Natural Product: NPC5633

Natural Product IDNPC5633
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HOPDFAWBFXSPSA-PJYBLOJUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 15658448
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 HOPDFAWBFXSPSA-PJYBLOJUSA-N
Standard InCHI InChI=1S/C22H24O7/c1-10-5-12-6-14-19(28-8-26-14)21(24-3)16(12)17-13(18(23)11(10)2)7-15-20(22(17)25-4)29-9-27-15/h6-7,10-11,18,23H,5,8-9H2,1-4H3/t10-,11-,18-/m1/s1
SMILES C[C@@H]1Cc2cc3c(c(c2-c2c(cc4c(c2OC)OCO4)[C@@H]([C@@H]1C)O)OC)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   400.15 Volume:   391.999
?
Van der Waals volume.
Dense:   1.021 LogP:   3.529
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.195
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.221
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   26.0
TPSA:   75.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.824 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.928 Fsp3:   0.455
MCE-18:   94.5
?
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:   0.841 Fluc inhibitor:   0.016
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.442
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.183
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.085 Promiscuous compounds:   0.286

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.988 MDCK Permeability:   -4.731
Pgp-inhibitor:   0.261 Pgp-substrate:   0.014
PAMPA:   0.264
?
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%):   0.034 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.318

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.935 MRP1:   0.985
Plasma Protein Binding (PPB):   96.713% Volume Distribution (VD):   0.043
Fu: 3.347%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.871
OATP1B3 inhibitor:   0.92 BCRP inhibitor:   0.002
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.779
CYP2C19-inhibitor:   0.976 CYP2C19-substrate:   0.687
CYP2C9-inhibitor:   0.98 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.992 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.041 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.042 CYP2C8-inhibitor:   0.0
HLM stability:   0.543
?
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):  4.24 Half-life (T1/2):  1.133

ADMET: Toxicity

hERG Blockers:  0.199 hERG Blockers (10um):  0.562
Human Hepatotoxicity (H-HT):  0.619 Drug-induced Liver Injury (DILI):  0.808
AMES Toxicity:  0.823 Rat Oral Acute Toxicity:  0.629
Maximum Recommended Daily Dose:  0.722 Skin Sensitization:  0.782
Carcinogencity:  0.948 Eye Corrosion:  0.001
Eye Irritation:  0.354 Respiratory Toxicity:  0.84
Drug-induced Neurotoxicity:  0.833 Ototoxicity:  0.463
Hematotoxicity:  0.816 Drug-induced Nephrotoxicity:  0.796
Genotoxicity:  0.886 RPMI-8226 Immunitoxicity:  0.279
A549 Cytotoxicity:  0.757 Hek293 Cytotoxicity:  0.688
BCF:   1.776
?
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:   3.672
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.199
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.213
?
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]
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]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8187 Schisandra chinensis 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]
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

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 NPC5633 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 NPC172171
1.0 High Similarity NPC239254
0.9583 High Similarity NPC230538
0.9583 High Similarity NPC229172
0.9583 High Similarity NPC103637
0.9583 High Similarity NPC36531
0.8 Intermediate Similarity NPC166506
0.8 Intermediate Similarity NPC110763
0.7931 Intermediate Similarity NPC473323
0.7797 Intermediate Similarity NPC473425
0.766 Intermediate Similarity NPC475868
0.7544 Intermediate Similarity NPC189239
0.7347 Intermediate Similarity NPC324962
0.7234 Intermediate Similarity NPC32189
0.6939 Remote Similarity NPC145722
0.6939 Remote Similarity NPC256776
0.6939 Remote Similarity NPC185680
0.6613 Remote Similarity NPC471180
0.6552 Remote Similarity NPC477381
0.6462 Remote Similarity NPC471181
0.6441 Remote Similarity NPC477879
0.6429 Remote Similarity NPC46277
0.6316 Remote Similarity NPC475865
0.6207 Remote Similarity NPC301765
0.6129 Remote Similarity NPC249070
0.6 Remote Similarity NPC473989
0.5965 Remote Similarity NPC53722
0.5965 Remote Similarity NPC201404
0.5965 Remote Similarity NPC290714
0.5862 Remote Similarity NPC133934
0.5806 Remote Similarity NPC325720
0.5806 Remote Similarity NPC316676
0.5763 Remote Similarity NPC220577
0.5667 Remote Similarity NPC304821
0.5577 Remote Similarity NPC87295
0.5538 Remote Similarity NPC312763
0.5484 Remote Similarity NPC76415
0.5484 Remote Similarity NPC218510
0.5373 Remote Similarity NPC24562
0.5357 Remote Similarity NPC156948
0.5306 Remote Similarity NPC283114
0.5306 Remote Similarity NPC207702
0.5306 Remote Similarity NPC149008
0.5231 Remote Similarity NPC85141
0.5224 Remote Similarity NPC149735
0.5172 Remote Similarity NPC86605
0.5082 Remote Similarity NPC184684
0.5082 Remote Similarity NPC184641
0.5075 Remote Similarity NPC154971

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC5633 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