Natural Product: NPC482119

Natural Product IDNPC482119
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QPSNNRDTFGWIGI-ZDUSSCGKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132525161
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] Flavanones

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 QPSNNRDTFGWIGI-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C16H12O5/c17-8-10-11(18)6-14-15(16(10)20)12(19)7-13(21-14)9-4-2-1-3-5-9/h1-6,8,13,18,20H,7H2/t13-/m0/s1
SMILES c1ccc(cc1)[C@@H]1CC(=O)c2c(cc(c(C=O)c2O)O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.07 Volume:   282.482
?
Van der Waals volume.
Dense:   1.006 LogP:   3.451
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.228
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.357
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   83.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.828 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.052 Fsp3:   0.125
MCE-18:   54.778
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.651 Fluc inhibitor:   0.747
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.312
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.433
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.488 Promiscuous compounds:   0.076

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.984 MDCK Permeability:   -4.766
Pgp-inhibitor:   0.998 Pgp-substrate:   0.013
PAMPA:   0.689
?
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):   0.01
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.712
50% Bioavailability (F50%):   0.952

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.85
Plasma Protein Binding (PPB):   97.808% Volume Distribution (VD):   0.096
Fu: 1.76%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.933
BSEP inhibitor:   0.982

ADMET: Metabolism

CYP1A2-inhibitor:   0.717 CYP1A2-substrate:   0.942
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.99
CYP2C9-inhibitor:   0.329 CYP2C9-substrate:   0.009
CYP2D6-inhibitor:   0.035 CYP2D6-substrate:   0.965
CYP3A4-inhibitor:   0.024 CYP3A4-substrate:   0.298
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.626
HLM stability:   0.982
?
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):  5.039 Half-life (T1/2):  1.024

ADMET: Toxicity

hERG Blockers:  0.063 hERG Blockers (10um):  0.478
Human Hepatotoxicity (H-HT):  0.67 Drug-induced Liver Injury (DILI):  0.288
AMES Toxicity:  0.601 Rat Oral Acute Toxicity:  0.456
Maximum Recommended Daily Dose:  0.573 Skin Sensitization:  0.915
Carcinogencity:  0.315 Eye Corrosion:  0.127
Eye Irritation:  0.998 Respiratory Toxicity:  0.308
Drug-induced Neurotoxicity:  0.774 Ototoxicity:  0.257
Hematotoxicity:  0.075 Drug-induced Nephrotoxicity:  0.504
Genotoxicity:  0.923 RPMI-8226 Immunitoxicity:  0.125
A549 Cytotoxicity:  0.504 Hek293 Cytotoxicity:  0.408
BCF:   1.515
?
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:   4.344
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.866
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.336
?
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
NPO40842 Eugenia rigida Species n.a. n.a. n.a. n.a. n.a. PMID[23547843]
NPO40842 Eugenia rigida Species n.a. n.a. n.a. n.a. n.a. PMID[27618204]
NPO40842 Eugenia rigida Species n.a. n.a. 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
NPT554 Organism Candida glabrata Candida glabrata MFC = 70.4 uM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 6700.0 nM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. MIC = 35200.0 nM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 33200.0 nM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 63200.0 nM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. MIC = 70400.0 nM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[27618204]

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 NPC482119 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
1.0 High Similarity NPC482120
0.7708 Intermediate Similarity NPC312391
0.7222 Intermediate Similarity NPC1089
0.68 Remote Similarity NPC243083
0.68 Remote Similarity NPC13768
0.68 Remote Similarity NPC287246
0.6607 Remote Similarity NPC39045
0.6538 Remote Similarity NPC110776
0.6471 Remote Similarity NPC204515
0.6346 Remote Similarity NPC150648
0.6226 Remote Similarity NPC255106
0.6226 Remote Similarity NPC194432
0.6226 Remote Similarity NPC235165
0.6226 Remote Similarity NPC324386
0.6154 Remote Similarity NPC482121
0.6154 Remote Similarity NPC270964
0.6038 Remote Similarity NPC37392
0.5926 Remote Similarity NPC215885
0.5833 Remote Similarity NPC470135
0.5769 Remote Similarity NPC265871
0.5769 Remote Similarity NPC205093
0.5741 Remote Similarity NPC177354
0.5714 Remote Similarity NPC2416
0.5714 Remote Similarity NPC271590
0.5667 Remote Similarity NPC175504
0.566 Remote Similarity NPC476480
0.566 Remote Similarity NPC213322
0.566 Remote Similarity NPC84585
0.5556 Remote Similarity NPC248372
0.5556 Remote Similarity NPC32441
0.5556 Remote Similarity NPC79943
0.55 Remote Similarity NPC109183
0.5484 Remote Similarity NPC125855
0.5362 Remote Similarity NPC97812
0.5362 Remote Similarity NPC600145
0.5362 Remote Similarity NPC605490
0.5362 Remote Similarity NPC605492
0.5357 Remote Similarity NPC274784
0.5357 Remote Similarity NPC99597
0.5357 Remote Similarity NPC20709
0.5357 Remote Similarity NPC110038
0.5323 Remote Similarity NPC176229
0.5286 Remote Similarity NPC316960
0.5286 Remote Similarity NPC317715
0.5286 Remote Similarity NPC78835
0.5286 Remote Similarity NPC148945
0.5286 Remote Similarity NPC309512
0.5286 Remote Similarity NPC204561
0.5273 Remote Similarity NPC6407
0.5273 Remote Similarity NPC482487
0.5273 Remote Similarity NPC545184
0.5263 Remote Similarity NPC476153
0.5224 Remote Similarity NPC228504
0.52 Remote Similarity NPC314329
0.52 Remote Similarity NPC603208
0.5161 Remote Similarity NPC95936
0.5152 Remote Similarity NPC35038
0.5147 Remote Similarity NPC64915
0.5098 Remote Similarity NPC228184
0.5091 Remote Similarity NPC182421
0.5088 Remote Similarity NPC300668
0.5088 Remote Similarity NPC107586
0.5088 Remote Similarity NPC329203
0.5088 Remote Similarity NPC222342
0.5082 Remote Similarity NPC76372
0.5082 Remote Similarity NPC37496
0.5079 Remote Similarity NPC470131
0.5079 Remote Similarity NPC470132
0.5072 Remote Similarity NPC488556

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482119 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
0.68 Remote Similarity NPD1550 Phase 2
0.5556 Remote Similarity NPD1552 Clinical (unspecified phase)
0.52 Remote Similarity NPD1547 Clinical (unspecified phase)

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