Natural Product: NPC27843

Natural Product IDNPC27843
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Phillygenin
IUPAC Name 4-[(3S,3aR,6R,6aR)-6-(3,4-dimethoxyphenyl)-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]furan-3-yl]-2-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2260010
PubChem CID 3083590
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 CPJKKWDCUOOTEW-YJPXFSGGSA-N
Standard InCHI InChI=1S/C21H24O6/c1-23-17-7-5-13(9-19(17)25-3)21-15-11-26-20(14(15)10-27-21)12-4-6-16(22)18(8-12)24-2/h4-9,14-15,20-22H,10-11H2,1-3H3/t14-,15-,20+,21-/m0/s1
SMILES COc1ccc(cc1OC)[C@H]1[C@H]2CO[C@H](c3ccc(c(c3)OC)O)[C@H]2CO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.16 Volume:   374.469
?
Van der Waals volume.
Dense:   0.994 LogP:   1.487
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.894
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.671
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   21.0
TPSA:   66.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.867 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.578 Fsp3:   0.429
MCE-18:   74.8
?
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:   0.383 Fluc inhibitor:   0.431
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.032
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.058
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.274 Promiscuous compounds:   0.299

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.193 MDCK Permeability:   -4.852
Pgp-inhibitor:   0.194 Pgp-substrate:   0.051
PAMPA:   0.007
?
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):   0.001
20% Bioavailability (F20%):   0.112 30% Bioavailability (F30%):   0.307
50% Bioavailability (F50%):   0.944

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.701
Plasma Protein Binding (PPB):   87.934% Volume Distribution (VD):   -0.026
Fu: 12.858%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.204
BSEP inhibitor:   0.734

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.31
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.418
CYP2C9-inhibitor:   0.092 CYP2C9-substrate:   0.078
CYP2D6-inhibitor:   0.996 CYP2D6-substrate:   0.661
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.202
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.784
HLM stability:   0.259
?
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):  8.64 Half-life (T1/2):  2.214

ADMET: Toxicity

hERG Blockers:  0.099 hERG Blockers (10um):  0.495
Human Hepatotoxicity (H-HT):  0.671 Drug-induced Liver Injury (DILI):  0.76
AMES Toxicity:  0.745 Rat Oral Acute Toxicity:  0.23
Maximum Recommended Daily Dose:  0.322 Skin Sensitization:  0.817
Carcinogencity:  0.459 Eye Corrosion:  0.101
Eye Irritation:  0.988 Respiratory Toxicity:  0.525
Drug-induced Neurotoxicity:  0.368 Ototoxicity:  0.231
Hematotoxicity:  0.388 Drug-induced Nephrotoxicity:  0.567
Genotoxicity:  0.713 RPMI-8226 Immunitoxicity:  0.117
A549 Cytotoxicity:  0.127 Hek293 Cytotoxicity:  0.271
BCF:   1.213
?
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:   3.736
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.064
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.449
?
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
NPO19805 Forsythia viridissima Species Oleaceae Eukaryota n.a. flower n.a. PMID[15481244]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. PMID[17156960]
NPO16665 Tephrosia semiglabra Species Geometridae Eukaryota n.a. n.a. n.a. PMID[2089123]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. PMID[26422318]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota Fruits n.a. n.a. PMID[28218000]
NPO19805 Forsythia viridissima Species Oleaceae Eukaryota Roots n.a. n.a. PMID[30676026]
NPO13234 Gyalolechia fulgida Species Teloschistaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11024 Bellardia viscosa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17547 Dryopteris arguta Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO984 Hippocrepis emerus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17401 Kopsia lapidilecta Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22661 Pinus aristata Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18852 Plenckia populnea Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16665 Tephrosia semiglabra Species Geometridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19805 Forsythia viridissima Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22661 Pinus aristata Species Pinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19805 Forsythia viridissima Species Oleaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19805 Forsythia viridissima Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22661 Pinus aristata Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19805 Forsythia viridissima Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28588 Lindera praecox Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16665 Tephrosia semiglabra Species Geometridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17547 Dryopteris arguta Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13234 Gyalolechia fulgida Species Teloschistaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11024 Bellardia viscosa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO984 Hippocrepis emerus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22661 Pinus aristata Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18852 Plenckia populnea Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17401 Kopsia lapidilecta Species Apocynaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 2440.39 umol/g DOI[10.1007/s00044-009-9217-5]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 3.58 ug.mL-1 DOI[10.1007/s00044-009-9217-5]
NPT1 Others Radical scavenging activity n.a. IC50 = 15.51 ug.mL-1 DOI[10.1007/s00044-009-9217-5]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity = 7.932 nmol/ml DOI[10.1007/s00044-009-9217-5]
NPT32 Organism Mus musculus Mus musculus Activity = 2.457 mmol/L DOI[10.1007/s00044-009-9217-5]
NPT32 Organism Mus musculus Mus musculus Activity = 3.186 mmol/L DOI[10.1007/s00044-009-9217-5]
NPT32 Organism Mus musculus Mus musculus Activity = 0.3249 mmol/L DOI[10.1007/s00044-009-9217-5]
NPT32 Organism Mus musculus Mus musculus Activity = 7.212 mmol/L DOI[10.1007/s00044-009-9217-5]





