Natural Product: NPC583322

Natural Product IDNPC583322
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-(3,4-dihydroxyphenyl)-5-hydroxy-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 3-(3,4-dihydroxyphenyl)-5-hydroxy-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]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0000507] Isoflavonoid 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 WJHSRFQBVYHKKL-FZHKGVQDSA-N
Standard InCHI InChI=1S/C21H20O11/c22-6-15-18(27)19(28)20(29)21(32-15)31-9-4-13(25)16-14(5-9)30-7-10(17(16)26)8-1-2-11(23)12(24)3-8/h1-5,7,15,18-25,27-29H,6H2/t15-,18+,19-,20+,21+/m0/s1
SMILES O=C1C(C2=CC=C(O)C(O)=C2)=COC2=CC(O[C@@H]3O[C@@H](CO)[C@@H](O)[C@H](O)[C@H]3O)=CC(O)=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   448.1 Volume:   413.147
?
Van der Waals volume.
Dense:   1.085 LogP:   0.441
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.11
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.364
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   190.28
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   7.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.261 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.955 Fsp3:   0.286
MCE-18:   87.63
?
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:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.637 Fluc inhibitor:   0.301
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.974
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.799
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.288 Promiscuous compounds:   0.554

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.395 MDCK Permeability:   -5.088
Pgp-inhibitor:   0.0 Pgp-substrate:   0.256
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):   0.572
20% Bioavailability (F20%):   0.92 30% Bioavailability (F30%):   0.995
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.424
Plasma Protein Binding (PPB):   81.887% Volume Distribution (VD):   -0.194
Fu: 17.412%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.929
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.589
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 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:   0.178
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.04
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):  3.672 Half-life (T1/2):  3.32

ADMET: Toxicity

hERG Blockers:  0.028 hERG Blockers (10um):  0.313
Human Hepatotoxicity (H-HT):  0.569 Drug-induced Liver Injury (DILI):  0.97
AMES Toxicity:  0.843 Rat Oral Acute Toxicity:  0.083
Maximum Recommended Daily Dose:  0.06 Skin Sensitization:  0.99
Carcinogencity:  0.166 Eye Corrosion:  0.0
Eye Irritation:  0.466 Respiratory Toxicity:  0.014
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.95
Hematotoxicity:  0.083 Drug-induced Nephrotoxicity:  0.471
Genotoxicity:  0.929 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.476 Hek293 Cytotoxicity:  0.13
BCF:   0.522
?
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:   3.204
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.702
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.928
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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
NPO18578 Baptisia spp. Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28766 Thermopsis spp. Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42993 Lupinus spp. Genus Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO44865 Bryum capillare Species Bryaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO53828 Lupinus albus L. Genus Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO63501 Orobus tuberosus n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO7555 Sedum lineare Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18578 Baptisia spp. Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7555 Sedum lineare Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28766 Thermopsis spp. Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7555 Sedum lineare Species Crassulaceae 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 NPC583322 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
0.8714 High Similarity NPC197896
0.8714 High Similarity NPC313163
0.7838 Intermediate Similarity NPC73511
0.7703 Intermediate Similarity NPC234739
0.7632 Intermediate Similarity NPC80140
0.7333 Intermediate Similarity NPC348541
0.7317 Intermediate Similarity NPC479405
0.7229 Intermediate Similarity NPC479404
0.6974 Remote Similarity NPC160515
0.6625 Remote Similarity NPC205076
0.6582 Remote Similarity NPC161749
0.6582 Remote Similarity NPC156457
0.6477 Remote Similarity NPC479403
0.642 Remote Similarity NPC100720
0.6386 Remote Similarity NPC307518
0.6375 Remote Similarity NPC277205
0.6375 Remote Similarity NPC37919
0.6375 Remote Similarity NPC136042
0.6375 Remote Similarity NPC189142
0.6375 Remote Similarity NPC77660
0.6341 Remote Similarity NPC224462
0.6322 Remote Similarity NPC303913
0.631 Remote Similarity NPC48773
0.6296 Remote Similarity NPC84362
0.6265 Remote Similarity NPC229729
0.622 Remote Similarity NPC138540
0.6173 Remote Similarity NPC105511
0.6163 Remote Similarity NPC487212
0.6118 Remote Similarity NPC479407
0.6049 Remote Similarity NPC289667
0.6 Remote Similarity NPC605784
0.5976 Remote Similarity NPC297987
0.5976 Remote Similarity NPC258035
0.5974 Remote Similarity NPC191154
0.5952 Remote Similarity NPC481043
0.5926 Remote Similarity NPC45165
0.5882 Remote Similarity NPC610187
0.5854 Remote Similarity NPC39360
0.5854 Remote Similarity NPC29763
0.5854 Remote Similarity NPC210003
0.5783 Remote Similarity NPC95090
0.5783 Remote Similarity NPC27408
0.5783 Remote Similarity NPC323593
0.5783 Remote Similarity NPC203500
0.5765 Remote Similarity NPC479402
0.5765 Remote Similarity NPC285197
0.5732 Remote Similarity NPC135345
0.5698 Remote Similarity NPC22832
0.5696 Remote Similarity NPC134819
0.5663 Remote Similarity NPC261866
0.5632 Remote Similarity NPC116458
0.5632 Remote Similarity NPC479406
0.5632 Remote Similarity NPC246943
0.5595 Remote Similarity NPC487213
0.5581 Remote Similarity NPC307938
0.5517 Remote Similarity NPC243930
0.5517 Remote Similarity NPC486578
0.5517 Remote Similarity NPC601144
0.5517 Remote Similarity NPC601607
0.5484 Remote Similarity NPC64425
0.5479 Remote Similarity NPC303644
0.5476 Remote Similarity NPC211014
0.5455 Remote Similarity NPC311830
0.5444 Remote Similarity NPC8856
0.5444 Remote Similarity NPC251417
0.5402 Remote Similarity NPC169404
0.5402 Remote Similarity NPC176186
0.5402 Remote Similarity NPC479401
0.5294 Remote Similarity NPC19709
0.5294 Remote Similarity NPC238376
0.5287 Remote Similarity NPC60966
0.5281 Remote Similarity NPC607201
0.5281 Remote Similarity NPC607707
0.5253 Remote Similarity NPC14187
0.5233 Remote Similarity NPC168822
0.5222 Remote Similarity NPC601586
0.5208 Remote Similarity NPC35119
0.5196 Remote Similarity NPC480441
0.5195 Remote Similarity NPC114192
0.5172 Remote Similarity NPC22195
0.5172 Remote Similarity NPC245014
0.5172 Remote Similarity NPC58716
0.5172 Remote Similarity NPC21190
0.5135 Remote Similarity NPC116632
0.5132 Remote Similarity NPC473044
0.5116 Remote Similarity NPC259070
0.5057 Remote Similarity NPC145038
0.5057 Remote Similarity NPC56077
0.5057 Remote Similarity NPC281131
0.5057 Remote Similarity NPC253662
0.5057 Remote Similarity NPC179950
0.5057 Remote Similarity NPC88789
0.5057 Remote Similarity NPC491374
0.5057 Remote Similarity NPC603782
0.5057 Remote Similarity NPC609879
0.5053 Remote Similarity NPC115674
0.5052 Remote Similarity NPC32641
0.5052 Remote Similarity NPC256188
0.5049 Remote Similarity NPC470715
0.5049 Remote Similarity NPC164704

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC583322 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
0.6582 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