Natural Product: NPC487675

Natural Product IDNPC487675
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PNUBXVRACRFHEY-CZUORRHYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132967534
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001969] Dibenzylbutane lignans

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 PNUBXVRACRFHEY-CZUORRHYSA-N
Standard InCHI InChI=1S/C20H24O5/c1-13(7-14-4-6-18-20(10-14)25-12-24-18)16(11-21)8-15-3-5-17(22)19(9-15)23-2/h3-6,9-10,13,16,21-22H,7-8,11-12H2,1-2H3/t13-,16-/m1/s1
SMILES C[C@H](Cc1ccc2c(c1)OCO2)[C@H](Cc1ccc(c(c1)OC)O)CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.16 Volume:   356.939
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Van der Waals volume.
Dense:   0.964 LogP:   2.733
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.768
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.855
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   16.0
TPSA:   68.15
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.807 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.092 Fsp3:   0.4
MCE-18:   52.214
?
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:   0.485 Fluc inhibitor:   0.394
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.015
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.192
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.23 Promiscuous compounds:   0.265

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.938 MDCK Permeability:   -4.717
Pgp-inhibitor:   0.922 Pgp-substrate:   0.048
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):   0.001
20% Bioavailability (F20%):   0.788 30% Bioavailability (F30%):   0.349
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.022 MRP1:   0.506
Plasma Protein Binding (PPB):   95.744% Volume Distribution (VD):   -0.094
Fu: 4.518%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.98
OATP1B3 inhibitor:   0.881 BCRP inhibitor:   0.176
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.018 CYP1A2-substrate:   0.988
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.996
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.926 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.047 CYP2C8-inhibitor:   1.0
HLM stability:   0.864
?
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):  6.381 Half-life (T1/2):  1.154

ADMET: Toxicity

hERG Blockers:  0.201 hERG Blockers (10um):  0.399
Human Hepatotoxicity (H-HT):  0.841 Drug-induced Liver Injury (DILI):  0.543
AMES Toxicity:  0.517 Rat Oral Acute Toxicity:  0.143
Maximum Recommended Daily Dose:  0.236 Skin Sensitization:  0.908
Carcinogencity:  0.314 Eye Corrosion:  0.02
Eye Irritation:  0.926 Respiratory Toxicity:  0.544
Drug-induced Neurotoxicity:  0.606 Ototoxicity:  0.627
Hematotoxicity:  0.387 Drug-induced Nephrotoxicity:  0.556
Genotoxicity:  0.212 RPMI-8226 Immunitoxicity:  0.143
A549 Cytotoxicity:  0.489 Hek293 Cytotoxicity:  0.462
BCF:   1.464
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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:   3.835
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.279
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.507
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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
NPO40344 Schisandra bicolor var. tuberculata Strain Schisandraceae Eukaryota Fruits n.a. n.a. PMID[28333453]

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
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 70.8 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 84.2 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 83.6 % PMID[28333453]

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 NPC487675 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 NPC487677
0.84 Intermediate Similarity NPC274356
0.84 Intermediate Similarity NPC101748
0.7551 Intermediate Similarity NPC487676
0.7115 Intermediate Similarity NPC607444
0.7 Intermediate Similarity NPC487679
0.7 Intermediate Similarity NPC487678
0.6949 Remote Similarity NPC106739
0.6949 Remote Similarity NPC161249
0.6897 Remote Similarity NPC46880
0.678 Remote Similarity NPC487681
0.6731 Remote Similarity NPC227217
0.6731 Remote Similarity NPC117780
0.6557 Remote Similarity NPC471505
0.64 Remote Similarity NPC40352
0.64 Remote Similarity NPC85488
0.64 Remote Similarity NPC213711
0.6379 Remote Similarity NPC284464
0.6349 Remote Similarity NPC169973
0.6296 Remote Similarity NPC249788
0.6296 Remote Similarity NPC196937
0.6094 Remote Similarity NPC282291
0.6094 Remote Similarity NPC166137
0.6 Remote Similarity NPC165133
0.6 Remote Similarity NPC242885
0.6 Remote Similarity NPC95614
0.6 Remote Similarity NPC232316
0.5962 Remote Similarity NPC344161
0.58 Remote Similarity NPC80241
0.58 Remote Similarity NPC301641
0.58 Remote Similarity NPC485483
0.5517 Remote Similarity NPC485480
0.541 Remote Similarity NPC28398
0.5357 Remote Similarity NPC56214
0.5333 Remote Similarity NPC487680
0.5254 Remote Similarity NPC104077
0.5254 Remote Similarity NPC219671
0.5254 Remote Similarity NPC147616
0.5192 Remote Similarity NPC221049
0.5172 Remote Similarity NPC485482
0.5172 Remote Similarity NPC127587
0.5172 Remote Similarity NPC606623
0.5152 Remote Similarity NPC610284
0.5085 Remote Similarity NPC5428
0.5079 Remote Similarity NPC142547
0.5079 Remote Similarity NPC228469
0.5072 Remote Similarity NPC216223

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC487675 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