Natural Product: NPC317769

Natural Product IDNPC317769
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3,4-Divanillyltetrahydrofuran
IUPAC Name 4-[[4-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-3-yl]methyl]-2-methoxyphenol
Synonyms 3,4-Divanillyltetrahydrofuran
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL405043
PubChem CID 182210
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003424] 9,9'-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 ROGUIJKVZZROIQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H24O5/c1-23-19-9-13(3-5-17(19)21)7-15-11-25-12-16(15)8-14-4-6-18(22)20(10-14)24-2/h3-6,9-10,15-16,21-22H,7-8,11-12H2,1-2H3
SMILES COC1=C(C=CC(=C1)CC2COCC2CC3=CC(=C(C=C3)O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.16 Volume:   356.939
?
Van der Waals volume.
Dense:   0.964 LogP:   2.005
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.2
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.005
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   68.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.842 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.155 Fsp3:   0.4
MCE-18:   55.857
?
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:   0.214 Fluc inhibitor:   0.009
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.009
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.499
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.226 Promiscuous compounds:   0.448

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.56 MDCK Permeability:   -5.095
Pgp-inhibitor:   0.28 Pgp-substrate:   0.137
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):   0.0
20% Bioavailability (F20%):   0.181 30% Bioavailability (F30%):   0.17
50% Bioavailability (F50%):   0.908

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.042 MRP1:   0.993
Plasma Protein Binding (PPB):   87.415% Volume Distribution (VD):   -0.135
Fu: 14.09%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.072
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.895 CYP1A2-substrate:   0.67
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.981
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.943
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.997 CYP3A4-substrate:   0.14
CYP2B6-substrate:   0.037 CYP2C8-inhibitor:   1.0
HLM stability:   0.971
?
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):  8.276 Half-life (T1/2):  1.199

ADMET: Toxicity

hERG Blockers:  0.496 hERG Blockers (10um):  0.738
Human Hepatotoxicity (H-HT):  0.835 Drug-induced Liver Injury (DILI):  0.295
AMES Toxicity:  0.573 Rat Oral Acute Toxicity:  0.146
Maximum Recommended Daily Dose:  0.7 Skin Sensitization:  0.99
Carcinogencity:  0.615 Eye Corrosion:  0.007
Eye Irritation:  0.708 Respiratory Toxicity:  0.764
Drug-induced Neurotoxicity:  0.592 Ototoxicity:  0.881
Hematotoxicity:  0.258 Drug-induced Nephrotoxicity:  0.797
Genotoxicity:  0.024 RPMI-8226 Immunitoxicity:  0.114
A549 Cytotoxicity:  0.282 Hek293 Cytotoxicity:  0.761
BCF:   1.701
?
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:   4.279
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.306
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.799
?
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
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. seed n.a. DOI[10.1016/S0031-9422(00)97029-8]
NPO13353 Sedum sarmentosum Species Crassulaceae Eukaryota n.a. aerial part n.a. PMID[15577228]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. fruit n.a. PMID[16417304]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. branch n.a. PMID[17202693]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota seeds n.a. n.a. PMID[18603435]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota Seeds n.a. n.a. PMID[20469887]
NPO13353 Sedum sarmentosum Species Crassulaceae Eukaryota n.a. n.a. n.a. PMID[22085682]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. n.a. n.a. PMID[37570937]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. n.a. n.a. PMID[38358042]
NPO13353 Sedum sarmentosum Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. n.a. Database[FooDB]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO13353 Sedum sarmentosum Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13353 Sedum sarmentosum Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13353 Sedum sarmentosum Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13353 Sedum sarmentosum Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15095 Hippophae rhamnoides Species Elaeagnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13353 Sedum sarmentosum Species Crassulaceae 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
NPT895 Individual protein Testis-specific androgen-binding protein Homo sapiens Kd = 309.03 nM PMID[18330978]

