Natural Product: NPC158331

Natural Product IDNPC158331
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-(7S,8S,7'r,8'r)-4'-Dihydroxy-3,4,3',5'-Tetramethoxy-7,7'-Epoxylignan
IUPAC Name 4-[(2R,3R,4S,5S)-5-(3,4-dimethoxyphenyl)-3,4-dimethyloxolan-2-yl]-2,6-dimethoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3105538
PubChem CID 76317427
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 AGYZMBXYRZJNNA-AHIIRKPMSA-N
Standard InCHI InChI=1S/C22H28O6/c1-12-13(2)22(15-10-18(26-5)20(23)19(11-15)27-6)28-21(12)14-7-8-16(24-3)17(9-14)25-4/h7-13,21-23H,1-6H3/t12-,13+,21-,22+/m0/s1
SMILES COc1cc(ccc1OC)[C@H]1O[C@H]([C@@H]([C@@H]1C)C)c1cc(OC)c(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   388.19 Volume:   400.321
?
Van der Waals volume.
Dense:   0.97 LogP:   2.08
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.448
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.396
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   66.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.785 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.396 Fsp3:   0.455
MCE-18:   65.0
?
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:   0.146 Fluc inhibitor:   0.443
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.025
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.026
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.317 Promiscuous compounds:   0.172

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.278 MDCK Permeability:   -4.847
Pgp-inhibitor:   0.809 Pgp-substrate:   0.078
PAMPA:   0.001
?
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%):   0.009 30% Bioavailability (F30%):   0.006
50% Bioavailability (F50%):   0.792

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.041 MRP1:   0.983
Plasma Protein Binding (PPB):   94.869% Volume Distribution (VD):   -0.139
Fu: 4.303%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.623
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.142
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.99
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.722
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.016
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.015
?
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):  8.368 Half-life (T1/2):  2.124

ADMET: Toxicity

hERG Blockers:  0.198 hERG Blockers (10um):  0.58
Human Hepatotoxicity (H-HT):  0.495 Drug-induced Liver Injury (DILI):  0.634
AMES Toxicity:  0.519 Rat Oral Acute Toxicity:  0.369
Maximum Recommended Daily Dose:  0.419 Skin Sensitization:  0.319
Carcinogencity:  0.643 Eye Corrosion:  0.081
Eye Irritation:  0.835 Respiratory Toxicity:  0.727
Drug-induced Neurotoxicity:  0.617 Ototoxicity:  0.377
Hematotoxicity:  0.562 Drug-induced Nephrotoxicity:  0.292
Genotoxicity:  0.126 RPMI-8226 Immunitoxicity:  0.143
A549 Cytotoxicity:  0.223 Hek293 Cytotoxicity:  0.506
BCF:   1.53
?
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:   3.821
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.363
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.649
?
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
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[10924192]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[11754613]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. root n.a. PMID[14750033]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[15482936]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota roots n.a. n.a. PMID[18841903]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota Roots n.a. n.a. PMID[24359277]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota Aerial Parts n.a. n.a. PMID[24387347]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[31642320]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20323 Saururus chinensis Species Saururaceae 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
NPT164 Organism Human herpesvirus 4 Human herpesvirus 4 EC50 = 11600.0 nM PMID[11170658]
NPT2 Others Unspecified n.a. Ratio CC50/EC50 = 8.6 n.a. PMID[16643031]

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 NPC158331 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
0.7778 Intermediate Similarity NPC11258
0.7778 Intermediate Similarity NPC21867
0.7778 Intermediate Similarity NPC45774
0.7778 Intermediate Similarity NPC74914
0.7692 Intermediate Similarity NPC216929
0.7692 Intermediate Similarity NPC312713
0.7692 Intermediate Similarity NPC126935
0.7692 Intermediate Similarity NPC65933
0.7692 Intermediate Similarity NPC57268
0.7692 Intermediate Similarity NPC172676
0.7619 Intermediate Similarity NPC204215
0.7556 Intermediate Similarity NPC487684
0.7381 Intermediate Similarity NPC50683
0.7381 Intermediate Similarity NPC112571
0.7381 Intermediate Similarity NPC285725
0.6522 Remote Similarity NPC57119
0.6522 Remote Similarity NPC158471
0.6522 Remote Similarity NPC226862
0.6458 Remote Similarity NPC136750
0.6458 Remote Similarity NPC266848
0.6346 Remote Similarity NPC142547
0.6346 Remote Similarity NPC228469
0.6222 Remote Similarity NPC282703
0.6222 Remote Similarity NPC184733
0.6222 Remote Similarity NPC128208
0.6222 Remote Similarity NPC129570
0.6222 Remote Similarity NPC63238
0.6222 Remote Similarity NPC602603
0.6154 Remote Similarity NPC135777
0.6 Remote Similarity NPC487683
0.5849 Remote Similarity NPC260842
0.5849 Remote Similarity NPC93783
0.5849 Remote Similarity NPC320380
0.5833 Remote Similarity NPC326095
0.5778 Remote Similarity NPC244983
0.5769 Remote Similarity NPC488986
0.5763 Remote Similarity NPC77861
0.5741 Remote Similarity NPC298317
0.5741 Remote Similarity NPC255566
0.5741 Remote Similarity NPC488984
0.5741 Remote Similarity NPC488985
0.5714 Remote Similarity NPC9891
0.5714 Remote Similarity NPC88297
0.5714 Remote Similarity NPC186845
0.5667 Remote Similarity NPC470372
0.5652 Remote Similarity NPC271208
0.5652 Remote Similarity NPC233224
0.5652 Remote Similarity NPC610263
0.5472 Remote Similarity NPC27843
0.5472 Remote Similarity NPC7171
0.54 Remote Similarity NPC175067
0.52 Remote Similarity NPC165155
0.52 Remote Similarity NPC24490
0.5172 Remote Similarity NPC477702
0.5167 Remote Similarity NPC302506
0.5167 Remote Similarity NPC241846
0.5167 Remote Similarity NPC93610
0.5161 Remote Similarity NPC487682
0.5106 Remote Similarity NPC141765
0.5106 Remote Similarity NPC121783
0.5106 Remote Similarity NPC34902
0.5106 Remote Similarity NPC18449
0.5106 Remote Similarity NPC34103

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC158331 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