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BioAssay: AID 646011

Binding affinity to GST-tagged human recombinant SHP at 200 uM by NMR spectroscopy

The parent phenol of adapalene and its (E)-cinnamic acid analogue were found to induce cancer cell apoptosis but cause adverse systemic effects when administered to mice. In contrast, their respective 5-Cl- and 3-Cl-substituted analogues had their adverse effects mitigated without a comparable loss of cancer cell inhibitory activity. As a result, pharmacologic space in this region of the cinnamic more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Inactive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 646011
Data Source: ChEMBL (803459)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2013-11-17

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=Nuclear receptor subfamily 0 group B member 2; AltName: Full=Orphan nuclear receptor SHP; AltName: Full=Small heterodimer partner
Description ..   
Protein Family: The ligand binding domain of DAX1 protein, a nuclear receptor lacking DNA binding domain
Comment ..   

Gene:NR0B2     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: Analogues of orphan nuclear receptor small heterodimer partner ligand and apoptosis inducer (E)-4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid. 2. Impact of 3-chloro group replacement on inhibition of proliferation and induction of apoptosis of leukemia and cancer cell lines.

Abstract: The parent phenol of adapalene and its (E)-cinnamic acid analogue were found to induce cancer cell apoptosis but cause adverse systemic effects when administered to mice. In contrast, their respective 5-Cl- and 3-Cl-substituted analogues had their adverse effects mitigated without a comparable loss of cancer cell inhibitory activity. As a result, pharmacologic space in this region of the cinnamic phenyl ring scaffold was explored. Various substituents were introduced, and their effects on cancer cell proliferation and viability were evaluated. Cinnamic acids having 3-Br, CN, NO(2), NH(2), OMe, and N(3) groups had activity comparable to that of 4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-chlorocinnamic acid. A comparative molecular field analysis study indicated that introduction of an H-bond acceptor at position 3 of the central phenyl ring would favor inhibition of leukemia cell viability, and docking suggested its hydrogen bonding with a polar group in a small heterodimer partner homology model. The 3-CN, NO(2), NH(2), and OH analogues also inhibited MMTV-Wnt1 murine mammary stem cell viability.
(PMID: 22136251)
Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 101029

ChEMBL Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat
5Activity standard valueActivity standard valueFloat

Data Table (Concise)
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