Natural Product: NPC110349

Natural Product IDNPC110349
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Lethedoside B
IUPAC Name 7-methoxy-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-(3,4,5-trimethoxyphenyl)chromen-4-one
Synonyms Lethedoside B
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL454823
PubChem CID 11756418
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides

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 DODIZDNNBLHXPJ-FGBFUVBKSA-N
Standard InCHI InChI=1S/C25H28O12/c1-31-12-7-15-20(16(8-12)36-25-23(30)22(29)21(28)19(10-26)37-25)13(27)9-14(35-15)11-5-17(32-2)24(34-4)18(6-11)33-3/h5-9,19,21-23,25-26,28-30H,10H2,1-4H3/t19-,21-,22+,23-,25-/m1/s1
SMILES OC[C@H]1O[C@@H](Oc2cc(OC)cc3c2c(=O)cc(o3)c2cc(OC)c(c(c2)OC)OC)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   520.16 Volume:   491.121
?
Van der Waals volume.
Dense:   1.059 LogP:   1.177
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.609
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.36
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   24.0
TPSA:   166.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.328 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.889 Fsp3:   0.4
MCE-18:   88.714
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.504 Fluc inhibitor:   0.137
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.864
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.778
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.089 Promiscuous compounds:   0.551

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.525 MDCK Permeability:   -5.011
Pgp-inhibitor:   0.064 Pgp-substrate:   0.11
PAMPA:   0.314
?
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):   0.43
20% Bioavailability (F20%):   0.041 30% Bioavailability (F30%):   0.611
50% Bioavailability (F50%):   0.97

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.514
Plasma Protein Binding (PPB):   86.931% Volume Distribution (VD):   -0.072
Fu: 14.322%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.994
BSEP inhibitor:   0.847

ADMET: Metabolism

CYP1A2-inhibitor:   0.552 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.161 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.047 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.016 CYP2D6-substrate:   0.921
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.965
HLM stability:   0.133
?
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):  2.836 Half-life (T1/2):  3.322

ADMET: Toxicity

hERG Blockers:  0.037 hERG Blockers (10um):  0.13
Human Hepatotoxicity (H-HT):  0.65 Drug-induced Liver Injury (DILI):  0.967
AMES Toxicity:  0.837 Rat Oral Acute Toxicity:  0.044
Maximum Recommended Daily Dose:  0.083 Skin Sensitization:  0.983
Carcinogencity:  0.536 Eye Corrosion:  0.0
Eye Irritation:  0.309 Respiratory Toxicity:  0.052
Drug-induced Neurotoxicity:  0.033 Ototoxicity:  0.836
Hematotoxicity:  0.451 Drug-induced Nephrotoxicity:  0.539
Genotoxicity:  0.42 RPMI-8226 Immunitoxicity:  0.132
A549 Cytotoxicity:  0.213 Hek293 Cytotoxicity:  0.323
BCF:   0.506
?
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:   3.091
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.513
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.731
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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
NPO33004 lethedon tannaensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[10075750]
NPO33004 lethedon tannaensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[8759170]

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
NPT91 Cell line KB Homo sapiens IC50 = 37.0 ug.mL-1 PMID[18070958]

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 NPC110349 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
0.8451 Intermediate Similarity NPC182045
0.8219 Intermediate Similarity NPC284960
0.7333 Intermediate Similarity NPC610763
0.716 Intermediate Similarity NPC15358
0.6582 Remote Similarity NPC222936
0.6462 Remote Similarity NPC29536
0.622 Remote Similarity NPC243930
0.6203 Remote Similarity NPC58053
0.6145 Remote Similarity NPC607707
0.6136 Remote Similarity NPC284277
0.6098 Remote Similarity NPC609451
0.6049 Remote Similarity NPC186807
0.6 Remote Similarity NPC83283
0.5926 Remote Similarity NPC93337
0.5926 Remote Similarity NPC95090
0.5926 Remote Similarity NPC27408
0.5862 Remote Similarity NPC295613
0.5854 Remote Similarity NPC105025
0.5854 Remote Similarity NPC45638
0.5783 Remote Similarity NPC201292
0.5778 Remote Similarity NPC475366
0.5778 Remote Similarity NPC475497
0.5765 Remote Similarity NPC311830
0.5765 Remote Similarity NPC602805
0.573 Remote Similarity NPC129827
0.5647 Remote Similarity NPC22832
0.5647 Remote Similarity NPC605067
0.561 Remote Similarity NPC261866
0.561 Remote Similarity NPC39360
0.561 Remote Similarity NPC29763
0.561 Remote Similarity NPC210003
0.5581 Remote Similarity NPC88023
0.5581 Remote Similarity NPC309025
0.5542 Remote Similarity NPC168822
0.5542 Remote Similarity NPC189142
0.5542 Remote Similarity NPC77660
0.5506 Remote Similarity NPC473657
0.5488 Remote Similarity NPC183357
0.5465 Remote Similarity NPC601144
0.5385 Remote Similarity NPC473512
0.5278 Remote Similarity NPC70853
0.5238 Remote Similarity NPC45618
0.5238 Remote Similarity NPC143851
0.5217 Remote Similarity NPC302408
0.5176 Remote Similarity NPC146792
0.5116 Remote Similarity NPC58716
0.5116 Remote Similarity NPC603655
0.5111 Remote Similarity NPC600870
0.5109 Remote Similarity NPC602523
0.5075 Remote Similarity NPC276195
0.5057 Remote Similarity NPC100720
0.5057 Remote Similarity NPC117260

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC110349 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
NPD

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