Natural Product: NPC487685

Natural Product IDNPC487685
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZLLYZKKZJSBUKU-VQHIELQLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003423] 7,7'-epoxylignans

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 ZLLYZKKZJSBUKU-VQHIELQLSA-N
Standard InCHI InChI=1S/C20H20O6/c1-11-14(8-21)20(13-3-5-16-18(7-13)25-10-23-16)26-19(11)12-2-4-15-17(6-12)24-9-22-15/h2-7,11,14,19-21H,8-10H2,1H3/t11-,14-,19-,20+/m1/s1
SMILES C[C@@H]1[C@@H](CO)[C@H](c2ccc3c(c2)OCO3)O[C@H]1c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.13 Volume:   348.616
?
Van der Waals volume.
Dense:   1.022 LogP:   2.617
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.782
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.393
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   25.0
TPSA:   66.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.911 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.703 Fsp3:   0.4
MCE-18:   85.714
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.598 Fluc inhibitor:   0.743
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.03
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.022
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.15 Promiscuous compounds:   0.229

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.049 MDCK Permeability:   -5.071
Pgp-inhibitor:   0.44 Pgp-substrate:   0.001
PAMPA:   0.354
?
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%):   0.017 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.34

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.999 MRP1:   0.598
Plasma Protein Binding (PPB):   93.811% Volume Distribution (VD):   0.275
Fu: 7.619%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.881
OATP1B3 inhibitor:   0.918 BCRP inhibitor:   0.009
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.894 CYP1A2-substrate:   0.951
CYP2C19-inhibitor:   0.987 CYP2C19-substrate:   0.079
CYP2C9-inhibitor:   0.829 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.996 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.09 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.064 CYP2C8-inhibitor:   0.003
HLM stability:   0.025
?
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):  3.521 Half-life (T1/2):  1.065

ADMET: Toxicity

hERG Blockers:  0.19 hERG Blockers (10um):  0.42
Human Hepatotoxicity (H-HT):  0.745 Drug-induced Liver Injury (DILI):  0.938
AMES Toxicity:  0.789 Rat Oral Acute Toxicity:  0.305
Maximum Recommended Daily Dose:  0.353 Skin Sensitization:  0.469
Carcinogencity:  0.924 Eye Corrosion:  0.01
Eye Irritation:  0.745 Respiratory Toxicity:  0.514
Drug-induced Neurotoxicity:  0.614 Ototoxicity:  0.414
Hematotoxicity:  0.552 Drug-induced Nephrotoxicity:  0.581
Genotoxicity:  0.848 RPMI-8226 Immunitoxicity:  0.125
A549 Cytotoxicity:  0.196 Hek293 Cytotoxicity:  0.517
BCF:   1.676
?
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:   3.776
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.081
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.845
?
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 = 87.3 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 94.3 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 71.3 % 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 NPC487685 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
0.7805 Intermediate Similarity NPC271208
0.7805 Intermediate Similarity NPC233224
0.7805 Intermediate Similarity NPC610263
0.7111 Intermediate Similarity NPC57119
0.7111 Intermediate Similarity NPC158471
0.7111 Intermediate Similarity NPC226862
0.6346 Remote Similarity NPC135777
0.6346 Remote Similarity NPC7744
0.6226 Remote Similarity NPC142547
0.6226 Remote Similarity NPC228469
0.6226 Remote Similarity NPC488984
0.6226 Remote Similarity NPC488985
0.617 Remote Similarity NPC480478
0.6 Remote Similarity NPC136750
0.6 Remote Similarity NPC266848
0.5965 Remote Similarity NPC179521
0.5862 Remote Similarity NPC302506
0.5862 Remote Similarity NPC241846
0.5862 Remote Similarity NPC93610
0.5714 Remote Similarity NPC47181
0.5625 Remote Similarity NPC171928
0.5625 Remote Similarity NPC158526
0.5625 Remote Similarity NPC129687
0.5625 Remote Similarity NPC33611
0.5625 Remote Similarity NPC16830
0.5625 Remote Similarity NPC100223
0.5556 Remote Similarity NPC216929
0.5556 Remote Similarity NPC312713
0.5556 Remote Similarity NPC126935
0.5556 Remote Similarity NPC65933
0.5556 Remote Similarity NPC57268
0.5556 Remote Similarity NPC172676
0.5439 Remote Similarity NPC166884
0.5439 Remote Similarity NPC141569
0.5439 Remote Similarity NPC477701
0.5345 Remote Similarity NPC287124
0.5333 Remote Similarity NPC600032
0.5323 Remote Similarity NPC487682
0.5273 Remote Similarity NPC165128
0.5208 Remote Similarity NPC40352
0.5208 Remote Similarity NPC31530
0.5208 Remote Similarity NPC213711
0.5192 Remote Similarity NPC227160
0.5192 Remote Similarity NPC82111
0.5192 Remote Similarity NPC483654
0.5179 Remote Similarity NPC469981
0.5152 Remote Similarity NPC226153
0.5102 Remote Similarity NPC50683
0.5102 Remote Similarity NPC72046
0.5102 Remote Similarity NPC261812
0.5102 Remote Similarity NPC112571
0.5102 Remote Similarity NPC65183
0.5102 Remote Similarity NPC285725
0.5098 Remote Similarity NPC137487
0.5088 Remote Similarity NPC101807
0.5075 Remote Similarity NPC304048

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC487685 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