Natural Product: NPC487678

Natural Product IDNPC487678
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ILQAMXSZIMZTFM-KSSFIOAISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132967537
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 ILQAMXSZIMZTFM-KSSFIOAISA-N
Standard InCHI InChI=1S/C22H26O6/c1-14(8-16-4-6-19(24)21(10-16)25-3)18(12-26-15(2)23)9-17-5-7-20-22(11-17)28-13-27-20/h4-7,10-11,14,18,24H,8-9,12-13H2,1-3H3/t14-,18-/m0/s1
SMILES C[C@@H](Cc1ccc(c(c1)OC)O)[C@@H](Cc1ccc2c(c1)OCO2)COC(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.17 Volume:   397.685
?
Van der Waals volume.
Dense:   0.971 LogP:   3.332
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.067
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.397
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   17.0
TPSA:   74.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.697 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.176 Fsp3:   0.409
MCE-18:   55.161
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.384 Fluc inhibitor:   0.23
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.016
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.31
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.305 Promiscuous compounds:   0.125

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.727 MDCK Permeability:   -4.464
Pgp-inhibitor:   0.952 Pgp-substrate:   0.009
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):   0.0
20% Bioavailability (F20%):   0.479 30% Bioavailability (F30%):   0.481
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.646
Plasma Protein Binding (PPB):   98.188% Volume Distribution (VD):   -0.156
Fu: 2.92%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.288
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.039 CYP1A2-substrate:   0.989
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.992
CYP2C9-inhibitor:   0.429 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.179 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.009 CYP2C8-inhibitor:   1.0
HLM stability:   0.957
?
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):  2.925 Half-life (T1/2):  0.924

ADMET: Toxicity

hERG Blockers:  0.253 hERG Blockers (10um):  0.457
Human Hepatotoxicity (H-HT):  0.796 Drug-induced Liver Injury (DILI):  0.564
AMES Toxicity:  0.716 Rat Oral Acute Toxicity:  0.202
Maximum Recommended Daily Dose:  0.409 Skin Sensitization:  0.9
Carcinogencity:  0.361 Eye Corrosion:  0.009
Eye Irritation:  0.857 Respiratory Toxicity:  0.4
Drug-induced Neurotoxicity:  0.722 Ototoxicity:  0.434
Hematotoxicity:  0.44 Drug-induced Nephrotoxicity:  0.657
Genotoxicity:  0.619 RPMI-8226 Immunitoxicity:  0.133
A549 Cytotoxicity:  0.424 Hek293 Cytotoxicity:  0.508
BCF:   1.341
?
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:   4.043
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.267
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.863
?
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 = 73.1 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 87.0 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 80.2 % 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 NPC487678 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 NPC487679
0.8113 Intermediate Similarity NPC487680
0.7833 Intermediate Similarity NPC282291
0.7833 Intermediate Similarity NPC166137
0.7778 Intermediate Similarity NPC274356
0.7778 Intermediate Similarity NPC101748
0.7 Intermediate Similarity NPC487677
0.7 Intermediate Similarity NPC487675
0.6984 Remote Similarity NPC169973
0.6667 Remote Similarity NPC476748
0.6615 Remote Similarity NPC216223
0.6552 Remote Similarity NPC143895
0.6452 Remote Similarity NPC300776
0.6452 Remote Similarity NPC176814
0.6452 Remote Similarity NPC46880
0.6452 Remote Similarity NPC4982
0.6452 Remote Similarity NPC606629
0.6406 Remote Similarity NPC471505
0.6406 Remote Similarity NPC145569
0.6349 Remote Similarity NPC487681
0.625 Remote Similarity NPC106739
0.625 Remote Similarity NPC227217
0.625 Remote Similarity NPC117780
0.625 Remote Similarity NPC161249
0.6 Remote Similarity NPC68779
0.6 Remote Similarity NPC108598
0.5968 Remote Similarity NPC284464
0.5938 Remote Similarity NPC106920
0.5938 Remote Similarity NPC15811
0.5862 Remote Similarity NPC249788
0.5806 Remote Similarity NPC205915
0.5758 Remote Similarity NPC67247
0.5667 Remote Similarity NPC110958
0.5667 Remote Similarity NPC19890
0.5634 Remote Similarity NPC478703
0.5634 Remote Similarity NPC478704
0.5634 Remote Similarity NPC604694
0.5625 Remote Similarity NPC176586
0.5625 Remote Similarity NPC210354
0.5625 Remote Similarity NPC273657
0.5614 Remote Similarity NPC31344
0.5614 Remote Similarity NPC317769
0.5606 Remote Similarity NPC606339
0.5593 Remote Similarity NPC11453
0.5556 Remote Similarity NPC165133
0.5556 Remote Similarity NPC242885
0.5556 Remote Similarity NPC95614
0.5556 Remote Similarity NPC232316
0.5538 Remote Similarity NPC191158
0.5538 Remote Similarity NPC177644
0.5536 Remote Similarity NPC344161
0.5522 Remote Similarity NPC610284
0.5455 Remote Similarity NPC110699
0.5455 Remote Similarity NPC106055
0.5441 Remote Similarity NPC31751
0.5439 Remote Similarity NPC600801
0.5429 Remote Similarity NPC487682
0.541 Remote Similarity NPC192255
0.537 Remote Similarity NPC80241
0.537 Remote Similarity NPC301641
0.537 Remote Similarity NPC485483
0.5362 Remote Similarity NPC56184
0.5312 Remote Similarity NPC275950
0.5294 Remote Similarity NPC485282
0.5294 Remote Similarity NPC485283
0.5294 Remote Similarity NPC485281
0.5246 Remote Similarity NPC607444
0.5238 Remote Similarity NPC158737
0.5238 Remote Similarity NPC173308
0.5238 Remote Similarity NPC181079
0.5161 Remote Similarity NPC485480
0.5152 Remote Similarity NPC18576
0.5147 Remote Similarity NPC293757
0.5147 Remote Similarity NPC668
0.5079 Remote Similarity NPC171550
0.5079 Remote Similarity NPC134764
0.5077 Remote Similarity NPC28398
0.5075 Remote Similarity NPC88640
0.5075 Remote Similarity NPC185908
0.5075 Remote Similarity NPC101153
0.5075 Remote Similarity NPC193666
0.5075 Remote Similarity NPC123526
0.5075 Remote Similarity NPC482891
0.5075 Remote Similarity NPC608725
0.507 Remote Similarity NPC608199

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC487678 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