Natural Product: NPC46277

Natural Product IDNPC46277
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Gomisin S
IUPAC Name n.a.
Synonyms Gomisin S
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2313596
PubChem CID 14213995
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 FNANNZAGLCKFOL-ZKTNFTSUSA-N
Standard InCHI InChI=1S/C23H30O7/c1-11-8-13-9-15(24)20(27-4)22(29-6)17(13)18-14(19(25)12(11)2)10-16(26-3)21(28-5)23(18)30-7/h9-12,19,24-25H,8H2,1-7H3/t11-,12-,19-/m0/s1
SMILES COc1cc2[C@@H](O)[C@@H](C)[C@@H](C)Cc3c(c2c(c1OC)OC)c(OC)c(c(c3)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   418.2 Volume:   426.408
?
Van der Waals volume.
Dense:   0.981 LogP:   2.921
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.9
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.868
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   86.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.76 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.703 Fsp3:   0.478
MCE-18:   71.176
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.297 Fluc inhibitor:   0.183
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.199
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.431
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.223 Promiscuous compounds:   0.529

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.069 MDCK Permeability:   -4.777
Pgp-inhibitor:   0.455 Pgp-substrate:   0.197
PAMPA:   0.088
?
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):   0.003
20% Bioavailability (F20%):   0.181 30% Bioavailability (F30%):   0.074
50% Bioavailability (F50%):   0.918

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.716 MRP1:   0.995
Plasma Protein Binding (PPB):   93.734% Volume Distribution (VD):   -0.154
Fu: 5.83%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.959
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.415
BSEP inhibitor:   0.764

ADMET: Metabolism

CYP1A2-inhibitor:   0.309 CYP1A2-substrate:   0.019
CYP2C19-inhibitor:   0.69 CYP2C19-substrate:   0.066
CYP2C9-inhibitor:   0.092 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.09
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.557
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.99
HLM stability:   0.383
?
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):  6.111 Half-life (T1/2):  1.667

ADMET: Toxicity

hERG Blockers:  0.158 hERG Blockers (10um):  0.628
Human Hepatotoxicity (H-HT):  0.535 Drug-induced Liver Injury (DILI):  0.534
AMES Toxicity:  0.671 Rat Oral Acute Toxicity:  0.621
Maximum Recommended Daily Dose:  0.546 Skin Sensitization:  0.894
Carcinogencity:  0.778 Eye Corrosion:  0.003
Eye Irritation:  0.397 Respiratory Toxicity:  0.879
Drug-induced Neurotoxicity:  0.788 Ototoxicity:  0.457
Hematotoxicity:  0.713 Drug-induced Nephrotoxicity:  0.668
Genotoxicity:  0.411 RPMI-8226 Immunitoxicity:  0.284
A549 Cytotoxicity:  0.836 Hek293 Cytotoxicity:  0.643
BCF:   1.638
?
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:   3.474
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.887
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.827
?
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
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[16562834]
NPO8584 Schisandra arisanensis Species Schisandraceae Eukaryota fruits n.a. n.a. PMID[19673515]
NPO8584 Schisandra arisanensis Species Schisandraceae Eukaryota fruits n.a. n.a. PMID[20536188]
NPO8584 Schisandra arisanensis Species Schisandraceae Eukaryota fruits n.a. n.a. PMID[23265871]
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]
NPO8584 Schisandra arisanensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8187 Schisandra chinensis 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]
NPO8187 Schisandra chinensis 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]
NPO8584 Schisandra arisanensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8584 Schisandra arisanensis 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]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8584 Schisandra arisanensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
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]

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
NPT2 Others Unspecified n.a. Inhibition = 49.2 % PMID[23265871]

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 NPC46277 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
0.7917 Intermediate Similarity NPC156948
0.7069 Intermediate Similarity NPC166506
0.7069 Intermediate Similarity NPC110763
0.7 Intermediate Similarity NPC149735
0.6786 Remote Similarity NPC230538
0.6786 Remote Similarity NPC229172
0.6786 Remote Similarity NPC103637
0.6786 Remote Similarity NPC301765
0.6786 Remote Similarity NPC36531
0.6552 Remote Similarity NPC477381
0.6491 Remote Similarity NPC3072
0.6441 Remote Similarity NPC477879
0.6429 Remote Similarity NPC172171
0.6429 Remote Similarity NPC239254
0.625 Remote Similarity NPC240279
0.617 Remote Similarity NPC276026
0.6129 Remote Similarity NPC249070
0.6 Remote Similarity NPC86605
0.5873 Remote Similarity NPC189239
0.5758 Remote Similarity NPC473323
0.5672 Remote Similarity NPC473425
0.5455 Remote Similarity NPC555
0.5455 Remote Similarity NPC324962
0.5455 Remote Similarity NPC7515
0.5357 Remote Similarity NPC206737
0.5357 Remote Similarity NPC289258
0.5357 Remote Similarity NPC611061
0.5306 Remote Similarity NPC283114
0.5306 Remote Similarity NPC207702
0.5306 Remote Similarity NPC149008
0.5286 Remote Similarity NPC471181
0.5273 Remote Similarity NPC214853
0.5231 Remote Similarity NPC471183
0.5224 Remote Similarity NPC469474
0.5091 Remote Similarity NPC469659
0.5091 Remote Similarity NPC475868
0.5088 Remote Similarity NPC272566
0.5072 Remote Similarity NPC470916

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC46277 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