Natural Product: NPC149008

Natural Product IDNPC149008
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Deoxyschisandrin
IUPAC Name n.a.
Synonyms Deoxyschisandrin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL490126
PubChem CID 9802006
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000238] Tannins
        • [CHEMONTID:0001710] Hydrolyzable tannins

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 JEJFTTRHGBKKEI-KBPBESRZSA-N
Standard InCHI InChI=1S/C24H32O6/c1-13-9-15-11-17(25-3)21(27-5)23(29-7)19(15)20-16(10-14(13)2)12-18(26-4)22(28-6)24(20)30-8/h11-14H,9-10H2,1-8H3/t13-,14-/m0/s1
SMILES COc1c2c(C[C@H](C)[C@H](Cc3c2c(OC)c(c(c3)OC)OC)C)cc(c1OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.22 Volume:   434.913
?
Van der Waals volume.
Dense:   0.957 LogP:   2.784
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.022
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.09
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   55.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.676 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.258 Fsp3:   0.5
MCE-18:   67.667
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.289 Fluc inhibitor:   0.334
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.361
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.207
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.34 Promiscuous compounds:   0.579

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.566 MDCK Permeability:   -4.574
Pgp-inhibitor:   0.315 Pgp-substrate:   0.178
PAMPA:   0.007
?
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%):   0.008 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.155

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.817 MRP1:   0.997
Plasma Protein Binding (PPB):   87.947% Volume Distribution (VD):   0.099
Fu: 8.98%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.955
OATP1B3 inhibitor:   0.973 BCRP inhibitor:   0.156
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.361 CYP1A2-substrate:   0.504
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.977
CYP2C9-inhibitor:   0.07 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.31 CYP2D6-substrate:   0.975
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.008 CYP2C8-inhibitor:   0.997
HLM stability:   0.896
?
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):  6.608 Half-life (T1/2):  0.815

ADMET: Toxicity

hERG Blockers:  0.272 hERG Blockers (10um):  0.623
Human Hepatotoxicity (H-HT):  0.528 Drug-induced Liver Injury (DILI):  0.452
AMES Toxicity:  0.402 Rat Oral Acute Toxicity:  0.4
Maximum Recommended Daily Dose:  0.5 Skin Sensitization:  0.471
Carcinogencity:  0.849 Eye Corrosion:  0.006
Eye Irritation:  0.527 Respiratory Toxicity:  0.84
Drug-induced Neurotoxicity:  0.688 Ototoxicity:  0.548
Hematotoxicity:  0.636 Drug-induced Nephrotoxicity:  0.38
Genotoxicity:  0.036 RPMI-8226 Immunitoxicity:  0.164
A549 Cytotoxicity:  0.435 Hek293 Cytotoxicity:  0.495
BCF:   3.046
?
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:   4.536
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.283
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.089
?
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
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. leaf n.a. PMID[16494492]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. stem n.a. PMID[16494492]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[16562834]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. fruit n.a. PMID[17190445]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota fruits n.a. n.a. PMID[17190445]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[17489633]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota leaves and stems n.a. n.a. PMID[20146529]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota fruits n.a. n.a. PMID[23265871]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. fruit n.a. PMID[24155209]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[24959987]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[25302569]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24804 Schisandra rubriflora 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT759 Cell line H9 Homo sapiens IC50 > 60000.0 nM PMID[17190445]

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 NPC149008 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 NPC283114
1.0 High Similarity NPC207702
0.7838 Intermediate Similarity NPC145722
0.7838 Intermediate Similarity NPC256776
0.7838 Intermediate Similarity NPC185680
0.7297 Intermediate Similarity NPC32189
0.6829 Remote Similarity NPC206737
0.6829 Remote Similarity NPC289258
0.6829 Remote Similarity NPC611061
0.6571 Remote Similarity NPC471182
0.6512 Remote Similarity NPC141493
0.65 Remote Similarity NPC102256
0.6364 Remote Similarity NPC865
0.6222 Remote Similarity NPC184928
0.5957 Remote Similarity NPC184684
0.5957 Remote Similarity NPC184641
0.5833 Remote Similarity NPC220577
0.5714 Remote Similarity NPC230538
0.5714 Remote Similarity NPC229172
0.5714 Remote Similarity NPC103637
0.5714 Remote Similarity NPC301765
0.5714 Remote Similarity NPC36531
0.5526 Remote Similarity NPC276026
0.551 Remote Similarity NPC137352
0.551 Remote Similarity NPC183083
0.551 Remote Similarity NPC485503
0.549 Remote Similarity NPC76415
0.549 Remote Similarity NPC218510
0.549 Remote Similarity NPC477381
0.5417 Remote Similarity NPC240279
0.5417 Remote Similarity NPC53722
0.5417 Remote Similarity NPC201404
0.5417 Remote Similarity NPC290714
0.5385 Remote Similarity NPC477879
0.5306 Remote Similarity NPC172171
0.5306 Remote Similarity NPC239254
0.5306 Remote Similarity NPC46277
0.5306 Remote Similarity NPC133934
0.525 Remote Similarity NPC471986
0.5185 Remote Similarity NPC471183
0.5111 Remote Similarity NPC555
0.5111 Remote Similarity NPC7515
0.5098 Remote Similarity NPC304821
0.5091 Remote Similarity NPC249070

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC149008 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