Natural Product: NPC168710

Natural Product IDNPC168710
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FQGUIRNHNGZCNL-ZDUSSCGKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3426681
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives

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 FQGUIRNHNGZCNL-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C15H16O5/c1-9(2)13(20-17)8-11-12(18-3)6-4-10-5-7-14(16)19-15(10)11/h4-7,13,17H,1,8H2,2-3H3/t13-/m0/s1
SMILES OO[C@H](C(=C)C)Cc1c(OC)ccc2c1oc(=O)cc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   276.1 Volume:   279.016
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Van der Waals volume.
Dense:   0.99 LogP:   2.087
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.478
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.435
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   13.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.393 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.273 Fsp3:   0.267
MCE-18:   26.0
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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:   0.414 Fluc inhibitor:   0.138
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.987
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.29
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.234 Promiscuous compounds:   0.551

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.864 MDCK Permeability:   -4.612
Pgp-inhibitor:   0.003 Pgp-substrate:   0.0
PAMPA:   0.282
?
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):   0.001
20% Bioavailability (F20%):   0.371 30% Bioavailability (F30%):   0.487
50% Bioavailability (F50%):   0.542

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.955
Plasma Protein Binding (PPB):   93.682% Volume Distribution (VD):   0.219
Fu: 5.371%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.985
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.002
BSEP inhibitor:   0.936

ADMET: Metabolism

CYP1A2-inhibitor:   0.478 CYP1A2-substrate:   0.756
CYP2C19-inhibitor:   0.879 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.336 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.951 CYP2D6-substrate:   0.272
CYP3A4-inhibitor:   0.759 CYP3A4-substrate:   0.529
CYP2B6-substrate:   0.661 CYP2C8-inhibitor:   0.629
HLM stability:   0.936
?
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):  8.253 Half-life (T1/2):  0.906

ADMET: Toxicity

hERG Blockers:  0.153 hERG Blockers (10um):  0.223
Human Hepatotoxicity (H-HT):  0.849 Drug-induced Liver Injury (DILI):  0.99
AMES Toxicity:  0.972 Rat Oral Acute Toxicity:  0.592
Maximum Recommended Daily Dose:  0.747 Skin Sensitization:  0.959
Carcinogencity:  0.812 Eye Corrosion:  0.05
Eye Irritation:  0.819 Respiratory Toxicity:  0.461
Drug-induced Neurotoxicity:  0.595 Ototoxicity:  0.221
Hematotoxicity:  0.448 Drug-induced Nephrotoxicity:  0.355
Genotoxicity:  0.997 RPMI-8226 Immunitoxicity:  0.145
A549 Cytotoxicity:  0.059 Hek293 Cytotoxicity:  0.563
BCF:   1.351
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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:   3.901
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.517
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.927
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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
NPO33003 murraya alata Species Rutaceae Eukaryota leaves n.a. n.a. PMID[25621853]
NPO33003 murraya alata Species Rutaceae 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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 12400.0 nM PMID[19845338]

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 NPC168710 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
0.717 Intermediate Similarity NPC80170
0.6607 Remote Similarity NPC62366
0.6545 Remote Similarity NPC96286
0.6316 Remote Similarity NPC185066
0.6316 Remote Similarity NPC33986
0.625 Remote Similarity NPC55147
0.5932 Remote Similarity NPC199204
0.5862 Remote Similarity NPC50896
0.5862 Remote Similarity NPC326600
0.5862 Remote Similarity NPC610664
0.5789 Remote Similarity NPC175159
0.5781 Remote Similarity NPC479311
0.5763 Remote Similarity NPC188380
0.5763 Remote Similarity NPC224543
0.5593 Remote Similarity NPC122259
0.5469 Remote Similarity NPC472424
0.5469 Remote Similarity NPC281241
0.5455 Remote Similarity NPC55149
0.5455 Remote Similarity NPC260265
0.5397 Remote Similarity NPC479313
0.5385 Remote Similarity NPC479309
0.5373 Remote Similarity NPC129572
0.5373 Remote Similarity NPC479310
0.5362 Remote Similarity NPC484110
0.5333 Remote Similarity NPC104796
0.5333 Remote Similarity NPC229916
0.5294 Remote Similarity NPC485014
0.5231 Remote Similarity NPC26954
0.5231 Remote Similarity NPC38099
0.5217 Remote Similarity NPC485015
0.5167 Remote Similarity NPC472516
0.5167 Remote Similarity NPC271600
0.5152 Remote Similarity NPC479312
0.5139 Remote Similarity NPC87950
0.5072 Remote Similarity NPC479308

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC168710 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