Natural Product: NPC57268

Natural Product IDNPC57268
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2,5-Bis-(3,4-Dimethoxy-Phenyl)-3,4-Dimethyl-Tetrahydro-Furan
IUPAC Name (2S,3S,4S,5S)-2,5-bis(3,4-dimethoxyphenyl)-3,4-dimethyloxolane
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL56917
PubChem CID 11975378
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003423] 7,7'-epoxylignans

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 JLJAVUZBHSLLJL-WJWAULOUSA-N
Standard InCHI InChI=1S/C22H28O5/c1-13-14(2)22(16-8-10-18(24-4)20(12-16)26-6)27-21(13)15-7-9-17(23-3)19(11-15)25-5/h7-14,21-22H,1-6H3/t13-,14-,21-,22-/m0/s1
SMILES COc1cc(ccc1OC)[C@H]1O[C@@H]([C@H]([C@@H]1C)C)c1ccc(c(c1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.19 Volume:   391.531
?
Van der Waals volume.
Dense:   0.951 LogP:   2.351
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.661
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.979
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   46.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.728 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.194 Fsp3:   0.455
MCE-18:   61.75
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.324 Fluc inhibitor:   0.419
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.024
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.037
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.336 Promiscuous compounds:   0.207

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.926 MDCK Permeability:   -4.717
Pgp-inhibitor:   0.933 Pgp-substrate:   0.14
PAMPA:   0.006
?
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):   0.008
20% Bioavailability (F20%):   0.02 30% Bioavailability (F30%):   0.02
50% Bioavailability (F50%):   0.412

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.058 MRP1:   0.886
Plasma Protein Binding (PPB):   90.468% Volume Distribution (VD):   0.232
Fu: 7.059%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.987
OATP1B3 inhibitor:   0.984 BCRP inhibitor:   0.813
BSEP inhibitor:   0.989

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.442
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.996
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.038
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.869
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.135
?
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):  9.034 Half-life (T1/2):  2.229

ADMET: Toxicity

hERG Blockers:  0.212 hERG Blockers (10um):  0.557
Human Hepatotoxicity (H-HT):  0.599 Drug-induced Liver Injury (DILI):  0.763
AMES Toxicity:  0.579 Rat Oral Acute Toxicity:  0.3
Maximum Recommended Daily Dose:  0.276 Skin Sensitization:  0.294
Carcinogencity:  0.76 Eye Corrosion:  0.211
Eye Irritation:  0.84 Respiratory Toxicity:  0.722
Drug-induced Neurotoxicity:  0.712 Ototoxicity:  0.339
Hematotoxicity:  0.532 Drug-induced Nephrotoxicity:  0.443
Genotoxicity:  0.226 RPMI-8226 Immunitoxicity:  0.119
A549 Cytotoxicity:  0.161 Hek293 Cytotoxicity:  0.391
BCF:   2.415
?
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:   3.952
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.481
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.789
?
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
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[11040054]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[16724856]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. leaf n.a. PMID[17999353]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota Roots; Tubers n.a. n.a. PMID[19639966]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[19900811]
NPO9925 Rhododendron latoucheae Species Ericaceae Eukaryota Twigs; Leaves n.a. n.a. PMID[30106288]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[8237383]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. aerial part n.a. PMID[8237383]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[8368081]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19174 Anoplophora chinensis Species Cerambycidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO313 Castilleja sulphurea Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9301 Dioscorea sativa Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1155 Forsythia japonica Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6475 Gymnosporia trigyna Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9480 Huperzia miyoshiana Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9571 Pseudobrickellia brasiliensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9925 Rhododendron latoucheae Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7522 Streptomyces amakusaensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9480 Huperzia miyoshiana Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9480 Huperzia miyoshiana Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6475 Gymnosporia trigyna Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1155 Forsythia japonica Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9480 Huperzia miyoshiana Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19174 Anoplophora chinensis Species Cerambycidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9925 Rhododendron latoucheae Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7522 Streptomyces amakusaensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO9301 Dioscorea sativa Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9571 Pseudobrickellia brasiliensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO313 Castilleja sulphurea Species Orobanchaceae 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
NPT1372 Individual protein Platelet activating factor receptor Cavia porcellus IC50 = 4500.0 nM PMID[3020247]

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 NPC57268 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 NPC216929
1.0 High Similarity NPC312713
1.0 High Similarity NPC126935
1.0 High Similarity NPC65933
1.0 High Similarity NPC172676
0.8824 High Similarity NPC50683
0.8824 High Similarity NPC112571
0.8824 High Similarity NPC285725
0.8108 Intermediate Similarity NPC57119
0.8108 Intermediate Similarity NPC158471
0.8108 Intermediate Similarity NPC226862
0.7692 Intermediate Similarity NPC158331
0.75 Intermediate Similarity NPC136750
0.75 Intermediate Similarity NPC487684
0.75 Intermediate Similarity NPC266848
0.7317 Intermediate Similarity NPC11258
0.7317 Intermediate Similarity NPC21867
0.7317 Intermediate Similarity NPC45774
0.7317 Intermediate Similarity NPC74914
0.7027 Intermediate Similarity NPC271208
0.7027 Intermediate Similarity NPC233224
0.7027 Intermediate Similarity NPC610263
0.6765 Remote Similarity NPC9891
0.6765 Remote Similarity NPC88297
0.6765 Remote Similarity NPC186845
0.6667 Remote Similarity NPC260842
0.6667 Remote Similarity NPC93783
0.6667 Remote Similarity NPC320380
0.6316 Remote Similarity NPC121783
0.6316 Remote Similarity NPC34902
0.6316 Remote Similarity NPC18449
0.5957 Remote Similarity NPC135777
0.5957 Remote Similarity NPC7744
0.5833 Remote Similarity NPC142547
0.5833 Remote Similarity NPC228469
0.5833 Remote Similarity NPC488984
0.5833 Remote Similarity NPC488985
0.5769 Remote Similarity NPC302506
0.5769 Remote Similarity NPC241846
0.5769 Remote Similarity NPC93610
0.575 Remote Similarity NPC31530
0.5714 Remote Similarity NPC222127
0.5714 Remote Similarity NPC82862
0.5682 Remote Similarity NPC254120
0.561 Remote Similarity NPC282703
0.561 Remote Similarity NPC184733
0.561 Remote Similarity NPC72046
0.561 Remote Similarity NPC261812
0.561 Remote Similarity NPC128208
0.561 Remote Similarity NPC129570
0.561 Remote Similarity NPC65183
0.561 Remote Similarity NPC63238
0.561 Remote Similarity NPC602603
0.5581 Remote Similarity NPC606146
0.5577 Remote Similarity NPC179521
0.5556 Remote Similarity NPC487685
0.5476 Remote Similarity NPC204215
0.5455 Remote Similarity NPC470372
0.5435 Remote Similarity NPC487683
0.5333 Remote Similarity NPC227160
0.5333 Remote Similarity NPC82111
0.5333 Remote Similarity NPC483654
0.5273 Remote Similarity NPC77861
0.5217 Remote Similarity NPC488505
0.5208 Remote Similarity NPC488986
0.5143 Remote Similarity NPC258425
0.5111 Remote Similarity NPC175067

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC57268 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