| Identification | Back Directory | [Name]
3-[(3-Methoxybenzoyl)aMino]-4-(4-Methyl-1-piperazinyl)benzoic Acid Methyl Ester | [CAS]
890190-22-4 | [Synonyms]
WDR5-0103
WDR50103, >98%
WD-Repeat Protein 5-0103
WD-REPEAT PROTEIN 5-0103;WDR5 0103;WDR50103
Methyl 3-(3-methoxybenzamido)-4-(4-methylpiperazin-1-yl)benzoate
3-[(3-Methoxybenzoyl)aMino]-4-(4-Methyl-1-piperazinyl)benzoic Acid Methyl Ester
Benzoic acid, 3-[(3-methoxybenzoyl)amino]-4-(4-methyl-1-piperazinyl)-, methyl ester | [Molecular Formula]
C21H25N3O4 | [MDL Number]
MFCD07086826 | [MOL File]
890190-22-4.mol | [Molecular Weight]
383.44 |
| Chemical Properties | Back Directory | [Boiling point ]
495.2±45.0 °C(Predicted) | [density ]
1.223±0.06 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,2-8°C | [solubility ]
DMSO: soluble10mg/mL, clear | [form ]
powder | [pka]
12.96±0.70(Predicted) | [color ]
white to beige |
| Hazard Information | Back Directory | [Description]
WD-repeat protein 5 (WDR5) is a scaffold protein commonly involved in the formation of nucleosome-modifying protein complexes with histones. For example, WDR5 is a component of a mixed-lineage leukemia (MLL) methyltransferase complex that targets histone 3. WDR5 can also be a component of histone acetyltransferase complexes and can directly bind methylated as well as unmodified histones. WDR5-0103 is a small molecule that binds a peptide-binding pocket on WDR5 (Kd = 450 nM), inhibiting the catalytic activity of the MLL core complex in vitro (IC50 = 39 μM). | [Uses]
3-[(3-Methoxybenzoyl)amino]-4-(4-methyl-1-piperazinyl)benzoic Acid Methyl Ester is an small molecule inhibitor of WDR5, an essential componet of the human trithorax-like famliy of SET1 methyltransferase complexes that carry out trimethylation of histone 3 Lys4. | [in vivo]
WDR5-0103 (2.5 mg/kg; intraperitoneal injection; once a day; for 3 days) can reduce the level of H3K4me3, improve cognitive deficits and restore synaptic function in P301S transgenic Tau mice[3].
WDR5-0103 (2.5 mg/kg; intraperitoneal injection; three times) can reduce the level of H3K4me3 in the prefrontal cortex and improve cognitive function in 5xFAD mice[3]. | Animal Model: | P301S transgenic Tau mice (both male and female, 5-6 months old)[3] | | Dosage: | 2.5 mg/kg (dissolved in DMSO and diluted with saline, DMSO concentration of working solution < 0.2%) | | Administration: | Intraperitoneal injection, once a day, for 3 days | | Result: | In behavioral tests, the discrimination ratio in the novel object recognition test and the spatial memory index in the Barnes maze test were significantly improved, indicating the amelioration of cognitive deficits.
Western blot analysis showed that the decreased levels of synaptic GluR1, NR1, and NR2A subunits were remarkably restored.
|
| Animal Model: | 5xFAD mice (both male and female, 5-6 months old; transgenic mice carrying five familial AD mutations on human amyloid precursor protein and human presenilin 1, a model of Alzheimer's disease)[3] | | Dosage: | 2.5 mg/kg (dissolved in DMSO and diluted with saline, DMSO concentration of working solution < 0.2%) | | Administration: | Intraperitoneal injection, three times | | Result: | Reduced the level of H3K4me3 in the prefrontal cortex of 5xFAD mice. In behavioral tests, the discrimination ratio in the novel object recognition test and the spatial memory index in the Barnes maze test were significantly improved, indicating the improvement of cognitive function. |
| [storage]
Store at +4°C | [References]
[1] VALENTINA MIGLIORI Ernesto G Marina Mapelli. On WD40 proteins: propelling our knowledge of transcriptional control?[J]. Epigenetics, 2012, 7 8: 815-822. DOI: 10.4161/epi.21140
[2] ERNESTO GUCCIONE. Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive[J]. Nature, 2007, 449 7164: 933-937. DOI: 10.1038/nature06166
[3] SEBASTIáN GUELMAN. The double-histone-acetyltransferase complex ATAC is essential for mammalian development.[J]. Molecular and Cellular Biology, 2009, 29 5: 1176-1188. DOI: 10.1128/mcb.01599-08
[4] GUILLERMO SENISTERRA. Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5.[J]. Biochemical Journal, 2013, 449 1: 151-159. DOI: 10.1042/bj20121280
[5] TIM J WIGLE Robert A C. Drugging the human methylome: an emerging modality for reversible control of aberrant gene transcription[J]. Current Opinion in Chemical Biology, 2013, 17 3: Pages 369-378. DOI: 10.1016/j.cbpa.2013.03.035 |
|
| Company Name: |
J & K SCIENTIFIC LTD.
|
| Telephone: |
18210857532 18210857532 |
| Website: |
https://www.jkchemical.com |
| Company Name: |
D&C Chemicals
|
| Telephone: |
+86-21-58447131 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList16963/0_EN.htm |
|