Page last updated: 2024-11-12

lbw242

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Description

LBW242: proapoptotic IAP inhibitor; low MW Smac (Second mitochondria-derived activator of caspases) mimetic; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID11503417
CHEMBL ID1950720
SCHEMBL ID2731929
MeSH IDM0513505

Synonyms (21)

Synonym
bdbm50364485
CHEMBL1950720 ,
SCHEMBL2731929
lbw242
867324-12-7
(s)-n-((s)-1-cyclohexyl-2-oxo-2-((3ar,7as)-6-phenethyloctahydro-1h-pyrrolo[2,3-c]pyridin-1-yl)ethyl)-2-(methylamino)propanamide
HY-15519
CS-0006862
lbw 242 [who-dd]
ng5dd6ua5d ,
(2s)-n-((1s)-1-cyclohexyl-2-((3ar,7as)-octahydro-6-(2-phenylethyl)-1h-pyrrolo(2,3-c)pyridin-1-yl)-2-oxoethyl)-2-(methylamino)propanamide
lbw-242
unii-ng5dd6ua5d
propanamide, n-((1s)-1-cyclohexyl-2-((3ar,7as)-octahydro-6-(2-phenylethyl)-1h-pyrrolo(2,3-c)pyridin-1-yl)-2-oxoethyl)-2-(methylamino)-, (2s)-
(2s)-n-[(1s)-2-[(3ar,7as)-6-(2-phenylethyl)-3,3a,4,5,7,7a-hexahydro-2h-pyrrolo[2,3-c]pyridin-1-yl]-1-cyclohexyl-2-oxoethyl]-2-(methylamino)propanamide
DTXSID701101698
(2s)-n-[(1s)-1-cyclohexyl-2-[(3ar,7as)-octahydro-6-(2-phenylethyl)-1h-pyrrolo[2,3-c]pyridin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide
EN300-24146077
(2s)-n-[(1s)-2-[(3ar,7as)-6-(2-phenylethyl)-octahydro-1h-pyrrolo[2,3-c]pyridin-1-yl]-1-cyclohexyl-2-oxoethyl]-2-(methylamino)propanamide
AKOS040741943
PD129576

Research Excerpts

Treatment

ExcerptReferenceRelevance
"Treatment with LBW242 sensitized human and murine neuroblastoma cells to chemotherapy-induced apoptosis, which was mediated by activation of both the intrinsic and extrinsic apoptosis pathways."( Smac mimetic LBW242 sensitizes XIAP-overexpressing neuroblastoma cells for TNF-α-independent apoptosis.
Eggert, A; Eschenburg, G; Hundsdoerfer, P; Lode, HN; Schramm, A, 2012
)
1.09

Compound-Compound Interactions

ExcerptReferenceRelevance
" Conventional chemotherapeutic agents combined with small-molecule IAP inhibitors (LCL161 or LBW242) showed a synergistic effect in MB cells."( Blockade of Inhibitors of Apoptosis Proteins in Combination with Conventional Chemotherapy Leads to Synergistic Antitumor Activity in Medulloblastoma and Cancer Stem-Like Cells.
Chen, SM; Hsieh, LL; Huang, SF; Li, YY; Lui, TN; Salazar, N; Tseng, YY; Tu, CH, 2016
)
0.65
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
E3 ubiquitin-protein ligase XIAPHomo sapiens (human)IC50 (µMol)0.64000.00750.62274.1000AID1124864; AID645166
Baculoviral IAP repeat-containing protein 2Homo sapiens (human)IC50 (µMol)0.02700.00040.31212.7200AID1124863
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
E3 ubiquitin-protein ligase XIAPHomo sapiens (human)Kd0.90000.02800.20510.9000AID645165
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (51)

Processvia Protein(s)Taxonomy
regulation of apoptotic processE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
DNA damage responseE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
negative regulation of tumor necrosis factor-mediated signaling pathwayE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
Wnt signaling pathwayE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
regulation of BMP signaling pathwayE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
positive regulation of protein ubiquitinationE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
positive regulation of type I interferon productionE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
regulation of cell population proliferationE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
defense response to bacteriumE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
negative regulation of apoptotic processE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
positive regulation of canonical NF-kappaB signal transductionE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
negative regulation of cysteine-type endopeptidase activity involved in apoptotic processE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
regulation of innate immune responseE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
positive regulation of JNK cascadeE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
regulation of inflammatory responseE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
neuron apoptotic processE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
copper ion homeostasisE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
regulation of apoptosis involved in tissue homeostasisE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathwayE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
nucleotide-binding oligomerization domain containing 1 signaling pathwayE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
nucleotide-binding oligomerization domain containing 2 signaling pathwayE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
protein K63-linked ubiquitinationE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
positive regulation of canonical Wnt signaling pathwayE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
inhibition of cysteine-type endopeptidase activityE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
positive regulation of protein linear polyubiquitinationE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
regulation of cell cycleE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
protein polyubiquitinationBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
response to hypoxiaBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
placenta developmentBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
apoptotic processBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
cell surface receptor signaling pathwayBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
canonical NF-kappaB signal transductionBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
tumor necrosis factor-mediated signaling pathwayBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of toll-like receptor signaling pathwayBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
non-canonical NF-kappaB signal transductionBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of RIG-I signaling pathwayBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of cell population proliferationBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of apoptotic processBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
negative regulation of apoptotic processBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
positive regulation of canonical NF-kappaB signal transductionBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of innate immune responseBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
response to ethanolBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of cell differentiationBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
positive regulation of DNA-templated transcriptionBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of inflammatory responseBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
response to cAMPBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of cell cycleBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of necroptotic processBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
necroptotic processBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathwayBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of non-canonical NF-kappaB signal transductionBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
negative regulation of ripoptosome assembly involved in necroptotic processBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
positive regulation of protein K63-linked ubiquitinationBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
positive regulation of protein K48-linked ubiquitinationBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
positive regulation of protein monoubiquitinationBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of cysteine-type endopeptidase activityBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
regulation of reactive oxygen species metabolic processBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
positive regulation of protein ubiquitinationBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
negative regulation of necroptotic processBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (16)

