Natural Product: NPC488505

Natural Product IDNPC488505
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JQQXEGDTERJIIO-OUJBWJOFSA-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]

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 JQQXEGDTERJIIO-OUJBWJOFSA-N
Standard InCHI InChI=1S/C14H16O5/c1-16-11-4-3-8(5-12(11)17-2)13-9-6-19-14(15)10(9)7-18-13/h3-5,9-10,13H,6-7H2,1-2H3/t9-,10-,13+/m0/s1
SMILES COc1ccc(cc1OC)[C@@H]1[C@H]2COC(=O)[C@H]2CO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   264.1 Volume:   258.436
?
Van der Waals volume.
Dense:   1.022 LogP:   1.196
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.637
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.666
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   16.0
TPSA:   53.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.775 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.413 Fsp3:   0.5
MCE-18:   55.619
?
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:   0.307 Fluc inhibitor:   0.615
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.027
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.054
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.395 Promiscuous compounds:   0.241

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.74 MDCK Permeability:   -4.635
Pgp-inhibitor:   0.129 Pgp-substrate:   0.245
PAMPA:   0.074
?
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):   0.015
20% Bioavailability (F20%):   0.143 30% Bioavailability (F30%):   0.239
50% Bioavailability (F50%):   0.409

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.038 MRP1:   0.771
Plasma Protein Binding (PPB):   70.446% Volume Distribution (VD):   0.026
Fu: 28.406%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.878
OATP1B3 inhibitor:   0.91 BCRP inhibitor:   0.069
BSEP inhibitor:   0.754

ADMET: Metabolism

CYP1A2-inhibitor:   0.715 CYP1A2-substrate:   0.052
CYP2C19-inhibitor:   0.977 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.024
CYP3A4-inhibitor:   0.923 CYP3A4-substrate:   0.046
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.555
HLM stability:   0.497
?
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):  3.503 Half-life (T1/2):  3.219

ADMET: Toxicity

hERG Blockers:  0.064 hERG Blockers (10um):  0.392
Human Hepatotoxicity (H-HT):  0.764 Drug-induced Liver Injury (DILI):  0.961
AMES Toxicity:  0.668 Rat Oral Acute Toxicity:  0.155
Maximum Recommended Daily Dose:  0.262 Skin Sensitization:  0.978
Carcinogencity:  0.735 Eye Corrosion:  0.488
Eye Irritation:  0.982 Respiratory Toxicity:  0.478
Drug-induced Neurotoxicity:  0.446 Ototoxicity:  0.514
Hematotoxicity:  0.698 Drug-induced Nephrotoxicity:  0.76
Genotoxicity:  0.806 RPMI-8226 Immunitoxicity:  0.079
A549 Cytotoxicity:  0.196 Hek293 Cytotoxicity:  0.221
BCF:   0.657
?
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:   3.325
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.556
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.036
?
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
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. PMID[17156960]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. PMID[26422318]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota Fruits n.a. n.a. PMID[28218000]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

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
NPT2740 Cell line Neutrophils n.a. IC50 = 5.6 ug.mL-1 PMID[28218000]
NPT2740 Cell line Neutrophils n.a. IC50 > 10.0 ug.mL-1 PMID[28218000]
NPT2740 Cell line Neutrophils n.a. Inhibition > 50.0 % PMID[28218000]

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 NPC488505 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
0.7727 Intermediate Similarity NPC209229
0.766 Intermediate Similarity NPC14022
0.766 Intermediate Similarity NPC601703
0.7143 Intermediate Similarity NPC121783
0.7143 Intermediate Similarity NPC34902
0.7143 Intermediate Similarity NPC18449
0.6667 Remote Similarity NPC610778
0.6531 Remote Similarity NPC27159
0.6531 Remote Similarity NPC186220
0.6522 Remote Similarity NPC222127
0.6522 Remote Similarity NPC82862
0.6383 Remote Similarity NPC606146
0.6122 Remote Similarity NPC227160
0.6122 Remote Similarity NPC82111
0.566 Remote Similarity NPC27843
0.566 Remote Similarity NPC7171
0.5593 Remote Similarity NPC40094
0.5536 Remote Similarity NPC483653
0.5306 Remote Similarity NPC171928
0.5306 Remote Similarity NPC158526
0.5306 Remote Similarity NPC129687
0.5306 Remote Similarity NPC33611
0.5306 Remote Similarity NPC16830
0.5306 Remote Similarity NPC100223
0.5283 Remote Similarity NPC189474
0.5263 Remote Similarity NPC474139
0.5217 Remote Similarity NPC216929
0.5217 Remote Similarity NPC312713
0.5217 Remote Similarity NPC126935
0.5217 Remote Similarity NPC65933
0.5217 Remote Similarity NPC57268
0.5217 Remote Similarity NPC172676
0.5147 Remote Similarity NPC473236
0.5079 Remote Similarity NPC308555

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488505 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