Natural Product: NPC176586

Natural Product IDNPC176586
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3S,4S)-4-(1,3-Benzodioxol-5-Ylmethyl)-3-[(3,4,5-Trimethoxyphenyl)Methyl]Oxolan-2-One
IUPAC Name (3S,4S)-4-(1,3-benzodioxol-5-ylmethyl)-3-[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2021357
PubChem CID 10476098
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003424] 9,9'-epoxylignans
            • [CHEMONTID:0001613] Dibenzylbutyrolactone lignans

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 GMLDZDDTZKXJLU-CVEARBPZSA-N
Standard InCHI InChI=1S/C22H24O7/c1-24-19-9-14(10-20(25-2)21(19)26-3)7-16-15(11-27-22(16)23)6-13-4-5-17-18(8-13)29-12-28-17/h4-5,8-10,15-16H,6-7,11-12H2,1-3H3/t15-,16+/m1/s1
SMILES COc1cc(C[C@H]2[C@H](Cc3ccc4c(c3)OCO4)COC2=O)cc(c1OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   400.15 Volume:   397.919
?
Van der Waals volume.
Dense:   1.006 LogP:   2.249
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.492
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.753
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   22.0
TPSA:   72.45
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.662 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.22 Fsp3:   0.409
MCE-18:   71.677
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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:   0.091 Fluc inhibitor:   0.409
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.029
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.367
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.268 Promiscuous compounds:   0.098

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.842 MDCK Permeability:   -4.724
Pgp-inhibitor:   0.582 Pgp-substrate:   0.025
PAMPA:   0.037
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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):   0.0
20% Bioavailability (F20%):   0.172 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.377

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.435 MRP1:   0.929
Plasma Protein Binding (PPB):   98.514% Volume Distribution (VD):   -0.309
Fu: 1.536%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.973
OATP1B3 inhibitor:   0.819 BCRP inhibitor:   0.002
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.017 CYP1A2-substrate:   0.941
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.177 CYP2C9-substrate:   0.792
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.583
?
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):  4.019 Half-life (T1/2):  1.28

ADMET: Toxicity

hERG Blockers:  0.352 hERG Blockers (10um):  0.63
Human Hepatotoxicity (H-HT):  0.939 Drug-induced Liver Injury (DILI):  0.99
AMES Toxicity:  0.649 Rat Oral Acute Toxicity:  0.608
Maximum Recommended Daily Dose:  0.632 Skin Sensitization:  0.943
Carcinogencity:  0.846 Eye Corrosion:  0.001
Eye Irritation:  0.578 Respiratory Toxicity:  0.503
Drug-induced Neurotoxicity:  0.938 Ototoxicity:  0.767
Hematotoxicity:  0.821 Drug-induced Nephrotoxicity:  0.944
Genotoxicity:  0.993 RPMI-8226 Immunitoxicity:  0.287
A549 Cytotoxicity:  0.442 Hek293 Cytotoxicity:  0.597
BCF:   1.67
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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:   4.216
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.916
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.122
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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
NPO28099 Epimedium cremeum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27987 Clavelina cylindrica Species Clavelinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28419 Tribolium confusum Species Tenebrionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28099 Epimedium cremeum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27987 Clavelina cylindrica Species Clavelinidae 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
NPT91 Cell line KB Homo sapiens ED50 = 5.2 ug ml-1 PMID[1992152]
NPT561 Organism Tetrahymena pyriformis Tetrahymena pyriformis MIC > 20.0 ug.mL-1 PMID[1992152]
NPT561 Organism Tetrahymena pyriformis Tetrahymena pyriformis MIC < 20.0 ug.mL-1 PMID[1992152]
NPT2254 Organism Schistosoma mansoni Schistosoma mansoni Activity > 75.0 % PMID[33479649]

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 NPC176586 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 NPC210354
0.9388 High Similarity NPC191158
0.9388 High Similarity NPC177644
0.8776 High Similarity NPC205915
0.8723 High Similarity NPC110958
0.8723 High Similarity NPC19890
0.8367 Intermediate Similarity NPC40237
0.8163 Intermediate Similarity NPC92693
0.8163 Intermediate Similarity NPC211386
0.8 Intermediate Similarity NPC145569
0.8 Intermediate Similarity NPC143895
0.766 Intermediate Similarity NPC72796
0.7414 Intermediate Similarity NPC282291
0.7414 Intermediate Similarity NPC166137
0.7347 Intermediate Similarity NPC223807
0.7255 Intermediate Similarity NPC192255
0.7018 Intermediate Similarity NPC293757
0.7018 Intermediate Similarity NPC668
0.7 Intermediate Similarity NPC216223
0.6949 Remote Similarity NPC56184
0.6923 Remote Similarity NPC474288
0.68 Remote Similarity NPC476748
0.6552 Remote Similarity NPC106920
0.6552 Remote Similarity NPC15811
0.6538 Remote Similarity NPC11453
0.6452 Remote Similarity NPC174512
0.6379 Remote Similarity NPC185908
0.6379 Remote Similarity NPC482891
0.6078 Remote Similarity NPC600801
0.6 Remote Similarity NPC5310
0.6 Remote Similarity NPC300776
0.6 Remote Similarity NPC176814
0.6 Remote Similarity NPC3982
0.6 Remote Similarity NPC4982
0.6 Remote Similarity NPC606629
0.5926 Remote Similarity NPC196937
0.5789 Remote Similarity NPC158737
0.5625 Remote Similarity NPC487679
0.5625 Remote Similarity NPC487678
0.5625 Remote Similarity NPC482889
0.5522 Remote Similarity NPC478705
0.5517 Remote Similarity NPC68779
0.5517 Remote Similarity NPC108598
0.541 Remote Similarity NPC273657
0.5397 Remote Similarity NPC80230
0.5397 Remote Similarity NPC104024
0.5397 Remote Similarity NPC101755
0.5397 Remote Similarity NPC304687
0.5397 Remote Similarity NPC65574
0.5385 Remote Similarity NPC76687
0.5345 Remote Similarity NPC171550
0.5345 Remote Similarity NPC134764
0.5283 Remote Similarity NPC344161
0.5224 Remote Similarity NPC136757
0.5217 Remote Similarity NPC478703
0.5217 Remote Similarity NPC478704
0.5098 Remote Similarity NPC80241
0.5098 Remote Similarity NPC301641
0.5098 Remote Similarity NPC485483
0.5079 Remote Similarity NPC230968
0.5079 Remote Similarity NPC102260
0.5077 Remote Similarity NPC262455
0.5077 Remote Similarity NPC177476
0.5077 Remote Similarity NPC474158
0.507 Remote Similarity NPC158635
0.507 Remote Similarity NPC229882

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC176586 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