Natural Product: NPC482044

Natural Product IDNPC482044
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YFASDGOQOINOOM-SVJYBPAOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132967560
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives
          • [CHEMONTID:0003002] Hydroxycinnamic acid esters
            • [CHEMONTID:0000465] Coumaric acid esters

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 YFASDGOQOINOOM-SVJYBPAOSA-N
Standard InCHI InChI=1S/C19H24O3/c1-15(2)5-4-6-16(3)13-14-22-19(21)12-9-17-7-10-18(20)11-8-17/h5,7-13,20H,4,6,14H2,1-3H3/b12-9+,16-13-
SMILES CC(=CCC/C(=CCOC(=O)/C=C/c1ccc(cc1)O)/C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.17 Volume:   336.539
?
Van der Waals volume.
Dense:   0.892 LogP:   5.564
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.704
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.495
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   10.0
TPSA:   46.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.453 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.499 Fsp3:   0.316
MCE-18:   8.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.995 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.075
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.525
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.87 Promiscuous compounds:   0.164

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.85 MDCK Permeability:   -4.718
Pgp-inhibitor:   0.935 Pgp-substrate:   0.034
PAMPA:   0.084
?
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):   0.011
20% Bioavailability (F20%):   0.842 30% Bioavailability (F30%):   0.871
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.078 MRP1:   0.607
Plasma Protein Binding (PPB):   96.104% Volume Distribution (VD):   -0.055
Fu: 3.238%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.975 BCRP inhibitor:   0.097
BSEP inhibitor:   0.967

ADMET: Metabolism

CYP1A2-inhibitor:   0.006 CYP1A2-substrate:   0.932
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.632
CYP2C9-inhibitor:   0.008 CYP2C9-substrate:   0.777
CYP2D6-inhibitor:   0.67 CYP2D6-substrate:   0.95
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.854
?
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):  11.588 Half-life (T1/2):  0.899

ADMET: Toxicity

hERG Blockers:  0.168 hERG Blockers (10um):  0.586
Human Hepatotoxicity (H-HT):  0.494 Drug-induced Liver Injury (DILI):  0.128
AMES Toxicity:  0.274 Rat Oral Acute Toxicity:  0.059
Maximum Recommended Daily Dose:  0.316 Skin Sensitization:  0.998
Carcinogencity:  0.305 Eye Corrosion:  0.284
Eye Irritation:  0.983 Respiratory Toxicity:  0.298
Drug-induced Neurotoxicity:  0.641 Ototoxicity:  0.215
Hematotoxicity:  0.124 Drug-induced Nephrotoxicity:  0.375
Genotoxicity:  0.03 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.048 Hek293 Cytotoxicity:  0.215
BCF:   1.574
?
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:   4.737
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.154
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.795
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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
NPO40119 Eremophila longifolia Species Scrophulariaceae Eukaryota n.a. n.a. n.a. PMID[28257200]
NPO40119 Eremophila longifolia Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT71 Cell line HEK293 Homo sapiens CC50 = 273000.0 nM PMID[28257200]
NPT65 Cell line HepG2 Homo sapiens CC50 = 157000.0 nM PMID[28257200]
NPT1118 Organism Streptococcus pneumoniae Streptococcus pneumoniae MIC = 64.0 ug.mL-1 PMID[28257200]
NPT20 Organism Candida albicans Candida albicans MIC > 64.0 ug.mL-1 PMID[28257200]
NPT19 Organism Escherichia coli Escherichia coli MIC > 64.0 ug.mL-1 PMID[28257200]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 64.0 ug.mL-1 PMID[28257200]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans MIC >= 32.0 ug.mL-1 PMID[28257200]
NPT747 Organism Acinetobacter baumannii Acinetobacter baumannii MIC > 64.0 ug.mL-1 PMID[28257200]
NPT1531 Organism Enterococcus faecium Enterococcus faecium MIC = 8.0 ug.mL-1 PMID[28257200]

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 NPC482044 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
0.8039 Intermediate Similarity NPC482045
0.75 Intermediate Similarity NPC271641
0.7455 Intermediate Similarity NPC482043
0.6522 Remote Similarity NPC304638
0.64 Remote Similarity NPC261453
0.6078 Remote Similarity NPC260952
0.6078 Remote Similarity NPC82731
0.6038 Remote Similarity NPC273741
0.6038 Remote Similarity NPC608423
0.6038 Remote Similarity NPC611337
0.5714 Remote Similarity NPC204466
0.5532 Remote Similarity NPC253746
0.5397 Remote Similarity NPC139946
0.5306 Remote Similarity NPC171843
0.5217 Remote Similarity NPC47946
0.5217 Remote Similarity NPC26600
0.5185 Remote Similarity NPC33749
0.5172 Remote Similarity NPC157473
0.5172 Remote Similarity NPC151530
0.5098 Remote Similarity NPC95381
0.5077 Remote Similarity NPC294387

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482044 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