Processvia Protein(s)Taxonomy
ubiquitin-protein transferase activityE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
cysteine-type endopeptidase inhibitor activityE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
protein bindingE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
identical protein bindingE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
cysteine-type endopeptidase inhibitor activity involved in apoptotic processE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
metal ion bindingE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
endopeptidase regulator activityE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
ubiquitin protein ligase activityE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
protein serine/threonine kinase bindingE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
transcription coactivator activityBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
ubiquitin-protein transferase activityBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
protein bindingBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
zinc ion bindingBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
transferase activityBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
identical protein bindingBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
ubiquitin bindingBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
protein-containing complex bindingBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
protein-folding chaperone bindingBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
FBXO family protein bindingBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
ubiquitin protein ligase activityBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
cysteine-type endopeptidase inhibitor activity involved in apoptotic processBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (7)

Processvia Protein(s)Taxonomy
cytoplasmE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
nucleusE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
nucleoplasmE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
cytoplasmE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
cytosolE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
nucleusE3 ubiquitin-protein ligase XIAPHomo sapiens (human)
XY bodyBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
nucleusBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
cytoplasmBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
cytosolBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
cytoplasmic side of plasma membraneBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
CD40 receptor complexBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
nucleusBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
cytoplasmBaculoviral IAP repeat-containing protein 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (9)

Assay IDTitleYearJournalArticle
AID645165Binding affinity to GST-tagged BIR3 domain of XIAP by isothermal titration calorimetry2012Bioorganic & medicinal chemistry letters, Feb-15, Volume: 22, Issue:4
Discovery of aminopiperidine-based Smac mimetics as IAP antagonists.
AID1124864Inhibition of XIAP BIR3 domain (unknown origin) by fluorescence polarization assay2014Bioorganic & medicinal chemistry letters, Apr-01, Volume: 24, Issue:7
Structure-based design and synthesis of tricyclic IAP (Inhibitors of Apoptosis Proteins) inhibitors.
AID1124869Intrinsic clearance in human liver microsomes2014Bioorganic & medicinal chemistry letters, Apr-01, Volume: 24, Issue:7
Structure-based design and synthesis of tricyclic IAP (Inhibitors of Apoptosis Proteins) inhibitors.
AID645164Lipophilicity, log D of the compound2012Bioorganic & medicinal chemistry letters, Feb-15, Volume: 22, Issue:4
Discovery of aminopiperidine-based Smac mimetics as IAP antagonists.
AID1124867Aqueous solubility of the compound2014Bioorganic & medicinal chemistry letters, Apr-01, Volume: 24, Issue:7
Structure-based design and synthesis of tricyclic IAP (Inhibitors of Apoptosis Proteins) inhibitors.
AID1124868Lipophilicity, log D of the compound2014Bioorganic & medicinal chemistry letters, Apr-01, Volume: 24, Issue:7
Structure-based design and synthesis of tricyclic IAP (Inhibitors of Apoptosis Proteins) inhibitors.
AID1124866Percentage unbound in human plasma2014Bioorganic & medicinal chemistry letters, Apr-01, Volume: 24, Issue:7
Structure-based design and synthesis of tricyclic IAP (Inhibitors of Apoptosis Proteins) inhibitors.
AID1124863Inhibition of cIAP1 BIR3 domain (unknown origin) by fluorescence polarization assay2014Bioorganic & medicinal chemistry letters, Apr-01, Volume: 24, Issue:7
Structure-based design and synthesis of tricyclic IAP (Inhibitors of Apoptosis Proteins) inhibitors.
AID645166Antagonist activity at GST-tagged BIR3 domain of XIAP using AbuRPFK-5FAM after 20 mins by fluorescence polarization assay2012Bioorganic & medicinal chemistry letters, Feb-15, Volume: 22, Issue:4
Discovery of aminopiperidine-based Smac mimetics as IAP antagonists.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (14)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's3 (21.43)29.6817
2010's11 (78.57)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 17.31

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index17.31 (24.57)
Research Supply Index2.71 (2.92)
Research Growth Index4.83 (4.65)
Search Engine Demand Index10.37 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (17.31)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other14 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]