Natural Product: NPC252307

Natural Product IDNPC252307
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Diosniponol B
IUPAC Name (2S,4S,6S)-2-(4-hydroxy-3-methoxyphenyl)-6-[2-(4-hydroxy-3-methoxyphenyl)ethyl]oxan-4-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2398581
PubChem CID 71680770
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids

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 JVJOETZYMWSWLO-BXWFABGCSA-N
Standard InCHI InChI=1S/C21H26O6/c1-25-20-9-13(4-7-17(20)23)3-6-16-11-15(22)12-19(27-16)14-5-8-18(24)21(10-14)26-2/h4-5,7-10,15-16,19,22-24H,3,6,11-12H2,1-2H3/t15-,16-,19-/m0/s1
SMILES COc1cc(CC[C@H]2C[C@H](O)C[C@H](O2)c2ccc(c(c2)OC)O)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.17 Volume:   383.025
?
Van der Waals volume.
Dense:   0.977 LogP:   1.699
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.999
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.161
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   88.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.719 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.337 Fsp3:   0.429
MCE-18:   60.0
?
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:   0.556 Fluc inhibitor:   0.342
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.029
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.241
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.184 Promiscuous compounds:   0.506

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.074 MDCK Permeability:   -4.822
Pgp-inhibitor:   0.098 Pgp-substrate:   0.84
PAMPA:   0.064
?
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%):   0.052 30% Bioavailability (F30%):   0.613
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.642
Plasma Protein Binding (PPB):   85.609% Volume Distribution (VD):   -0.159
Fu: 15.99%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.77
BSEP inhibitor:   0.875

ADMET: Metabolism

CYP1A2-inhibitor:   0.384 CYP1A2-substrate:   0.624
CYP2C19-inhibitor:   0.937 CYP2C19-substrate:   0.653
CYP2C9-inhibitor:   0.016 CYP2C9-substrate:   0.02
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.94
CYP3A4-inhibitor:   0.918 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.542
?
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):  8.695 Half-life (T1/2):  1.987

ADMET: Toxicity

hERG Blockers:  0.268 hERG Blockers (10um):  0.65
Human Hepatotoxicity (H-HT):  0.642 Drug-induced Liver Injury (DILI):  0.184
AMES Toxicity:  0.812 Rat Oral Acute Toxicity:  0.469
Maximum Recommended Daily Dose:  0.954 Skin Sensitization:  0.948
Carcinogencity:  0.458 Eye Corrosion:  0.016
Eye Irritation:  0.732 Respiratory Toxicity:  0.774
Drug-induced Neurotoxicity:  0.714 Ototoxicity:  0.454
Hematotoxicity:  0.239 Drug-induced Nephrotoxicity:  0.809
Genotoxicity:  0.264 RPMI-8226 Immunitoxicity:  0.173
A549 Cytotoxicity:  0.95 Hek293 Cytotoxicity:  0.761
BCF:   1.085
?
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:   3.697
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.946
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.323
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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
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota rhizomes n.a. n.a. PMID[23707257]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14409 Dioscorea nipponica Species Dioscoreaceae 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
NPT34 Cell line BV-2 Mus musculus Activity = 115.6 % PMID[22931300]
NPT34 Cell line BV-2 Mus musculus IC50 = 45920.0 nM PMID[22694318]

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 NPC252307 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 NPC245826
0.6949 Remote Similarity NPC474178
0.6949 Remote Similarity NPC1903
0.6935 Remote Similarity NPC201587
0.6935 Remote Similarity NPC253105
0.6727 Remote Similarity NPC153795
0.6727 Remote Similarity NPC42911
0.5517 Remote Similarity NPC481914
0.5429 Remote Similarity NPC52277
0.5397 Remote Similarity NPC20287
0.5397 Remote Similarity NPC20404
0.5357 Remote Similarity NPC312675
0.5357 Remote Similarity NPC262156
0.5357 Remote Similarity NPC184651
0.5357 Remote Similarity NPC113865
0.5333 Remote Similarity NPC164386
0.5312 Remote Similarity NPC12022
0.5312 Remote Similarity NPC278308
0.5273 Remote Similarity NPC299406
0.5246 Remote Similarity NPC137427
0.5167 Remote Similarity NPC53305
0.5161 Remote Similarity NPC311595
0.5161 Remote Similarity NPC481913
0.5161 Remote Similarity NPC24474
0.5135 Remote Similarity NPC199459
0.5094 Remote Similarity NPC8547
0.5088 Remote Similarity NPC127937
0.5082 Remote Similarity NPC303680

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC252307 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