Natural Product: NPC185071

Natural Product IDNPC185071
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1S,2R,5S,6R)-2-(5-Methoxy-3,4-Methylenedioxyphenyl)-6-(4-Hydroxy-3,5-Dimethoxyphenyl)-3,7-Dioxabicyclo[3.3.0]Octane
IUPAC Name 4-[(3R,3aS,6R,6aS)-3-(7-methoxy-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 CHEMBL222537
PubChem CID 16215277
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 PALWAHQHFKVAGQ-HANNOOJCSA-N
Standard InCHI InChI=1S/C22H24O8/c1-24-15-4-11(5-16(25-2)19(15)23)20-13-8-28-21(14(13)9-27-20)12-6-17(26-3)22-18(7-12)29-10-30-22/h4-7,13-14,20-21,23H,8-10H2,1-3H3/t13-,14-,20+,21+/m1/s1
SMILES COc1cc(cc(c1O)OC)[C@H]1[C@@H]2CO[C@@H](c3cc(c4c(c3)OCO4)OC)[C@@H]2CO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.15 Volume:   400.789
?
Van der Waals volume.
Dense:   1.038 LogP:   1.551
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.012
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.516
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   25.0
TPSA:   84.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.795 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.918 Fsp3:   0.455
MCE-18:   92.812
?
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:   0.388 Fluc inhibitor:   0.417
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.038
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.156
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.228 Promiscuous compounds:   0.668

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.324 MDCK Permeability:   -4.914
Pgp-inhibitor:   0.697 Pgp-substrate:   0.073
PAMPA:   0.003
?
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%):   0.353

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.759 MRP1:   0.966
Plasma Protein Binding (PPB):   89.637% Volume Distribution (VD):   -0.307
Fu: 8.018%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.986 BCRP inhibitor:   0.48
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.963
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.348
CYP2C9-inhibitor:   0.269 CYP2C9-substrate:   0.982
CYP2D6-inhibitor:   0.07 CYP2D6-substrate:   0.881
CYP3A4-inhibitor:   0.925 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.115
HLM stability:   0.111
?
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):  6.119 Half-life (T1/2):  2.102

ADMET: Toxicity

hERG Blockers:  0.11 hERG Blockers (10um):  0.426
Human Hepatotoxicity (H-HT):  0.793 Drug-induced Liver Injury (DILI):  0.948
AMES Toxicity:  0.675 Rat Oral Acute Toxicity:  0.353
Maximum Recommended Daily Dose:  0.527 Skin Sensitization:  0.775
Carcinogencity:  0.786 Eye Corrosion:  0.003
Eye Irritation:  0.833 Respiratory Toxicity:  0.419
Drug-induced Neurotoxicity:  0.515 Ototoxicity:  0.343
Hematotoxicity:  0.54 Drug-induced Nephrotoxicity:  0.55
Genotoxicity:  0.833 RPMI-8226 Immunitoxicity:  0.24
A549 Cytotoxicity:  0.329 Hek293 Cytotoxicity:  0.405
BCF:   1.64
?
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:   3.877
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.53
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.624
?
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 = 96.6 ug.mL-1 PMID[1331331]
NPT1475 Cell line WI-38 VA13 Homo sapiens IC50 > 100.0 ug.mL-1 PMID[18257532]
NPT65 Cell line HepG2 Homo sapiens IC50 > 100.0 ug.mL-1 PMID[18257532]

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 NPC185071 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
0.8182 Intermediate Similarity NPC165155
0.8182 Intermediate Similarity NPC24490
0.7955 Intermediate Similarity NPC148893
0.7955 Intermediate Similarity NPC25333
0.7955 Intermediate Similarity NPC49235
0.7843 Intermediate Similarity NPC12728
0.78 Intermediate Similarity NPC298317
0.78 Intermediate Similarity NPC255566
0.7442 Intermediate Similarity NPC141765
0.7442 Intermediate Similarity NPC34103
0.7358 Intermediate Similarity NPC477702
0.6471 Remote Similarity NPC189474
0.6364 Remote Similarity NPC281864
0.6364 Remote Similarity NPC328682
0.6364 Remote Similarity NPC54321
0.6333 Remote Similarity NPC212890
0.6275 Remote Similarity NPC126409
0.6275 Remote Similarity NPC99572
0.625 Remote Similarity NPC88640
0.625 Remote Similarity NPC101153
0.625 Remote Similarity NPC193666
0.625 Remote Similarity NPC123526
0.625 Remote Similarity NPC608725
0.6154 Remote Similarity NPC479434
0.5769 Remote Similarity NPC227160
0.5769 Remote Similarity NPC82111
0.5714 Remote Similarity NPC473092
0.5714 Remote Similarity NPC473093
0.5714 Remote Similarity NPC8050
0.5625 Remote Similarity NPC216129
0.5625 Remote Similarity NPC130449
0.5625 Remote Similarity NPC248132
0.56 Remote Similarity NPC204215
0.56 Remote Similarity NPC171928
0.56 Remote Similarity NPC158526
0.56 Remote Similarity NPC129687
0.56 Remote Similarity NPC33611
0.56 Remote Similarity NPC16830
0.56 Remote Similarity NPC100223
0.5556 Remote Similarity NPC27159
0.5556 Remote Similarity NPC186220
0.5538 Remote Similarity NPC328567
0.5538 Remote Similarity NPC486102
0.5517 Remote Similarity NPC46591
0.551 Remote Similarity NPC31530
0.549 Remote Similarity NPC115207
0.549 Remote Similarity NPC158079
0.549 Remote Similarity NPC228346
0.549 Remote Similarity NPC222127
0.549 Remote Similarity NPC40432
0.549 Remote Similarity NPC161557
0.549 Remote Similarity NPC82862
0.5424 Remote Similarity NPC477695
0.54 Remote Similarity NPC72046
0.54 Remote Similarity NPC261812
0.54 Remote Similarity NPC65183
0.5397 Remote Similarity NPC265154
0.5385 Remote Similarity NPC326095
0.5373 Remote Similarity NPC320671
0.5357 Remote Similarity NPC27843
0.5357 Remote Similarity NPC7171
0.5303 Remote Similarity NPC470826
0.5263 Remote Similarity NPC177868
0.5167 Remote Similarity NPC166884
0.5167 Remote Similarity NPC141569
0.5167 Remote Similarity NPC477701
0.5082 Remote Similarity NPC287124
0.5082 Remote Similarity NPC477700
0.507 Remote Similarity NPC486100
0.507 Remote Similarity NPC486101
0.5067 Remote Similarity NPC486099

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC185071 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