Natural Product: NPC487681

Natural Product IDNPC487681
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RRRLWEMDXHIDHR-CYBMUJFWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132967540
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds

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 RRRLWEMDXHIDHR-CYBMUJFWSA-N
Standard InCHI InChI=1S/C20H22O4/c1-13(8-15-4-6-17(21)19(10-15)22-3)14(2)9-16-5-7-18-20(11-16)24-12-23-18/h4-7,10-11,13,21H,2,8-9,12H2,1,3H3/t13-/m1/s1
SMILES C[C@H](Cc1ccc(c(c1)OC)O)C(=C)Cc1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.15 Volume:   345.512
?
Van der Waals volume.
Dense:   0.944 LogP:   3.166
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.104
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.845
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   47.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.812 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.893 Fsp3:   0.3
MCE-18:   52.308
?
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:   0.55 Fluc inhibitor:   0.098
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.02
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.089
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.478 Promiscuous compounds:   0.148

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.841 MDCK Permeability:   -4.698
Pgp-inhibitor:   0.933 Pgp-substrate:   0.004
PAMPA:   0.001
?
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%):   0.834 30% Bioavailability (F30%):   0.551
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.5
Plasma Protein Binding (PPB):   98.508% Volume Distribution (VD):   0.063
Fu: 1.635%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.988 BCRP inhibitor:   0.772
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.323 CYP1A2-substrate:   0.994
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   0.337 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.35 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.01 CYP2C8-inhibitor:   0.999
HLM stability:   0.876
?
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):  5.854 Half-life (T1/2):  0.747

ADMET: Toxicity

hERG Blockers:  0.242 hERG Blockers (10um):  0.576
Human Hepatotoxicity (H-HT):  0.701 Drug-induced Liver Injury (DILI):  0.37
AMES Toxicity:  0.636 Rat Oral Acute Toxicity:  0.538
Maximum Recommended Daily Dose:  0.758 Skin Sensitization:  0.856
Carcinogencity:  0.442 Eye Corrosion:  0.106
Eye Irritation:  0.921 Respiratory Toxicity:  0.692
Drug-induced Neurotoxicity:  0.785 Ototoxicity:  0.295
Hematotoxicity:  0.186 Drug-induced Nephrotoxicity:  0.518
Genotoxicity:  0.7 RPMI-8226 Immunitoxicity:  0.094
A549 Cytotoxicity:  0.218 Hek293 Cytotoxicity:  0.458
BCF:   1.896
?
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:   4.327
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.662
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.035
?
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 = 84.7 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity > 15.0 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 78.1 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 78.5 % 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 NPC487681 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
0.7547 Intermediate Similarity NPC274356
0.7547 Intermediate Similarity NPC101748
0.678 Remote Similarity NPC487677
0.678 Remote Similarity NPC487675
0.6349 Remote Similarity NPC487679
0.6349 Remote Similarity NPC487678
0.629 Remote Similarity NPC106739
0.629 Remote Similarity NPC161249
0.623 Remote Similarity NPC46880
0.6 Remote Similarity NPC227217
0.6 Remote Similarity NPC282291
0.6 Remote Similarity NPC117780
0.6 Remote Similarity NPC166137
0.6 Remote Similarity NPC169973
0.5938 Remote Similarity NPC471505
0.5738 Remote Similarity NPC284464
0.5614 Remote Similarity NPC249788
0.5517 Remote Similarity NPC607444
0.5283 Remote Similarity NPC165133
0.5283 Remote Similarity NPC242885
0.5283 Remote Similarity NPC95614
0.5283 Remote Similarity NPC232316
0.5273 Remote Similarity NPC344161
0.5167 Remote Similarity NPC603109
0.5094 Remote Similarity NPC80241
0.5094 Remote Similarity NPC301641
0.5094 Remote Similarity NPC485483

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC487681 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