Natural Product: NPC266848

Natural Product IDNPC266848
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Rel-Saurufurin A
IUPAC Name 6-[(2S,3S,4S,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyloxolan-2-yl]-4-methoxy-1,3-benzodioxole
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3104949
PubChem CID 76310171
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 YCVPIUIGBBJALE-IRTBSJMASA-N
Standard InCHI InChI=1S/C22H26O6/c1-12-13(2)21(15-9-18(25-5)22-19(10-15)26-11-27-22)28-20(12)14-6-7-16(23-3)17(8-14)24-4/h6-10,12-13,20-21H,11H2,1-5H3/t12-,13-,20+,21-/m0/s1
SMILES COc1cc(ccc1OC)[C@@H]1O[C@@H]([C@H]([C@@H]1C)C)c1cc(OC)c2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.17 Volume:   391.765
?
Van der Waals volume.
Dense:   0.986 LogP:   2.57
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.867
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.545
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   21.0
TPSA:   55.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.753 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.527 Fsp3:   0.455
MCE-18:   76.188
?
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:   0.312 Fluc inhibitor:   0.738
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.037
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.045
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.271 Promiscuous compounds:   0.136

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.999 MDCK Permeability:   -4.742
Pgp-inhibitor:   0.849 Pgp-substrate:   0.028
PAMPA:   0.015
?
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%):   0.037 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.287

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.636 MRP1:   0.941
Plasma Protein Binding (PPB):   90.662% Volume Distribution (VD):   0.26
Fu: 6.778%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.971
OATP1B3 inhibitor:   0.957 BCRP inhibitor:   0.306
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.603
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.918
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.973
HLM stability:   0.016
?
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):  7.13 Half-life (T1/2):  1.462

ADMET: Toxicity

hERG Blockers:  0.243 hERG Blockers (10um):  0.459
Human Hepatotoxicity (H-HT):  0.811 Drug-induced Liver Injury (DILI):  0.939
AMES Toxicity:  0.604 Rat Oral Acute Toxicity:  0.442
Maximum Recommended Daily Dose:  0.421 Skin Sensitization:  0.453
Carcinogencity:  0.83 Eye Corrosion:  0.04
Eye Irritation:  0.732 Respiratory Toxicity:  0.821
Drug-induced Neurotoxicity:  0.681 Ototoxicity:  0.415
Hematotoxicity:  0.741 Drug-induced Nephrotoxicity:  0.593
Genotoxicity:  0.748 RPMI-8226 Immunitoxicity:  0.242
A549 Cytotoxicity:  0.501 Hek293 Cytotoxicity:  0.525
BCF:   2.314
?
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:   3.941
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.508
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.757
?
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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 54.4 % PMID[24387347]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 42.0 % PMID[24387347]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 19.1 % PMID[24387347]

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 NPC266848 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 NPC136750
0.8333 Intermediate Similarity NPC57119
0.8333 Intermediate Similarity NPC158471
0.8333 Intermediate Similarity NPC226862
0.825 Intermediate Similarity NPC31530
0.8049 Intermediate Similarity NPC50683
0.8049 Intermediate Similarity NPC72046
0.8049 Intermediate Similarity NPC261812
0.8049 Intermediate Similarity NPC112571
0.8049 Intermediate Similarity NPC65183
0.8049 Intermediate Similarity NPC285725
0.75 Intermediate Similarity NPC216929
0.75 Intermediate Similarity NPC312713
0.75 Intermediate Similarity NPC126935
0.75 Intermediate Similarity NPC65933
0.75 Intermediate Similarity NPC57268
0.75 Intermediate Similarity NPC172676
0.7381 Intermediate Similarity NPC271208
0.7381 Intermediate Similarity NPC233224
0.7381 Intermediate Similarity NPC610263
0.6471 Remote Similarity NPC177868
0.6458 Remote Similarity NPC158331
0.6346 Remote Similarity NPC135777
0.6346 Remote Similarity NPC7744
0.6341 Remote Similarity NPC9891
0.6341 Remote Similarity NPC88297
0.6341 Remote Similarity NPC186845
0.6226 Remote Similarity NPC142547
0.6226 Remote Similarity NPC228469
0.6226 Remote Similarity NPC488984
0.6226 Remote Similarity NPC488985
0.614 Remote Similarity NPC302506
0.614 Remote Similarity NPC241846
0.614 Remote Similarity NPC93610
0.6 Remote Similarity NPC487685
0.6 Remote Similarity NPC487684
0.5965 Remote Similarity NPC179521
0.5882 Remote Similarity NPC189474
0.5882 Remote Similarity NPC11258
0.5882 Remote Similarity NPC21867
0.5882 Remote Similarity NPC45774
0.5882 Remote Similarity NPC74914
0.5862 Remote Similarity NPC483651
0.58 Remote Similarity NPC227160
0.58 Remote Similarity NPC82111
0.58 Remote Similarity NPC483654
0.56 Remote Similarity NPC216434
0.56 Remote Similarity NPC103448
0.56 Remote Similarity NPC606558
0.551 Remote Similarity NPC148893
0.551 Remote Similarity NPC474295
0.551 Remote Similarity NPC480478
0.551 Remote Similarity NPC222127
0.551 Remote Similarity NPC25333
0.551 Remote Similarity NPC49235
0.551 Remote Similarity NPC82862
0.5455 Remote Similarity NPC260842
0.5455 Remote Similarity NPC93783
0.5455 Remote Similarity NPC320380
0.5439 Remote Similarity NPC166884
0.5439 Remote Similarity NPC141569
0.5439 Remote Similarity NPC477701
0.5357 Remote Similarity NPC24257
0.5357 Remote Similarity NPC153620
0.5345 Remote Similarity NPC287124
0.5345 Remote Similarity NPC477702
0.5306 Remote Similarity NPC204215
0.5152 Remote Similarity NPC226153
0.5079 Remote Similarity NPC487682
0.5075 Remote Similarity NPC304048

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC266848 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