Natural Product: NPC24257

Natural Product IDNPC24257
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (7'r,8's)-3,4-Methylenedioxy-3',4'-Dimethoxy-7,8-Seco-7,7'-Epoxylignan-7,8-Dione
IUPAC Name [(1R,2S)-1-(3,4-dimethoxyphenyl)-2-methyl-3-oxobutyl] 1,3-benzodioxole-5-carboxylate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3290505
PubChem CID 90682208
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0001097] Benzyloxycarbonyls

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 JTXRNQSIUILDTQ-MPBGBICISA-N
Standard InCHI InChI=1S/C21H22O7/c1-12(13(2)22)20(14-5-7-16(24-3)18(9-14)25-4)28-21(23)15-6-8-17-19(10-15)27-11-26-17/h5-10,12,20H,11H2,1-4H3/t12-,20-/m1/s1
SMILES COc1cc(ccc1OC)[C@@H]([C@@H](C(=O)C)C)OC(=O)c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.14 Volume:   386.543
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Van der Waals volume.
Dense:   0.999 LogP:   2.934
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.064
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.478
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   18.0
TPSA:   80.29
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.673 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.057 Fsp3:   0.333
MCE-18:   58.357
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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:   0.16 Fluc inhibitor:   0.594
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.054
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.289
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.323 Promiscuous compounds:   0.191

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.95 MDCK Permeability:   -4.756
Pgp-inhibitor:   0.676 Pgp-substrate:   0.002
PAMPA:   0.208
?
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%):   0.014 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.364

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.016 MRP1:   0.928
Plasma Protein Binding (PPB):   98.012% Volume Distribution (VD):   -0.033
Fu: 1.858%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.356
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.113
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.04 CYP1A2-substrate:   0.967
CYP2C19-inhibitor:   0.919 CYP2C19-substrate:   0.753
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.133
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.984
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.967
HLM stability:   0.304
?
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):  5.16 Half-life (T1/2):  0.607

ADMET: Toxicity

hERG Blockers:  0.1 hERG Blockers (10um):  0.481
Human Hepatotoxicity (H-HT):  0.349 Drug-induced Liver Injury (DILI):  0.856
AMES Toxicity:  0.606 Rat Oral Acute Toxicity:  0.361
Maximum Recommended Daily Dose:  0.304 Skin Sensitization:  0.62
Carcinogencity:  0.755 Eye Corrosion:  0.055
Eye Irritation:  0.856 Respiratory Toxicity:  0.356
Drug-induced Neurotoxicity:  0.833 Ototoxicity:  0.165
Hematotoxicity:  0.347 Drug-induced Nephrotoxicity:  0.435
Genotoxicity:  0.858 RPMI-8226 Immunitoxicity:  0.14
A549 Cytotoxicity:  0.19 Hek293 Cytotoxicity:  0.326
BCF:   0.955
?
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:   3.886
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.933
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.63
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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
NPO19979 Schisandra glaucescens Species Schisandraceae Eukaryota n.a. stem n.a. PMID[23373215]
NPO19979 Schisandra glaucescens Species Schisandraceae Eukaryota fruit n.a. n.a. PMID[24927000]
NPO19979 Schisandra glaucescens Species Schisandraceae 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
NPT78 Individual protein Beta amyloid A4 protein Homo sapiens Activity = 53.2 % PMID[23398362]
NPT78 Individual protein Beta amyloid A4 protein Homo sapiens Activity = 62.0 % PMID[20695427]
NPT78 Individual protein Beta amyloid A4 protein Homo sapiens Activity = 63.5 % PMID[1965654]
NPT78 Individual protein Beta amyloid A4 protein Homo sapiens Activity = 63.4 % PubChem BioAssay data set

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 NPC24257 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 NPC153620
0.8478 Intermediate Similarity NPC254120
0.75 Intermediate Similarity NPC43514
0.6275 Remote Similarity NPC57119
0.6275 Remote Similarity NPC158471
0.6275 Remote Similarity NPC226862
0.6078 Remote Similarity NPC213482
0.5741 Remote Similarity NPC227160
0.5741 Remote Similarity NPC82111
0.5741 Remote Similarity NPC483654
0.549 Remote Similarity NPC271208
0.549 Remote Similarity NPC233224
0.549 Remote Similarity NPC610263
0.5357 Remote Similarity NPC136750
0.5357 Remote Similarity NPC266848
0.5333 Remote Similarity NPC488988
0.5254 Remote Similarity NPC488987
0.5185 Remote Similarity NPC480478

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC24257 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