Natural Product: NPC554394

Natural Product IDNPC554394
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[2-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-carboxylic acid
IUPAC Name (2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[2-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-carboxylic acid
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:0002934] Flavonoid O-glucuronides
              • [CHEMONTID:0003534] Flavonoid-7-O-glucuronides

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 OTACUXNJRHHKOW-WXRGLTTHSA-N
Standard InCHI InChI=1S/C21H18O10/c22-10-3-1-9(2-4-10)14-8-13(23)12-6-5-11(7-15(12)30-14)29-21-18(26)16(24)17(25)19(31-21)20(27)28/h1-8,16-19,21-22,24-26H,(H,27,28)/t16-,17-,18+,19+,21+/m0/s1
SMILES O=C(O)[C@@H]1O[C@@H](OC2=CC=C3C(=O)C=C(C4=CC=C(O)C=C4)OC3=C2)[C@H](O)[C@@H](O)[C@@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   430.09 Volume:   401.72
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Van der Waals volume.
Dense:   1.071 LogP:   0.579
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.145
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.256
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   25.0
TPSA:   166.89
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Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.392 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.714 Fsp3:   0.238
MCE-18:   84.615
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.465 Fluc inhibitor:   0.578
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.977
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.826
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.326 Promiscuous compounds:   0.17

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.327 MDCK Permeability:   -5.144
Pgp-inhibitor:   0.0 Pgp-substrate:   0.576
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):   0.184
20% Bioavailability (F20%):   0.509 30% Bioavailability (F30%):   0.725
50% Bioavailability (F50%):   0.911

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.962
Plasma Protein Binding (PPB):   82.203% Volume Distribution (VD):   -0.182
Fu: 14.556%
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The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.471
OATP1B3 inhibitor:   0.91 BCRP inhibitor:   0.037
BSEP inhibitor:   0.009

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.438 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.009
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.065
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.755
HLM stability:   0.017
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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):  2.183 Half-life (T1/2):  3.209

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.054
Human Hepatotoxicity (H-HT):  0.498 Drug-induced Liver Injury (DILI):  0.984
AMES Toxicity:  0.709 Rat Oral Acute Toxicity:  0.117
Maximum Recommended Daily Dose:  0.26 Skin Sensitization:  0.821
Carcinogencity:  0.171 Eye Corrosion:  0.0
Eye Irritation:  0.849 Respiratory Toxicity:  0.168
Drug-induced Neurotoxicity:  0.029 Ototoxicity:  0.5
Hematotoxicity:  0.193 Drug-induced Nephrotoxicity:  0.747
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.098
A549 Cytotoxicity:  0.273 Hek293 Cytotoxicity:  0.41
BCF:   0.319
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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:   3.019
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.278
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.566
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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
NPO19044 Medicago polymorpha Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19044 Medicago polymorpha 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 NPC554394 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
0.7662 Intermediate Similarity NPC282169
0.7125 Intermediate Similarity NPC43211
0.679 Remote Similarity NPC20505
0.6707 Remote Similarity NPC608742
0.6585 Remote Similarity NPC210094
0.619 Remote Similarity NPC237435
0.6056 Remote Similarity NPC250266
0.6024 Remote Similarity NPC168822
0.5909 Remote Similarity NPC600989
0.5814 Remote Similarity NPC135277
0.5747 Remote Similarity NPC115760
0.5698 Remote Similarity NPC101191
0.5568 Remote Similarity NPC610187
0.5455 Remote Similarity NPC235260
0.5455 Remote Similarity NPC155763
0.5393 Remote Similarity NPC264735
0.5368 Remote Similarity NPC64051
0.5111 Remote Similarity NPC49344
0.5057 Remote Similarity NPC331652
0.5056 Remote Similarity NPC610763
0.505 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 NPC554394 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
0.619 Remote Similarity NPD4338 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