Natural Product: NPC576329

Natural Product IDNPC576329
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-[5-hydroxy-2-(3-hydroxy-4-methoxy-phenyl)-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-[5-hydroxy-2-(3-hydroxy-4-methoxy-phenyl)-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]

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 XCKMDTYMOHXUHG-UDGWLPKNSA-N
Standard InCHI InChI=1S/C22H20O12/c1-31-13-3-2-8(4-10(13)23)14-7-12(25)16-11(24)5-9(6-15(16)33-14)32-22-19(28)17(26)18(27)20(34-22)21(29)30/h2-7,17-20,22-24,26-28H,1H3,(H,29,30)/t17-,18-,19+,20+,22+/m0/s1
SMILES COC1=CC=C(C2=CC(=O)C3=C(O)C=C(O[C@@H]4O[C@@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]4O)C=C3O2)C=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   476.1 Volume:   436.597
?
Van der Waals volume.
Dense:   1.09 LogP:   1.271
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.5
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.785
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   25.0
TPSA:   196.35
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.292 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.952 Fsp3:   0.273
MCE-18:   90.643
?
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:   0
Colloidal aggregators:   0.451 Fluc inhibitor:   0.36
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.965
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.907
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.111 Promiscuous compounds:   0.39

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.163 MDCK Permeability:   -5.375
Pgp-inhibitor:   0.0 Pgp-substrate:   0.597
PAMPA:   1.0
?
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):   0.341
20% Bioavailability (F20%):   0.142 30% Bioavailability (F30%):   0.506
50% Bioavailability (F50%):   0.976

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.979
Plasma Protein Binding (PPB):   79.425% Volume Distribution (VD):   -0.309
Fu: 17.092%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.168
OATP1B3 inhibitor:   0.899 BCRP inhibitor:   0.169
BSEP inhibitor:   0.003

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.01 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.012
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.545
HLM stability:   0.059
?
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):  1.214 Half-life (T1/2):  4.063

ADMET: Toxicity

hERG Blockers:  0.014 hERG Blockers (10um):  0.087
Human Hepatotoxicity (H-HT):  0.408 Drug-induced Liver Injury (DILI):  0.974
AMES Toxicity:  0.799 Rat Oral Acute Toxicity:  0.081
Maximum Recommended Daily Dose:  0.073 Skin Sensitization:  0.967
Carcinogencity:  0.127 Eye Corrosion:  0.0
Eye Irritation:  0.736 Respiratory Toxicity:  0.056
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.579
Hematotoxicity:  0.124 Drug-induced Nephrotoxicity:  0.574
Genotoxicity:  0.938 RPMI-8226 Immunitoxicity:  0.093
A549 Cytotoxicity:  0.04 Hek293 Cytotoxicity:  0.132
BCF:   0.215
?
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:   2.814
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.249
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.38
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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
NPO20772 Pedalium murex Species Pedaliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20772 Pedalium murex Species Pedaliaceae 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 NPC576329 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
0.8684 High Similarity NPC608742
0.8312 Intermediate Similarity NPC20505
0.7848 Intermediate Similarity NPC282169
0.747 Intermediate Similarity NPC600989
0.6905 Remote Similarity NPC22832
0.6486 Remote Similarity NPC223579
0.6395 Remote Similarity NPC237435
0.6354 Remote Similarity NPC253685
0.6322 Remote Similarity NPC43211
0.6207 Remote Similarity NPC135277
0.6105 Remote Similarity NPC209296
0.6064 Remote Similarity NPC46202
0.5955 Remote Similarity NPC115760
0.5938 Remote Similarity NPC229409
0.5909 Remote Similarity NPC101191
0.5862 Remote Similarity NPC95090
0.5862 Remote Similarity NPC27408
0.5843 Remote Similarity NPC210094
0.5795 Remote Similarity NPC181712
0.5778 Remote Similarity NPC610187
0.5747 Remote Similarity NPC19709
0.5682 Remote Similarity NPC189142
0.5682 Remote Similarity NPC77660
0.5604 Remote Similarity NPC243930
0.5567 Remote Similarity NPC64051
0.5543 Remote Similarity NPC311830
0.5495 Remote Similarity NPC611303
0.5484 Remote Similarity NPC190003
0.5455 Remote Similarity NPC473043
0.5435 Remote Similarity NPC601144
0.5385 Remote Similarity NPC108406
0.5385 Remote Similarity NPC27942
0.5376 Remote Similarity NPC607707
0.5347 Remote Similarity NPC479765
0.5325 Remote Similarity NPC29353
0.5316 Remote Similarity NPC212678
0.5281 Remote Similarity NPC331652
0.5269 Remote Similarity NPC605067
0.525 Remote Similarity NPC177298
0.5248 Remote Similarity NPC479766
0.5222 Remote Similarity NPC261866
0.5222 Remote Similarity NPC39360
0.5222 Remote Similarity NPC29763
0.5222 Remote Similarity NPC210003
0.5208 Remote Similarity NPC606546
0.5204 Remote Similarity NPC22062
0.5204 Remote Similarity NPC473634
0.5204 Remote Similarity NPC138811
0.5161 Remote Similarity NPC235260
0.5161 Remote Similarity NPC49344
0.5161 Remote Similarity NPC155763
0.5106 Remote Similarity NPC264735
0.5106 Remote Similarity NPC486578
0.5063 Remote Similarity NPC48479
0.5062 Remote Similarity NPC160951
0.5062 Remote Similarity NPC195202
0.5062 Remote Similarity NPC52005
0.5054 Remote Similarity NPC138927
0.5053 Remote Similarity NPC220169
0.5052 Remote Similarity NPC8856
0.5051 Remote Similarity NPC210073
0.5045 Remote Similarity NPC198199
0.5044 Remote Similarity NPC120952

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC576329 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
0.6395 Remote Similarity NPD4338 Clinical (unspecified phase)
0.6105 Remote Similarity NPD7054 Phase 4

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