Natural Product: NPC603503

Natural Product IDNPC603503
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CQULNEWSZBPFNL-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3982563
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 CQULNEWSZBPFNL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O5/c1-20-11-5-3-10(4-6-11)13-9-22-15-8-16(21-2)14(18)7-12(15)17(13)19/h3-9,18H,1-2H3
SMILES COc1ccc(-c2coc3cc(OC)c(O)cc3c2=O)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.08 Volume:   299.778
?
Van der Waals volume.
Dense:   0.994 LogP:   2.329
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.603
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.09
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.804 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.06 Fsp3:   0.118
MCE-18:   17.0
?
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:   0.39 Fluc inhibitor:   0.994
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.971
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.62
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.453 Promiscuous compounds:   0.607

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.892 MDCK Permeability:   -4.692
Pgp-inhibitor:   0.071 Pgp-substrate:   0.031
PAMPA:   0.759
?
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):   0.71
20% Bioavailability (F20%):   0.446 30% Bioavailability (F30%):   0.387
50% Bioavailability (F50%):   0.897

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.73
Plasma Protein Binding (PPB):   90.493% Volume Distribution (VD):   -0.099
Fu: 11.517%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.967
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.674
BSEP inhibitor:   0.782

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.877
CYP2C9-inhibitor:   0.967 CYP2C9-substrate:   0.954
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.159
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.985
CYP2B6-substrate:   0.26 CYP2C8-inhibitor:   1.0
HLM stability:   0.007
?
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):  6.507 Half-life (T1/2):  1.061

ADMET: Toxicity

hERG Blockers:  0.229 hERG Blockers (10um):  0.576
Human Hepatotoxicity (H-HT):  0.483 Drug-induced Liver Injury (DILI):  0.841
AMES Toxicity:  0.619 Rat Oral Acute Toxicity:  0.5
Maximum Recommended Daily Dose:  0.66 Skin Sensitization:  0.255
Carcinogencity:  0.787 Eye Corrosion:  0.105
Eye Irritation:  0.963 Respiratory Toxicity:  0.815
Drug-induced Neurotoxicity:  0.533 Ototoxicity:  0.268
Hematotoxicity:  0.318 Drug-induced Nephrotoxicity:  0.423
Genotoxicity:  0.48 RPMI-8226 Immunitoxicity:  0.119
A549 Cytotoxicity:  0.198 Hek293 Cytotoxicity:  0.4
BCF:   1.13
?
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:   3.768
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.762
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.253
?
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
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1104/pp.84.1.73]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[12232319]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22208890]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18321 Medicago sativa Species Fabaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC = 4.0 uM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 n.a. n.a. n.a. PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC = 1.0 uM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC > 5.0 uM PMID[27100701]

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 NPC603503 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 NPC121522
0.7358 Intermediate Similarity NPC10467
0.6923 Remote Similarity NPC182428
0.6923 Remote Similarity NPC120924
0.6607 Remote Similarity NPC209560
0.6607 Remote Similarity NPC490700
0.6429 Remote Similarity NPC116632
0.6429 Remote Similarity NPC35763
0.6429 Remote Similarity NPC333691
0.6316 Remote Similarity NPC181124
0.6316 Remote Similarity NPC186507
0.6316 Remote Similarity NPC136095
0.6316 Remote Similarity NPC69430
0.6316 Remote Similarity NPC124714
0.6207 Remote Similarity NPC181209
0.614 Remote Similarity NPC474340
0.6034 Remote Similarity NPC100971
0.6034 Remote Similarity NPC294409
0.6034 Remote Similarity NPC490701
0.6034 Remote Similarity NPC610981
0.6 Remote Similarity NPC100263
0.5965 Remote Similarity NPC474264
0.5965 Remote Similarity NPC605229
0.5893 Remote Similarity NPC223354
0.5806 Remote Similarity NPC254741
0.5738 Remote Similarity NPC80710
0.569 Remote Similarity NPC185607
0.5625 Remote Similarity NPC260640
0.5614 Remote Similarity NPC195919
0.5538 Remote Similarity NPC488135
0.5455 Remote Similarity NPC133400
0.541 Remote Similarity NPC209487
0.5397 Remote Similarity NPC134726
0.5333 Remote Similarity NPC479067
0.5323 Remote Similarity NPC12377
0.5323 Remote Similarity NPC139293
0.5323 Remote Similarity NPC264289
0.5246 Remote Similarity NPC162680
0.5246 Remote Similarity NPC303644
0.5238 Remote Similarity NPC487216
0.5238 Remote Similarity NPC12175
0.5238 Remote Similarity NPC139364
0.5238 Remote Similarity NPC194653
0.5238 Remote Similarity NPC220050
0.5238 Remote Similarity NPC602183
0.5224 Remote Similarity NPC249824
0.5224 Remote Similarity NPC193564
0.5224 Remote Similarity NPC40942
0.5161 Remote Similarity NPC471590
0.5161 Remote Similarity NPC487217
0.5161 Remote Similarity NPC148497
0.5156 Remote Similarity NPC114192
0.5156 Remote Similarity NPC603384
0.5139 Remote Similarity NPC45165
0.5139 Remote Similarity NPC135345
0.5085 Remote Similarity NPC608360
0.5082 Remote Similarity NPC269451
0.5068 Remote Similarity NPC478528

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603503 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
0.5333 Remote Similarity NPD2796 Phase 2

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