Natural Product: NPC603662

Natural Product IDNPC603662
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BSEYWXDBSOCPQP-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL148826
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 BSEYWXDBSOCPQP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O4/c1-10-7-13(18)17-14(19)9-15(21-16(17)8-10)11-3-5-12(20-2)6-4-11/h3-9,18H,1-2H3
SMILES COc1ccc(-c2cc(=O)c3c(O)cc(C)cc3o2)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   282.09 Volume:   290.988
?
Van der Waals volume.
Dense:   0.969 LogP:   3.848
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.107
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.008
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   59.67
?
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:   0.781 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.065 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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.63 Fluc inhibitor:   0.989
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.937
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.842
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.472 Promiscuous compounds:   0.298

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.793 MDCK Permeability:   -4.68
Pgp-inhibitor:   0.481 Pgp-substrate:   0.366
PAMPA:   0.271
?
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):   0.098
20% Bioavailability (F20%):   0.453 30% Bioavailability (F30%):   0.795
50% Bioavailability (F50%):   0.976

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.032 MRP1:   0.829
Plasma Protein Binding (PPB):   98.0% Volume Distribution (VD):   -0.244
Fu: 1.409%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.96
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.906
BSEP inhibitor:   0.919

ADMET: Metabolism

CYP1A2-inhibitor:   0.692 CYP1A2-substrate:   0.714
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.208
CYP2C9-inhibitor:   0.907 CYP2C9-substrate:   0.982
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.746
CYP3A4-inhibitor:   0.048 CYP3A4-substrate:   0.166
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.887
?
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):  6.027 Half-life (T1/2):  0.744

ADMET: Toxicity

hERG Blockers:  0.114 hERG Blockers (10um):  0.498
Human Hepatotoxicity (H-HT):  0.466 Drug-induced Liver Injury (DILI):  0.914
AMES Toxicity:  0.686 Rat Oral Acute Toxicity:  0.412
Maximum Recommended Daily Dose:  0.709 Skin Sensitization:  0.437
Carcinogencity:  0.831 Eye Corrosion:  0.436
Eye Irritation:  0.992 Respiratory Toxicity:  0.836
Drug-induced Neurotoxicity:  0.129 Ototoxicity:  0.112
Hematotoxicity:  0.207 Drug-induced Nephrotoxicity:  0.145
Genotoxicity:  0.762 RPMI-8226 Immunitoxicity:  0.085
A549 Cytotoxicity:  0.219 Hek293 Cytotoxicity:  0.424
BCF:   1.313
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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:   4.036
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.791
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.42
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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
NPO5827 Dalea tuberculata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5827 Dalea tuberculata 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
NPT1316 Individual protein Adenosine A2a receptor Rattus norvegicus pKi(uM) = -1.45 n.a. PMID[9438021]
NPT1316 Individual protein Adenosine A2a receptor Rattus norvegicus Ki = 28000.0 nM PMID[8576921]
NPT218 Individual protein Adenosine A3 receptor Homo sapiens Ki = 6700.0 nM PMID[8576921]
NPT1315 Individual protein Adenosine A1 receptor Rattus norvegicus pKi(uM) = -0.53 n.a. PMID[9438021]
NPT218 Individual protein Adenosine A3 receptor Homo sapiens pKi(uM) = -1.7 n.a. PMID[9438021]
NPT1315 Individual protein Adenosine A1 receptor Rattus norvegicus Ki = 3400.0 nM PMID[8576921]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC603662 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
0.7037 Intermediate Similarity NPC29353
0.6909 Remote Similarity NPC231772
0.6429 Remote Similarity NPC156222
0.6316 Remote Similarity NPC184136
0.6316 Remote Similarity NPC57030
0.6316 Remote Similarity NPC145379
0.614 Remote Similarity NPC52611
0.614 Remote Similarity NPC600177
0.5862 Remote Similarity NPC274327
0.5862 Remote Similarity NPC125887
0.5862 Remote Similarity NPC127447
0.5806 Remote Similarity NPC295036
0.5763 Remote Similarity NPC176775
0.5763 Remote Similarity NPC22519
0.5763 Remote Similarity NPC234133
0.5763 Remote Similarity NPC266597
0.5763 Remote Similarity NPC604085
0.5763 Remote Similarity NPC604462
0.5738 Remote Similarity NPC195202
0.5738 Remote Similarity NPC223579
0.5645 Remote Similarity NPC610914
0.5507 Remote Similarity NPC248739
0.55 Remote Similarity NPC18260
0.5484 Remote Similarity NPC52005
0.5484 Remote Similarity NPC12200
0.5439 Remote Similarity NPC604293
0.5429 Remote Similarity NPC150908
0.541 Remote Similarity NPC108406
0.541 Remote Similarity NPC78913
0.5352 Remote Similarity NPC303485
0.5352 Remote Similarity NPC158027
0.5345 Remote Similarity NPC101294
0.5345 Remote Similarity NPC2771
0.5278 Remote Similarity NPC14606
0.5278 Remote Similarity NPC186227
0.5254 Remote Similarity NPC14958
0.5246 Remote Similarity NPC33265
0.5246 Remote Similarity NPC48479
0.5246 Remote Similarity NPC483773
0.5211 Remote Similarity NPC601984
0.5205 Remote Similarity NPC121649
0.5167 Remote Similarity NPC293183
0.5161 Remote Similarity NPC256283
0.5156 Remote Similarity NPC137062
0.5147 Remote Similarity NPC470402
0.5135 Remote Similarity NPC18699
0.5135 Remote Similarity NPC95090
0.5135 Remote Similarity NPC27408
0.5135 Remote Similarity NPC601565
0.5082 Remote Similarity NPC241498
0.5082 Remote Similarity NPC275722
0.5082 Remote Similarity NPC239128
0.5079 Remote Similarity NPC69394
0.5079 Remote Similarity NPC212678
0.5079 Remote Similarity NPC255350
0.5075 Remote Similarity NPC602829
0.5072 Remote Similarity NPC183
0.5067 Remote Similarity NPC181712

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603662 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
0.5079 Remote Similarity NPD2801 Pre-clinical

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