Natural Product: NPC484113

Natural Product IDNPC484113
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SZBDAOSTNLHQSN-AZUAARDMSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0001722] Fatty alcohol 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 SZBDAOSTNLHQSN-AZUAARDMSA-N
Standard InCHI InChI=1S/C20H24O6/c1-11(2)10-16(22)26-20(18(23)12(3)4)17-14(24-5)8-6-13-7-9-15(21)25-19(13)17/h6-9,11,18,20,23H,3,10H2,1-2,4-5H3/t18-,20+/m0/s1
SMILES CC(C)CC(=O)O[C@H](c1c(ccc2ccc(=O)oc12)OC)[C@H](C(=C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.16 Volume:   371.649
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Van der Waals volume.
Dense:   0.969 LogP:   2.92
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.893
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.069
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   14.0
TPSA:   85.97
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.463 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.647 Fsp3:   0.4
MCE-18:   32.0
?
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:   0.748 Fluc inhibitor:   0.005
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.919
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.539
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.101 Promiscuous compounds:   0.089

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.764 MDCK Permeability:   -4.594
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   0.484
?
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):   0.0
20% Bioavailability (F20%):   0.236 30% Bioavailability (F30%):   0.206
50% Bioavailability (F50%):   0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.994
Plasma Protein Binding (PPB):   91.263% Volume Distribution (VD):   0.262
Fu: 7.753%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.919

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.292 CYP2C19-substrate:   0.853
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.461
CYP3A4-inhibitor:   0.931 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.987
HLM stability:   0.379
?
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):  7.296 Half-life (T1/2):  0.77

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.223
Human Hepatotoxicity (H-HT):  0.756 Drug-induced Liver Injury (DILI):  0.693
AMES Toxicity:  0.682 Rat Oral Acute Toxicity:  0.484
Maximum Recommended Daily Dose:  0.526 Skin Sensitization:  0.723
Carcinogencity:  0.59 Eye Corrosion:  0.091
Eye Irritation:  0.916 Respiratory Toxicity:  0.494
Drug-induced Neurotoxicity:  0.678 Ototoxicity:  0.343
Hematotoxicity:  0.499 Drug-induced Nephrotoxicity:  0.61
Genotoxicity:  0.948 RPMI-8226 Immunitoxicity:  0.198
A549 Cytotoxicity:  0.181 Hek293 Cytotoxicity:  0.206
BCF:   1.388
?
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:   4.067
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.561
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.104
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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
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. leaf n.a. PMID[24354205]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. twig n.a. PMID[24354205]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[29303577]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12182 Murraya exotica Species Rutaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT34 Cell line BV-2 Mus musculus IC50 = 26400.0 nM PMID[29303577]

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 NPC484113 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
0.7667 Intermediate Similarity NPC26954
0.7667 Intermediate Similarity NPC38099
0.6176 Remote Similarity NPC129572
0.6143 Remote Similarity NPC128529
0.6143 Remote Similarity NPC55615
0.6032 Remote Similarity NPC199204
0.6029 Remote Similarity NPC287286
0.6 Remote Similarity NPC153818
0.6 Remote Similarity NPC149320
0.6 Remote Similarity NPC160727
0.6 Remote Similarity NPC177281
0.6 Remote Similarity NPC232246
0.5968 Remote Similarity NPC50896
0.5968 Remote Similarity NPC326600
0.5775 Remote Similarity NPC312881
0.5652 Remote Similarity NPC484112
0.5526 Remote Similarity NPC283019
0.5342 Remote Similarity NPC485015
0.5286 Remote Similarity NPC479309
0.5278 Remote Similarity NPC166672
0.5231 Remote Similarity NPC229916
0.5231 Remote Similarity NPC610664
0.5217 Remote Similarity NPC167111
0.5217 Remote Similarity NPC318400
0.5152 Remote Similarity NPC62366
0.5152 Remote Similarity NPC185066
0.5068 Remote Similarity NPC86892
0.5068 Remote Similarity NPC471909
0.5067 Remote Similarity NPC476455
0.5067 Remote Similarity NPC484110

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC484113 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