Natural Product: NPC604293

Natural Product IDNPC604293
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LGTXUFBDCDFQIU-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL16442
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 LGTXUFBDCDFQIU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O4/c1-19-12-5-3-11(4-6-12)16-10-15(18)14-8-7-13(20-2)9-17(14)21-16/h3-10H,1-2H3
SMILES COc1ccc(-c2cc(=O)c3ccc(OC)cc3o2)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   282.09 Volume:   290.988
?
Van der Waals volume.
Dense:   0.969 LogP:   2.819
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.928
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.435
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   48.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.738 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.825 Fsp3:   0.118
MCE-18:   16.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.576 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.989
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.848
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.659 Promiscuous compounds:   0.782

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.561 MDCK Permeability:   -4.509
Pgp-inhibitor:   0.793 Pgp-substrate:   0.052
PAMPA:   0.078
?
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):   0.237
20% Bioavailability (F20%):   0.483 30% Bioavailability (F30%):   0.472
50% Bioavailability (F50%):   0.914

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.935
Plasma Protein Binding (PPB):   91.842% Volume Distribution (VD):   -0.189
Fu: 7.917%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.978
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   0.792 CYP2C19-substrate:   0.178
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.986
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.455
CYP2B6-substrate:   0.078 CYP2C8-inhibitor:   1.0
HLM stability:   0.939
?
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):  6.91 Half-life (T1/2):  0.744

ADMET: Toxicity

hERG Blockers:  0.192 hERG Blockers (10um):  0.416
Human Hepatotoxicity (H-HT):  0.423 Drug-induced Liver Injury (DILI):  0.929
AMES Toxicity:  0.717 Rat Oral Acute Toxicity:  0.344
Maximum Recommended Daily Dose:  0.73 Skin Sensitization:  0.136
Carcinogencity:  0.879 Eye Corrosion:  0.301
Eye Irritation:  0.974 Respiratory Toxicity:  0.795
Drug-induced Neurotoxicity:  0.402 Ototoxicity:  0.109
Hematotoxicity:  0.386 Drug-induced Nephrotoxicity:  0.326
Genotoxicity:  0.935 RPMI-8226 Immunitoxicity:  0.1
A549 Cytotoxicity:  0.118 Hek293 Cytotoxicity:  0.505
BCF:   1.4
?
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:   3.997
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.983
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.561
?
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
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[11599360]
NPO3895 Gynerium sagittatum Species Poaceae Eukaryota n.a. n.a. n.a. PMID[17442349]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. seed n.a. PMID[21381697]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[37120447]
NPO63289 Virola carinata Genus Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3895 Gynerium sagittatum Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3895 Gynerium sagittatum Species Poaceae 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
NPT261 Individual protein Monoamine oxidase A Homo sapiens Inhibition n.a. n.a. % PMID[20045650]
NPT3117 Individual protein Glutaminyl-peptide cyclotransferase Homo sapiens Inhibition n.a. n.a. % PMID[27061673]
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 87.07 % PMID[23571415]
NPT582 Individual protein Monoamine oxidase B Homo sapiens IC50 = 49720.0 nM PMID[20045650]
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 91.89 % PMID[23571415]
NPT581 Individual protein Cyclooxygenase-2 Mus musculus Inhibition = 84.2 % PMID[14980657]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT520 Cell line 3T3-L1 Mus musculus Activity = 3.4 % PMID[21493073]
NPT520 Cell line 3T3-L1 Mus musculus Activity = 6.3 % PMID[21493073]
NPT520 Cell line 3T3-L1 Mus musculus Activity = 1.2 % PMID[21493073]
NPT520 Cell line 3T3-L1 Mus musculus Activity = 4.3 % PMID[21493073]
NPT28438 Unchecked Unchecked n.a. Ratio IC50 > 2.0 n.a. PMID[20045650]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. deltaA = 0.17 n.a. PMID[20565070]

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 NPC604293 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
0.8444 Intermediate Similarity NPC284424
0.7917 Intermediate Similarity NPC113089
0.7755 Intermediate Similarity NPC250266
0.7292 Intermediate Similarity NPC2771
0.6731 Remote Similarity NPC266597
0.6731 Remote Similarity NPC600010
0.66 Remote Similarity NPC101294
0.6226 Remote Similarity NPC125887
0.6226 Remote Similarity NPC29353
0.6154 Remote Similarity NPC14958
0.6111 Remote Similarity NPC22519
0.6111 Remote Similarity NPC145379
0.6111 Remote Similarity NPC604085
0.6071 Remote Similarity NPC308451
0.5849 Remote Similarity NPC333230
0.5818 Remote Similarity NPC57030
0.5789 Remote Similarity NPC605336
0.5789 Remote Similarity NPC606525
0.5769 Remote Similarity NPC607644
0.566 Remote Similarity NPC182428
0.566 Remote Similarity NPC608197
0.5636 Remote Similarity NPC77955
0.5636 Remote Similarity NPC299923
0.5636 Remote Similarity NPC156222
0.5636 Remote Similarity NPC608264
0.5536 Remote Similarity NPC184136
0.5536 Remote Similarity NPC231772
0.5472 Remote Similarity NPC40818
0.5439 Remote Similarity NPC603662
0.537 Remote Similarity NPC299582
0.537 Remote Similarity NPC278556
0.537 Remote Similarity NPC483772
0.537 Remote Similarity NPC602026
0.5345 Remote Similarity NPC602344
0.5283 Remote Similarity NPC41721
0.5283 Remote Similarity NPC603362
0.5273 Remote Similarity NPC129680
0.5263 Remote Similarity NPC70853
0.5263 Remote Similarity NPC176775
0.5254 Remote Similarity NPC604422
0.5254 Remote Similarity NPC607642
0.5179 Remote Similarity NPC599976
0.5172 Remote Similarity NPC269652
0.5167 Remote Similarity NPC279930
0.5091 Remote Similarity NPC603094
0.5088 Remote Similarity NPC274327
0.5088 Remote Similarity NPC52611
0.5088 Remote Similarity NPC127447
0.5088 Remote Similarity NPC600177
0.5082 Remote Similarity NPC295036

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC604293 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