Natural Product: NPC541685

Natural Product IDNPC541685
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6-methoxy-3-(4-methoxyphenyl)-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 6-methoxy-3-(4-methoxyphenyl)-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 YLYJXNTZVUEFJZ-LFDQFFAPSA-N
Standard InCHI InChI=1S/C23H24O10/c1-29-12-5-3-11(4-6-12)14-10-31-15-8-17(16(30-2)7-13(15)19(14)25)32-23-22(28)21(27)20(26)18(9-24)33-23/h3-8,10,18,20-24,26-28H,9H2,1-2H3/t18-,20-,21+,22+,23-/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)=C(OC)C=C3C2=O)C=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   460.14 Volume:   438.949
?
Van der Waals volume.
Dense:   1.048 LogP:   1.034
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.61
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.865
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   24.0
TPSA:   148.05
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.413 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.661 Fsp3:   0.348
MCE-18:   83.065
?
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:   0.57 Fluc inhibitor:   0.431
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.898
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.647
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.115 Promiscuous compounds:   0.355

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.922 MDCK Permeability:   -5.171
Pgp-inhibitor:   0.001 Pgp-substrate:   0.49
PAMPA:   0.988
?
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):   0.999
20% Bioavailability (F20%):   0.911 30% Bioavailability (F30%):   0.994
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.432
Plasma Protein Binding (PPB):   81.513% Volume Distribution (VD):   0.026
Fu: 20.294%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.319
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.663 CYP1A2-substrate:   0.012
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.07
CYP2C9-inhibitor:   0.776 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.042 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.944
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.029
?
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):  2.947 Half-life (T1/2):  3.015

ADMET: Toxicity

hERG Blockers:  0.05 hERG Blockers (10um):  0.103
Human Hepatotoxicity (H-HT):  0.701 Drug-induced Liver Injury (DILI):  0.982
AMES Toxicity:  0.957 Rat Oral Acute Toxicity:  0.1
Maximum Recommended Daily Dose:  0.128 Skin Sensitization:  0.99
Carcinogencity:  0.652 Eye Corrosion:  0.0
Eye Irritation:  0.192 Respiratory Toxicity:  0.149
Drug-induced Neurotoxicity:  0.206 Ototoxicity:  0.888
Hematotoxicity:  0.778 Drug-induced Nephrotoxicity:  0.897
Genotoxicity:  0.71 RPMI-8226 Immunitoxicity:  0.227
A549 Cytotoxicity:  0.749 Hek293 Cytotoxicity:  0.474
BCF:   0.475
?
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:   3.259
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.717
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.954
?
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]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1104/pp.84.1.73]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443709050069]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[12232319]
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]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22208890]
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]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
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]
NPO16977 Centrosema pubescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56532 Wisteria spp. Genus Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
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]
NPO18321 Medicago sativa 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]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
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]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16977 Centrosema pubescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
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 NPC541685 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 NPC135345
0.8286 Intermediate Similarity NPC105511
0.8261 Intermediate Similarity NPC45165
0.7297 Intermediate Similarity NPC603782
0.6974 Remote Similarity NPC73511
0.6933 Remote Similarity NPC259070
0.6923 Remote Similarity NPC229729
0.6842 Remote Similarity NPC258035
0.6842 Remote Similarity NPC161749
0.6709 Remote Similarity NPC601607
0.6456 Remote Similarity NPC205076
0.642 Remote Similarity NPC307518
0.641 Remote Similarity NPC156457
0.6406 Remote Similarity NPC120924
0.64 Remote Similarity NPC25547
0.625 Remote Similarity NPC100720
0.6 Remote Similarity NPC197896
0.6 Remote Similarity NPC313163
0.5976 Remote Similarity NPC224462
0.5976 Remote Similarity NPC479402
0.5952 Remote Similarity NPC48773
0.5942 Remote Similarity NPC186507
0.5802 Remote Similarity NPC234739
0.5783 Remote Similarity NPC481043
0.5783 Remote Similarity NPC479401
0.5765 Remote Similarity NPC479407
0.5732 Remote Similarity NPC186807
0.5679 Remote Similarity NPC211014
0.5647 Remote Similarity NPC607201
0.5618 Remote Similarity NPC475155
0.5556 Remote Similarity NPC160515
0.5488 Remote Similarity NPC58053
0.5476 Remote Similarity NPC138540
0.5467 Remote Similarity NPC96294
0.5465 Remote Similarity NPC479406
0.5422 Remote Similarity NPC95090
0.5422 Remote Similarity NPC27408
0.5362 Remote Similarity NPC195919
0.5244 Remote Similarity NPC487214
0.5233 Remote Similarity NPC80140
0.5217 Remote Similarity NPC182428
0.5211 Remote Similarity NPC605229
0.52 Remote Similarity NPC604162
0.5172 Remote Similarity NPC43761
0.5146 Remote Similarity NPC473895
0.5139 Remote Similarity NPC474340
0.5139 Remote Similarity NPC603503
0.5116 Remote Similarity NPC182045
0.5114 Remote Similarity NPC607707
0.5111 Remote Similarity NPC487212
0.5109 Remote Similarity NPC479405
0.5068 Remote Similarity NPC121522
0.5057 Remote Similarity NPC609451
0.5054 Remote Similarity NPC479404
0.5053 Remote Similarity NPC51326
0.5052 Remote Similarity NPC235575

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC541685 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
0.6842 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