 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 NPC27843 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 NPC7171
0.8372 Intermediate Similarity NPC115207
0.8372 Intermediate Similarity NPC158079
0.8372 Intermediate Similarity NPC228346
0.8372 Intermediate Similarity NPC40432
0.8372 Intermediate Similarity NPC161557
0.82 Intermediate Similarity NPC88640
0.82 Intermediate Similarity NPC101153
0.82 Intermediate Similarity NPC193666
0.82 Intermediate Similarity NPC123526
0.82 Intermediate Similarity NPC608725
0.766 Intermediate Similarity NPC126409
0.766 Intermediate Similarity NPC99572
0.7442 Intermediate Similarity NPC121783
0.7442 Intermediate Similarity NPC34902
0.7442 Intermediate Similarity NPC18449
0.7143 Intermediate Similarity NPC11258
0.7143 Intermediate Similarity NPC21867
0.7143 Intermediate Similarity NPC45774
0.7143 Intermediate Similarity NPC74914
0.6809 Remote Similarity NPC222127
0.6809 Remote Similarity NPC82862
0.6724 Remote Similarity NPC265154
0.6667 Remote Similarity NPC38041
0.6667 Remote Similarity NPC22150
0.6604 Remote Similarity NPC223185
0.6604 Remote Similarity NPC610778
0.6538 Remote Similarity NPC478955
0.6538 Remote Similarity NPC478700
0.6508 Remote Similarity NPC114119
0.6508 Remote Similarity NPC471415
0.6481 Remote Similarity NPC298317
0.6481 Remote Similarity NPC255566
0.64 Remote Similarity NPC227160
0.64 Remote Similarity NPC82111
0.6327 Remote Similarity NPC606146
0.6271 Remote Similarity NPC64201
0.6129 Remote Similarity NPC470097
0.6078 Remote Similarity NPC469480
0.6 Remote Similarity NPC165155
0.6 Remote Similarity NPC24490
0.5957 Remote Similarity NPC141765
0.5957 Remote Similarity NPC34103
0.5932 Remote Similarity NPC67247
0.5893 Remote Similarity NPC142547
0.5893 Remote Similarity NPC228469
0.5806 Remote Similarity NPC487682
0.58 Remote Similarity NPC142985
0.5769 Remote Similarity NPC147379
0.5758 Remote Similarity NPC51328
0.5758 Remote Similarity NPC55158
0.5733 Remote Similarity NPC11411
0.5714 Remote Similarity NPC282703
0.5714 Remote Similarity NPC184733
0.5714 Remote Similarity NPC128208
0.5714 Remote Similarity NPC129570
0.5714 Remote Similarity NPC63238
0.5714 Remote Similarity NPC602603
0.5672 Remote Similarity NPC324492
0.5672 Remote Similarity NPC317053
0.566 Remote Similarity NPC488505
0.5645 Remote Similarity NPC470098
0.5645 Remote Similarity NPC473266
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
0.5584 Remote Similarity NPC105137
0.5556 Remote Similarity NPC189474
0.5556 Remote Similarity NPC487683
0.5522 Remote Similarity NPC286235
0.5517 Remote Similarity NPC474139
0.5517 Remote Similarity NPC471942
0.5513 Remote Similarity NPC7191
0.5513 Remote Similarity NPC149873
0.55 Remote Similarity NPC488545
0.55 Remote Similarity NPC488546
0.549 Remote Similarity NPC242807
0.549 Remote Similarity NPC153739
0.5479 Remote Similarity NPC478055
0.5472 Remote Similarity NPC158331
0.5469 Remote Similarity NPC281780
0.5469 Remote Similarity NPC267091
0.5441 Remote Similarity NPC279298
0.5424 Remote Similarity NPC272
0.5424 Remote Similarity NPC187998
0.5424 Remote Similarity NPC77040
0.5424 Remote Similarity NPC257582
0.5424 Remote Similarity NPC241522
0.5424 Remote Similarity NPC485398
0.541 Remote Similarity NPC55793
0.5397 Remote Similarity NPC246947
0.5397 Remote Similarity NPC77861
0.537 Remote Similarity NPC487684
0.5357 Remote Similarity NPC185071
0.5357 Remote Similarity NPC488986
0.5345 Remote Similarity NPC181049
0.5319 Remote Similarity NPC281864
0.5319 Remote Similarity NPC328682
0.5319 Remote Similarity NPC54321
0.5303 Remote Similarity NPC470826
0.5294 Remote Similarity NPC67467
0.5273 Remote Similarity NPC479434
0.5246 Remote Similarity NPC282833
0.5246 Remote Similarity NPC145144
0.5238 Remote Similarity NPC276753
0.5238 Remote Similarity NPC205796
0.5208 Remote Similarity NPC146355
0.5208 Remote Similarity NPC131747
0.5208 Remote Similarity NPC257682
0.5172 Remote Similarity NPC30890
0.5094 Remote Similarity NPC4940
0.5079 Remote Similarity NPC43514
0.5072 Remote Similarity NPC252402
0.5072 Remote Similarity NPC102934

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC27843 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