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 NPC317769 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 NPC31344
0.7447 Intermediate Similarity NPC475875
0.6809 Remote Similarity NPC68779
0.6809 Remote Similarity NPC108598
0.6809 Remote Similarity NPC173308
0.6809 Remote Similarity NPC181079
0.6809 Remote Similarity NPC487680
0.675 Remote Similarity NPC165133
0.675 Remote Similarity NPC242885
0.675 Remote Similarity NPC95614
0.675 Remote Similarity NPC232316
0.6531 Remote Similarity NPC275950
0.6471 Remote Similarity NPC187998
0.6471 Remote Similarity NPC257582
0.6471 Remote Similarity NPC241522
0.6429 Remote Similarity NPC85488
0.6346 Remote Similarity NPC110699
0.6346 Remote Similarity NPC106055
0.6275 Remote Similarity NPC273657
0.6226 Remote Similarity NPC486558
0.6226 Remote Similarity NPC606339
0.6154 Remote Similarity NPC156840
0.6111 Remote Similarity NPC485282
0.6111 Remote Similarity NPC67247
0.6111 Remote Similarity NPC485283
0.6111 Remote Similarity NPC485281
0.6111 Remote Similarity NPC610284
0.6078 Remote Similarity NPC253481
0.6078 Remote Similarity NPC253722
0.6038 Remote Similarity NPC106920
0.6038 Remote Similarity NPC300776
0.6038 Remote Similarity NPC15811
0.6038 Remote Similarity NPC176814
0.6038 Remote Similarity NPC4982
0.6038 Remote Similarity NPC606629
0.6 Remote Similarity NPC42300
0.5926 Remote Similarity NPC476345
0.5893 Remote Similarity NPC278961
0.5893 Remote Similarity NPC64201
0.5893 Remote Similarity NPC113680
0.587 Remote Similarity NPC56214
0.587 Remote Similarity NPC487676
0.5854 Remote Similarity NPC257124
0.5745 Remote Similarity NPC227217
0.5745 Remote Similarity NPC117780
0.5741 Remote Similarity NPC23646
0.5741 Remote Similarity NPC485397
0.5714 Remote Similarity NPC8547
0.5714 Remote Similarity NPC221049
0.5714 Remote Similarity NPC140359
0.5682 Remote Similarity NPC603326
0.5636 Remote Similarity NPC282833
0.5636 Remote Similarity NPC145144
0.5625 Remote Similarity NPC127587
0.5614 Remote Similarity NPC487679
0.5614 Remote Similarity NPC487678
0.5593 Remote Similarity NPC281780
0.5593 Remote Similarity NPC267091
0.5581 Remote Similarity NPC471693
0.5581 Remote Similarity NPC193544
0.5556 Remote Similarity NPC102908
0.5517 Remote Similarity NPC282291
0.5517 Remote Similarity NPC166137
0.5517 Remote Similarity NPC169973
0.5517 Remote Similarity NPC608199
0.551 Remote Similarity NPC5428
0.551 Remote Similarity NPC607444
0.5455 Remote Similarity NPC255675
0.5439 Remote Similarity NPC31751
0.5424 Remote Similarity NPC120852
0.5424 Remote Similarity NPC216223
0.54 Remote Similarity NPC603109
0.5357 Remote Similarity NPC100675
0.5357 Remote Similarity NPC101624
0.5357 Remote Similarity NPC184938
0.5357 Remote Similarity NPC90431
0.5357 Remote Similarity NPC601691
0.5333 Remote Similarity NPC57490
0.5333 Remote Similarity NPC603989
0.5319 Remote Similarity NPC115207
0.5319 Remote Similarity NPC158079
0.5319 Remote Similarity NPC177291
0.5319 Remote Similarity NPC228346
0.5319 Remote Similarity NPC40432
0.5319 Remote Similarity NPC161557
0.5217 Remote Similarity NPC197757
0.5217 Remote Similarity NPC17943
0.5217 Remote Similarity NPC299406
0.5192 Remote Similarity NPC274356
0.5192 Remote Similarity NPC101748
0.5179 Remote Similarity NPC610652
0.5161 Remote Similarity NPC478703
0.5161 Remote Similarity NPC478704
0.5161 Remote Similarity NPC604694
0.5156 Remote Similarity NPC67467
0.5102 Remote Similarity NPC51840
0.5091 Remote Similarity NPC471942

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC317769 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
0.5854 Remote Similarity NPD228 Phase 0

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