Natural Product: NPC525406

Natural Product IDNPC525406
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-hydroxy-3-(4-hydroxy-3-methoxy-phenyl)-7-[(2~{S},3~{S},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name 5-hydroxy-3-(4-hydroxy-3-methoxy-phenyl)-7-[(2~{S},3~{S},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 APCIHDWWOMFADS-QAGBHRCTSA-N
Standard InCHI InChI=1S/C22H22O11/c1-30-14-4-9(2-3-12(14)24)11-8-31-15-6-10(5-13(25)17(15)18(11)26)32-22-21(29)20(28)19(27)16(7-23)33-22/h2-6,8,16,19-25,27-29H,7H2,1H3/t16-,19-,20+,21+,22-/m1/s1
SMILES COC1=CC(C2=COC3=CC(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]4O)=CC(O)=C3C2=O)=CC=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   462.12 Volume:   430.443
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Van der Waals volume.
Dense:   1.074 LogP:   0.429
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.116
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.239
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   179.28
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.302 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.902 Fsp3:   0.318
MCE-18:   86.966
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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:   0.585 Fluc inhibitor:   0.296
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.945
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.857
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.104 Promiscuous compounds:   0.414

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.204 MDCK Permeability:   -5.381
Pgp-inhibitor:   0.0 Pgp-substrate:   0.803
PAMPA:   0.998
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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):   0.989
20% Bioavailability (F20%):   0.942 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.513
Plasma Protein Binding (PPB):   79.935% Volume Distribution (VD):   -0.137
Fu: 19.79%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.36
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.519 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.875 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.013 CYP2D6-substrate:   0.018
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.857
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.452
HLM stability:   0.011
?
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):  3.138 Half-life (T1/2):  3.213

ADMET: Toxicity

hERG Blockers:  0.023 hERG Blockers (10um):  0.102
Human Hepatotoxicity (H-HT):  0.674 Drug-induced Liver Injury (DILI):  0.983
AMES Toxicity:  0.961 Rat Oral Acute Toxicity:  0.119
Maximum Recommended Daily Dose:  0.089 Skin Sensitization:  0.997
Carcinogencity:  0.47 Eye Corrosion:  0.0
Eye Irritation:  0.313 Respiratory Toxicity:  0.19
Drug-induced Neurotoxicity:  0.023 Ototoxicity:  0.856
Hematotoxicity:  0.549 Drug-induced Nephrotoxicity:  0.857
Genotoxicity:  0.854 RPMI-8226 Immunitoxicity:  0.212
A549 Cytotoxicity:  0.836 Hek293 Cytotoxicity:  0.497
BCF:   0.387
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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:   2.985
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.427
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.6
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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
NPO2342 Cytisus scoparius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10667 Thermopsis rhombifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO53943 Thermopsis macrophylla Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2342 Cytisus scoparius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2342 Cytisus scoparius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2342 Cytisus scoparius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2342 Cytisus scoparius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10667 Thermopsis rhombifolia 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 NPC525406 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
0.8133 Intermediate Similarity NPC197896
0.8133 Intermediate Similarity NPC313163
0.7975 Intermediate Similarity NPC48773
0.7792 Intermediate Similarity NPC73511
0.775 Intermediate Similarity NPC479407
0.7215 Intermediate Similarity NPC234739
0.716 Intermediate Similarity NPC80140
0.6944 Remote Similarity NPC114192
0.6897 Remote Similarity NPC479405
0.6875 Remote Similarity NPC348541
0.6818 Remote Similarity NPC479404
0.6627 Remote Similarity NPC205076
0.6588 Remote Similarity NPC311830
0.6548 Remote Similarity NPC224462
0.6543 Remote Similarity NPC160515
0.6429 Remote Similarity NPC100720
0.6395 Remote Similarity NPC307518
0.6279 Remote Similarity NPC229729
0.619 Remote Similarity NPC105511
0.619 Remote Similarity NPC161749
0.619 Remote Similarity NPC156457
0.6163 Remote Similarity NPC481043
0.6136 Remote Similarity NPC601586
0.6129 Remote Similarity NPC479403
0.6092 Remote Similarity NPC601144
0.6 Remote Similarity NPC487212
0.5978 Remote Similarity NPC303913
0.5952 Remote Similarity NPC45165
0.5909 Remote Similarity NPC22832
0.5862 Remote Similarity NPC138540
0.5814 Remote Similarity NPC95090
0.5814 Remote Similarity NPC27408
0.5795 Remote Similarity NPC479402
0.5773 Remote Similarity NPC231194
0.5765 Remote Similarity NPC135345
0.5747 Remote Similarity NPC84362
0.573 Remote Similarity NPC243930
0.573 Remote Similarity NPC486578
0.5667 Remote Similarity NPC479406
0.5632 Remote Similarity NPC258035
0.5618 Remote Similarity NPC285197
0.561 Remote Similarity NPC191154
0.5556 Remote Similarity NPC601607
0.5556 Remote Similarity NPC610187
0.5526 Remote Similarity NPC303644
0.5517 Remote Similarity NPC289667
0.5517 Remote Similarity NPC39360
0.5517 Remote Similarity NPC29763
0.5517 Remote Similarity NPC210003
0.5495 Remote Similarity NPC607201
0.5495 Remote Similarity NPC607707
0.5455 Remote Similarity NPC297987
0.5455 Remote Similarity NPC487213
0.5455 Remote Similarity NPC277205
0.5455 Remote Similarity NPC37919
0.5455 Remote Similarity NPC136042
0.5455 Remote Similarity NPC323593
0.5455 Remote Similarity NPC203500
0.5455 Remote Similarity NPC189142
0.5455 Remote Similarity NPC77660
0.5444 Remote Similarity NPC479401
0.5443 Remote Similarity NPC254702
0.5443 Remote Similarity NPC473045
0.5393 Remote Similarity NPC22195
0.5393 Remote Similarity NPC21190
0.5357 Remote Similarity NPC134819
0.5333 Remote Similarity NPC60966
0.5326 Remote Similarity NPC602805
0.5319 Remote Similarity NPC251417
0.5275 Remote Similarity NPC307938
0.5269 Remote Similarity NPC203050
0.5269 Remote Similarity NPC469931
0.5269 Remote Similarity NPC488072
0.5269 Remote Similarity NPC225434
0.5217 Remote Similarity NPC101026
0.5217 Remote Similarity NPC488077
0.5195 Remote Similarity NPC116632
0.5169 Remote Similarity NPC259070
0.5169 Remote Similarity NPC261866
0.5169 Remote Similarity NPC211014
0.5161 Remote Similarity NPC116458
0.5161 Remote Similarity NPC246943
0.5161 Remote Similarity NPC605784
0.5149 Remote Similarity NPC195257
0.5111 Remote Similarity NPC603782
0.5055 Remote Similarity NPC125755
0.5046 Remote Similarity NPC295625

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC525406 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 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