522
0.5529 Remote Similarity NPC599850
0.5495 Remote Similarity NPC210073
0.5484 Remote Similarity NPC65711
0.5476 Remote Similarity NPC282987
0.5476 Remote Similarity NPC323593
0.5476 Remote Similarity NPC203500
0.5476 Remote Similarity NPC259152
0.5426 Remote Similarity NPC229409
0.5422 Remote Similarity NPC473043
0.5422 Remote Similarity NPC331652
0.5417 Remote Similarity NPC250266
0.5393 Remote Similarity NPC600870
0.5349 Remote Similarity NPC27942
0.5341 Remote Similarity NPC88023
0.5341 Remote Similarity NPC116458
0.5341 Remote Similarity NPC246943
0.5341 Remote Similarity NPC309025
0.5333 Remote Similarity NPC606546
0.5287 Remote Similarity NPC285197
0.5275 Remote Similarity NPC603300
0.5263 Remote Similarity NPC103409
0.5233 Remote Similarity NPC24043
0.5227 Remote Similarity NPC486578
0.5227 Remote Similarity NPC601607
0.5176 Remote Similarity NPC77672
0.5176 Remote Similarity NPC133671
0.5176 Remote Similarity NPC135391
0.5176 Remote Similarity NPC78263
0.5176 Remote Similarity NPC250069
0.5176 Remote Similarity NPC238376
0.5172 Remote Similarity NPC222936
0.5116 Remote Similarity NPC64305
0.5116 Remote Similarity NPC258035
0.5114 Remote Similarity NPC20505
0.5111 Remote Similarity NPC601586
0.5062 Remote Similarity NPC191154
0.5057 Remote Similarity NPC84265
0.5057 Remote Similarity NPC271692
0.5057 Remote Similarity NPC181712
0.5056 Remote Similarity NPC21666
0.5053 Remote Similarity NPC64425
0.5051 Remote Similarity NPC484301
0.5051 Remote Similarity NPC253685

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC573661 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
0.6049 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