Natural Product: NPC45218

Natural Product IDNPC45218
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Bruceolide
IUPAC Name n.a.
Synonyms Bruceolide
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL140588
PubChem CID 99531
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0002119] Quassinoids

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 YLWQKYSDNGHLAO-PWRINDRCSA-N
Standard InCHI InChI=1S/C21H26O10/c1-7-8-4-10-20-6-30-21(18(28)29-3,15(20)13(25)17(27)31-10)16(26)12(24)14(20)19(8,2)5-9(22)11(7)23/h8,10,12-16,23-26H,4-6H2,1-3H3/t8-,10+,12+,13+,14+,15+,16-,19-,20+,21-/m0/s1
SMILES CC1=C(C(=O)C[C@@]2(C)[C@H]1C[C@@H]1[C@]34CO[C@@]([C@@H]4[C@H](C(=O)O1)O)([C@H]([C@@H]([C@H]23)O)O)C(=O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   438.15 Volume:   406.346
?
Van der Waals volume.
Dense:   1.078 LogP:   -0.515
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.307
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.872
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   26.0
TPSA:   159.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   4.0 Rings:   5.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.374 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.471 Fsp3:   0.762
MCE-18:   133.297
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.435 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.016
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.112 Promiscuous compounds:   0.216

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.875 MDCK Permeability:   -5.205
Pgp-inhibitor:   0.038 Pgp-substrate:   0.569
PAMPA:   0.991
?
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):   0.152
20% Bioavailability (F20%):   0.188 30% Bioavailability (F30%):   0.809
50% Bioavailability (F50%):   0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.013 MRP1:   0.986
Plasma Protein Binding (PPB):   33.783% Volume Distribution (VD):   -0.421
Fu: 66.111%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.098
BSEP inhibitor:   0.371

ADMET: Metabolism

CYP1A2-inhibitor:   0.323 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.011 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.012
CYP3A4-inhibitor:   0.439 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.005
HLM stability:   0.085
?
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):  1.905 Half-life (T1/2):  3.767

ADMET: Toxicity

hERG Blockers:  0.007 hERG Blockers (10um):  0.03
Human Hepatotoxicity (H-HT):  0.56 Drug-induced Liver Injury (DILI):  0.962
AMES Toxicity:  0.602 Rat Oral Acute Toxicity:  0.465
Maximum Recommended Daily Dose:  0.335 Skin Sensitization:  0.994
Carcinogencity:  0.115 Eye Corrosion:  0.004
Eye Irritation:  0.759 Respiratory Toxicity:  0.763
Drug-induced Neurotoxicity:  0.15 Ototoxicity:  0.712
Hematotoxicity:  0.395 Drug-induced Nephrotoxicity:  0.855
Genotoxicity:  0.786 RPMI-8226 Immunitoxicity:  0.152
A549 Cytotoxicity:  0.084 Hek293 Cytotoxicity:  0.054
BCF:   0.473
?
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:   3.2
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.886
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.997
?
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
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. seed n.a. DOI[10.1016/0031-9422(96)00258-0]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. fruit n.a. DOI[10.1016/S1383-5769(99)00023-9]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[10086989]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[1512598]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota Seeds n.a. n.a. PMID[15165151]
NPO15520 Dracocephalum kotschyi Species Lamiaceae Eukaryota n.a. leaf n.a. PMID[15949825]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota fruit Indonesia n.a. PMID[17896817]
NPO15146 Myrica nana Species Myricaceae Eukaryota n.a. n.a. n.a. PMID[18723353]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. Vietnam n.a. PMID[19026551]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota seeds n.a. n.a. PMID[20050684]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota Seeds n.a. n.a. PMID[22506620]
NPO15520 Dracocephalum kotschyi Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[26522747]
NPO15520 Dracocephalum kotschyi Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[29873264]
NPO15520 Dracocephalum kotschyi Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[33172599]
NPO15520 Dracocephalum kotschyi Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36253818]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[6481366]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[7561896]
NPO211 Aplysina cauliformis Species Aplysinidae Eukaryota n.a. n.a. n.a. PMID[8350091]
NPO2696 Brucea sumatrana Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO1641 Amycolatopsis azurea Species Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15520 Dracocephalum kotschyi Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12089 Trifolium alexandrinum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14150 Solanum jamaicense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12944 Sideritis tragoriganum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11637 Psilostrophe cooperi Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14528 Pneumatospora obcoronata n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO12717 Parmelia metastrigosa Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11873 Oecophylla smaragdina Species Formicidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15146 Myrica nana Species Myricaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14749 Lippia carviodora Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3164 Yponomeuta malinellus Species Yponomeutidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26718 Chelidonura fulvipunctata Species Aglajidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14845 Ceratophyllum submersum Species Ceratophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9203 Cephalonomia gallicola Species Bethylidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11432 Centrolobium tomentosum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5303 Castanea crenata Species Fagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10818 Carpobrotus edulis Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11084 Asplenium normale Species Aspleniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO211 Aplysina cauliformis Species Aplysinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15520 Dracocephalum kotschyi Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15520 Dracocephalum kotschyi Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12089 Trifolium alexandrinum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15146 Myrica nana Species Myricaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14749 Lippia carviodora Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11637 Psilostrophe cooperi Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5303 Castanea crenata Species Fagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14528 Pneumatospora obcoronata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO14845 Ceratophyllum submersum Species Ceratophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14948 Brucea javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1641 Amycolatopsis azurea Species Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO12089 Trifolium alexandrinum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11873 Oecophylla smaragdina Species Formicidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO211 Aplysina cauliformis Species Aplysinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11432 Centrolobium tomentosum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12717 Parmelia metastrigosa Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9203 Cephalonomia gallicola Species Bethylidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26718 Chelidonura fulvipunctata Species Aglajidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11084 Asplenium normale Species Aspleniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14150 Solanum jamaicense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15520 Dracocephalum kotschyi Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12944 Sideritis tragoriganum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3164 Yponomeuta malinellus Species Yponomeutidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10818 Carpobrotus edulis Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2696 Brucea sumatrana Species Simaroubaceae 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
NPT1759 Cell line FM3A Mus musculus EC50 > 21000.0 nM PMID[9871598]
NPT1759 Cell line FM3A Mus musculus Ratio > 12.3 n.a. PMID[9871598]
NPT1759 Cell line FM3A Mus musculus Viability = 100.0 % PMID[9871598]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum EC50 = 1700.0 nM PMID[9871598]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum ED50 = 75.2 ng/ml PMID[3325613]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus ED50 = 1.1 mg.kg-1 PMID[12570385]





 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 NPC45218 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 NPC268238
0.7286 Intermediate Similarity NPC143268
0.7083 Intermediate Similarity NPC323821
0.6986 Remote Similarity NPC16081
0.68 Remote Similarity NPC18945
0.68 Remote Similarity NPC152301
0.6538 Remote Similarity NPC265557
0.6456 Remote Similarity NPC476729
0.642 Remote Similarity NPC105926

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC45218 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