Natural Product: NPC573804

Natural Product IDNPC573804
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-(3-hydroxy-4-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 3-(3-hydroxy-4-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 WACBUPFEGWUGPB-MBMVPVEPSA-N
Standard InCHI InChI=1S/C22H22O10/c1-29-15-5-2-10(6-14(15)24)13-9-30-16-7-11(3-4-12(16)18(13)25)31-22-21(28)20(27)19(26)17(8-23)32-22/h2-7,9,17,19-24,26-28H,8H2,1H3/t17-,19-,20+,21+,22-/m1/s1
SMILES COC1=CC=C(C2=COC3=CC(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]4O)=CC=C3C2=O)C=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   446.12 Volume:   421.653
?
Van der Waals volume.
Dense:   1.058 LogP:   0.215
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.019
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.744
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   159.05
?
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:   0.37 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.748 Fsp3:   0.318
MCE-18:   83.621
?
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:   0
Colloidal aggregators:   0.554 Fluc inhibitor:   0.547
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.961
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.81
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.144 Promiscuous compounds:   0.283

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.159 MDCK Permeability:   -5.345
Pgp-inhibitor:   0.0 Pgp-substrate:   0.423
PAMPA:   0.994
?
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):   0.995
20% Bioavailability (F20%):   0.778 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.405
Plasma Protein Binding (PPB):   75.723% Volume Distribution (VD):   -0.166
Fu: 24.303%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.129
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.627 CYP1A2-substrate:   0.014
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.876 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.797
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.993
HLM stability:   0.009
?
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):  2.474 Half-life (T1/2):  3.334

ADMET: Toxicity

hERG Blockers:  0.042 hERG Blockers (10um):  0.115
Human Hepatotoxicity (H-HT):  0.748 Drug-induced Liver Injury (DILI):  0.972
AMES Toxicity:  0.967 Rat Oral Acute Toxicity:  0.123
Maximum Recommended Daily Dose:  0.104 Skin Sensitization:  0.995
Carcinogencity:  0.575 Eye Corrosion:  0.0
Eye Irritation:  0.396 Respiratory Toxicity:  0.19
Drug-induced Neurotoxicity:  0.07 Ototoxicity:  0.881
Hematotoxicity:  0.669 Drug-induced Nephrotoxicity:  0.892
Genotoxicity:  0.698 RPMI-8226 Immunitoxicity:  0.241
A549 Cytotoxicity:  0.797 Hek293 Cytotoxicity:  0.474
BCF:   0.354
?
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:   3.085
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.406
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.629
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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
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s40502-015-0143-x]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1093/pcp/pcg054]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443709050069]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Leaves n.a. n.a. PMID[12713396]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota roots n.a. n.a. PMID[20022509]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21866899]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23325115]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Roots n.a. n.a. PMID[23541646]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28140583]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[39683057]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[7381508]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15413 Glycyrrhiza pallidiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
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]
NPO15413 Glycyrrhiza pallidiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15413 Glycyrrhiza pallidiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18578 Baptisia spp. Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28766 Thermopsis spp. Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15413 Glycyrrhiza pallidiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15413 Glycyrrhiza pallidiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29384 Glycyrrhiza glabra 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 NPC573804 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 NPC229729
0.8333 Intermediate Similarity NPC45165
0.7867 Intermediate Similarity NPC161749
0.7595 Intermediate Similarity NPC307518
0.7326 Intermediate Similarity NPC51326
0.7273 Intermediate Similarity NPC235575
0.725 Intermediate Similarity NPC601607
0.6923 Remote Similarity NPC135345
0.6753 Remote Similarity NPC25547
0.675 Remote Similarity NPC258035
0.6667 Remote Similarity NPC73511
0.6625 Remote Similarity NPC211014
0.6543 Remote Similarity NPC105511
0.6341 Remote Similarity NPC603782
0.631 Remote Similarity NPC224462
0.6279 Remote Similarity NPC479407
0.619 Remote Similarity NPC100720
0.6092 Remote Similarity NPC48773
0.6064 Remote Similarity NPC231194
0.6 Remote Similarity NPC205076
0.5977 Remote Similarity NPC607201
0.5952 Remote Similarity NPC197896
0.5952 Remote Similarity NPC313163
0.5952 Remote Similarity NPC156457
0.593 Remote Similarity NPC479402
0.5862 Remote Similarity NPC22832
0.5795 Remote Similarity NPC150442
0.5765 Remote Similarity NPC168822
0.5765 Remote Similarity NPC234739
0.5618 Remote Similarity NPC479406
0.5595 Remote Similarity NPC487214
0.5568 Remote Similarity NPC479401
0.5506 Remote Similarity NPC43761
0.5506 Remote Similarity NPC21666
0.5506 Remote Similarity NPC486578
0.5506 Remote Similarity NPC605067
0.5465 Remote Similarity NPC259070
0.5455 Remote Similarity NPC80710
0.5395 Remote Similarity NPC181209
0.5393 Remote Similarity NPC481043
0.5393 Remote Similarity NPC80140
0.5349 Remote Similarity NPC160515
0.5287 Remote Similarity NPC58053
0.5283 Remote Similarity NPC76047
0.5281 Remote Similarity NPC138540
0.5263 Remote Similarity NPC181124
0.5256 Remote Similarity NPC25292
0.5227 Remote Similarity NPC95090
0.5227 Remote Similarity NPC27408
0.5222 Remote Similarity NPC285197
0.5205 Remote Similarity NPC182428
0.519 Remote Similarity NPC103409
0.5169 Remote Similarity NPC186807
0.5165 Remote Similarity NPC120099
0.5128 Remote Similarity NPC139293
0.5104 Remote Similarity NPC479405
0.5052 Remote Similarity NPC479404

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC573804 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
0.7867 Intermediate Similarity NPD4381 Clinical (unspecified phase)
0.5349 Remote Similarity NPD3818 Discontinued

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