Natural Product: NPC298317

Natural Product IDNPC298317
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1R,2S,5R,6S)-2-(3,4-Methylenedioxyphenyl)-6-(4-Hydroxy-3,5-Dimethoxyphenyl)-3,7-Dioxabicyclo[3.3.0]Octane
IUPAC Name 4-[(3S,3aR,6S,6aR)-3-(1,3-benzodioxol-5-yl)-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]furan-6-yl]-2,6-dimethoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL225119
PubChem CID 16215278
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid 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 WQXZSCSXVJCPOG-BMHXQBNDSA-N
Standard InCHI InChI=1S/C21H22O7/c1-23-17-6-12(7-18(24-2)19(17)22)21-14-9-25-20(13(14)8-26-21)11-3-4-15-16(5-11)28-10-27-15/h3-7,13-14,20-22H,8-10H2,1-2H3/t13-,14-,20+,21+/m0/s1
SMILES COc1cc(cc(c1O)OC)[C@H]1OC[C@H]2[C@@H]1CO[C@@H]2c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.14 Volume:   374.703
?
Van der Waals volume.
Dense:   1.031 LogP:   1.556
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.964
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.367
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   25.0
TPSA:   75.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.865 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.788 Fsp3:   0.429
MCE-18:   90.133
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.434 Fluc inhibitor:   0.702
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.033
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.065
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.226 Promiscuous compounds:   0.324

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.452 MDCK Permeability:   -4.988
Pgp-inhibitor:   0.656 Pgp-substrate:   0.033
PAMPA:   0.002
?
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%):   0.009 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.439

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.831 MRP1:   0.954
Plasma Protein Binding (PPB):   93.363% Volume Distribution (VD):   -0.356
Fu: 5.804%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   0.97 BCRP inhibitor:   0.285
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.982
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.272
CYP2C9-inhibitor:   0.884 CYP2C9-substrate:   0.994
CYP2D6-inhibitor:   0.955 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.827 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.019
HLM stability:   0.652
?
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):  5.92 Half-life (T1/2):  2.059

ADMET: Toxicity

hERG Blockers:  0.115 hERG Blockers (10um):  0.406
Human Hepatotoxicity (H-HT):  0.767 Drug-induced Liver Injury (DILI):  0.945
AMES Toxicity:  0.769 Rat Oral Acute Toxicity:  0.339
Maximum Recommended Daily Dose:  0.422 Skin Sensitization:  0.829
Carcinogencity:  0.781 Eye Corrosion:  0.016
Eye Irritation:  0.938 Respiratory Toxicity:  0.437
Drug-induced Neurotoxicity:  0.457 Ototoxicity:  0.283
Hematotoxicity:  0.454 Drug-induced Nephrotoxicity:  0.51
Genotoxicity:  0.793 RPMI-8226 Immunitoxicity:  0.191
A549 Cytotoxicity:  0.291 Hek293 Cytotoxicity:  0.402
BCF:   1.41
?
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:   3.781
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.45
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.656
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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
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[16499322]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[17358082]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[17547458]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17040 Peperomia duclouxii Species Piperaceae 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
NPT1374 Cell line WI-38 Homo sapiens IC50 > 100.0 ug.mL-1 PMID[18257532]
NPT1475 Cell line WI-38 VA13 Homo sapiens IC50 > 100.0 ug.mL-1 PMID[25337628]
NPT65 Cell line HepG2 Homo sapiens IC50 > 100.0 ug.mL-1 PMID[14987052]

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 NPC298317 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 NPC255566
0.8077 Intermediate Similarity NPC88640
0.8077 Intermediate Similarity NPC101153
0.8077 Intermediate Similarity NPC193666
0.8077 Intermediate Similarity NPC123526
0.8077 Intermediate Similarity NPC608725
0.78 Intermediate Similarity NPC185071
0.7755 Intermediate Similarity NPC189474
0.7708 Intermediate Similarity NPC227160
0.7708 Intermediate Similarity NPC82111
0.7609 Intermediate Similarity NPC171928
0.7609 Intermediate Similarity NPC158526
0.7609 Intermediate Similarity NPC129687
0.7609 Intermediate Similarity NPC33611
0.7609 Intermediate Similarity NPC16830
0.7609 Intermediate Similarity NPC100223
0.6957 Remote Similarity NPC141765
0.6957 Remote Similarity NPC34103
0.6939 Remote Similarity NPC165155
0.6939 Remote Similarity NPC24490
0.6538 Remote Similarity NPC126409
0.6538 Remote Similarity NPC99572
0.6481 Remote Similarity NPC27843
0.6481 Remote Similarity NPC7171
0.6415 Remote Similarity NPC479434
0.6379 Remote Similarity NPC477702
0.625 Remote Similarity NPC121783
0.625 Remote Similarity NPC34902
0.625 Remote Similarity NPC18449
0.6207 Remote Similarity NPC12728
0.6129 Remote Similarity NPC265154
0.6078 Remote Similarity NPC148893
0.6078 Remote Similarity NPC222127
0.6078 Remote Similarity NPC25333
0.6078 Remote Similarity NPC49235
0.6078 Remote Similarity NPC82862
0.6034 Remote Similarity NPC474139
0.6034 Remote Similarity NPC483653
0.5965 Remote Similarity NPC469981
0.5893 Remote Similarity NPC14022
0.5893 Remote Similarity NPC601703
0.5862 Remote Similarity NPC142547
0.5862 Remote Similarity NPC228469
0.5781 Remote Similarity NPC487682
0.5769 Remote Similarity NPC115207
0.5769 Remote Similarity NPC158079
0.5769 Remote Similarity NPC228346
0.5769 Remote Similarity NPC40432
0.5769 Remote Similarity NPC161557
0.5741 Remote Similarity NPC158331
0.5735 Remote Similarity NPC114119
0.5735 Remote Similarity NPC286235
0.5735 Remote Similarity NPC471415
0.569 Remote Similarity NPC135777
0.566 Remote Similarity NPC606146
0.5556 Remote Similarity NPC600032
0.5538 Remote Similarity NPC212890
0.5536 Remote Similarity NPC27159
0.5536 Remote Similarity NPC186220
0.537 Remote Similarity NPC57119
0.537 Remote Similarity NPC158471
0.537 Remote Similarity NPC226862
0.5333 Remote Similarity NPC488984
0.5333 Remote Similarity NPC488985
0.5312 Remote Similarity NPC43514
0.5306 Remote Similarity NPC281864
0.5306 Remote Similarity NPC328682
0.5306 Remote Similarity NPC54321
0.5294 Remote Similarity NPC328567
0.5273 Remote Similarity NPC312199
0.5192 Remote Similarity NPC271208
0.5192 Remote Similarity NPC233224
0.5192 Remote Similarity NPC610263
0.5179 Remote Similarity NPC483654
0.5161 Remote Similarity NPC47181
0.5082 Remote Similarity NPC101807
0.5077 Remote Similarity NPC311057
0.5063 Remote Similarity NPC486097

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC298317 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