Natural Product: NPC487680

Natural Product IDNPC487680
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UGSKXORAENSVJJ-KSSFIOAISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132967539
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 UGSKXORAENSVJJ-KSSFIOAISA-N
Standard InCHI InChI=1S/C22H28O6/c1-14(9-16-5-7-19(24)21(11-16)26-3)18(13-28-15(2)23)10-17-6-8-20(25)22(12-17)27-4/h5-8,11-12,14,18,24-25H,9-10,13H2,1-4H3/t14-,18-/m0/s1
SMILES C[C@@H](Cc1ccc(c(c1)OC)O)[C@@H](Cc1ccc(c(c1)OC)O)COC(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   388.19 Volume:   406.241
?
Van der Waals volume.
Dense:   0.956 LogP:   2.501
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.465
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.253
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   13.0
TPSA:   85.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.637 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.125 Fsp3:   0.409
MCE-18:   30.0
?
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:   0.237 Fluc inhibitor:   0.01
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.01
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.321
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.456 Promiscuous compounds:   0.137

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.995 MDCK Permeability:   -4.611
Pgp-inhibitor:   0.785 Pgp-substrate:   0.19
PAMPA:   0.002
?
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):   0.002
20% Bioavailability (F20%):   0.924 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.661
Plasma Protein Binding (PPB):   90.634% Volume Distribution (VD):   -0.327
Fu: 10.119%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.919
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.784
CYP2C19-inhibitor:   0.996 CYP2C19-substrate:   0.98
CYP2C9-inhibitor:   0.053 CYP2C9-substrate:   0.88
CYP2D6-inhibitor:   0.035 CYP2D6-substrate:   0.866
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.989
?
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):  5.547 Half-life (T1/2):  1.165

ADMET: Toxicity

hERG Blockers:  0.222 hERG Blockers (10um):  0.698
Human Hepatotoxicity (H-HT):  0.495 Drug-induced Liver Injury (DILI):  0.131
AMES Toxicity:  0.544 Rat Oral Acute Toxicity:  0.062
Maximum Recommended Daily Dose:  0.07 Skin Sensitization:  0.978
Carcinogencity:  0.294 Eye Corrosion:  0.039
Eye Irritation:  0.977 Respiratory Toxicity:  0.011
Drug-induced Neurotoxicity:  0.2 Ototoxicity:  0.455
Hematotoxicity:  0.171 Drug-induced Nephrotoxicity:  0.471
Genotoxicity:  0.078 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.139 Hek293 Cytotoxicity:  0.348
BCF:   1.284
?
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:   3.997
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.198
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.73
?
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 > 15.0 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 74.1 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 83.2 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 81.0 % 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 NPC487680 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
0.8113 Intermediate Similarity NPC487679
0.8113 Intermediate Similarity NPC487678
0.72 Intermediate Similarity NPC68779
0.72 Intermediate Similarity NPC108598
0.6818 Remote Similarity NPC165133
0.6818 Remote Similarity NPC242885
0.6818 Remote Similarity NPC95614
0.6818 Remote Similarity NPC232316
0.6809 Remote Similarity NPC31344
0.6809 Remote Similarity NPC317769
0.6786 Remote Similarity NPC67247
0.6667 Remote Similarity NPC273657
0.6607 Remote Similarity NPC606339
0.6491 Remote Similarity NPC610284
0.6429 Remote Similarity NPC110699
0.6429 Remote Similarity NPC106920
0.6429 Remote Similarity NPC300776
0.6429 Remote Similarity NPC15811
0.6429 Remote Similarity NPC176814
0.6429 Remote Similarity NPC4982
0.6429 Remote Similarity NPC106055
0.6429 Remote Similarity NPC606629
0.6296 Remote Similarity NPC275950
0.6207 Remote Similarity NPC485282
0.6207 Remote Similarity NPC485283
0.6207 Remote Similarity NPC485281
0.62 Remote Similarity NPC227217
0.62 Remote Similarity NPC117780
0.6167 Remote Similarity NPC282291
0.6167 Remote Similarity NPC166137
0.6 Remote Similarity NPC56214
0.6 Remote Similarity NPC487676
0.5926 Remote Similarity NPC274356
0.5926 Remote Similarity NPC173308
0.5926 Remote Similarity NPC181079
0.5926 Remote Similarity NPC101748
0.5902 Remote Similarity NPC608199
0.5893 Remote Similarity NPC253481
0.5893 Remote Similarity NPC253722
0.5893 Remote Similarity NPC475875
0.5806 Remote Similarity NPC120852
0.5806 Remote Similarity NPC216223
0.5769 Remote Similarity NPC127587
0.5763 Remote Similarity NPC100675
0.5763 Remote Similarity NPC476345
0.5763 Remote Similarity NPC601691
0.5714 Remote Similarity NPC281780
0.569 Remote Similarity NPC102908
0.5556 Remote Similarity NPC156840
0.5538 Remote Similarity NPC478703
0.5538 Remote Similarity NPC478704
0.551 Remote Similarity NPC85488
0.551 Remote Similarity NPC603326
0.55 Remote Similarity NPC90431
0.5424 Remote Similarity NPC187998
0.5424 Remote Similarity NPC257582
0.5424 Remote Similarity NPC241522
0.5397 Remote Similarity NPC471988
0.5397 Remote Similarity NPC169973
0.5333 Remote Similarity NPC487677
0.5333 Remote Similarity NPC487675
0.5323 Remote Similarity NPC31751
0.5246 Remote Similarity NPC486558
0.5246 Remote Similarity NPC101624
0.5246 Remote Similarity NPC184938
0.5238 Remote Similarity NPC278961
0.5238 Remote Similarity NPC64201
0.5238 Remote Similarity NPC113680
0.5208 Remote Similarity NPC8547
0.5192 Remote Similarity NPC177291
0.5161 Remote Similarity NPC161249
0.5098 Remote Similarity NPC299406
0.5091 Remote Similarity NPC607444
0.5085 Remote Similarity NPC284464
0.5082 Remote Similarity NPC23646
0.5082 Remote Similarity NPC485397
0.5079 Remote Similarity NPC42300
0.5072 Remote Similarity NPC67467

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC487680 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