| Identification | Back Directory | [Name]
1H-Indazole-4-carboxamide, N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-6-[6-[4-[2-[[3-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethoxy]-1-oxopropyl]amino]ethyl]-1-piperazinyl]-3-pyridinyl]-1-(1-methylethyl)- | [CAS]
2225938-86-1 | [Synonyms]
MS177
1H-Indazole-4-carboxamide, N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-6-[6-[4-[2-[[3-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethoxy]-1-oxopropyl]amino]ethyl]-1-piperazinyl]-3-pyridinyl]-1-(1-methylethyl)- | [Molecular Formula]
C48H55N11O8 | [MOL File]
2225938-86-1.mol | [Molecular Weight]
914.02 |
| Chemical Properties | Back Directory | [Boiling point ]
1203.6±65.0 °C(Predicted) | [density ]
1.44±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 2mg/mL, clear (Warmed) | [form ]
Solid | [pka]
10.74±0.40(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Description]
MS177 is an effective and fast-acting EZH2 degrader. MS177 is a PROTAC that consists of a CRBN ligand, linker, and a potent enzymatic EZH2 inhibitor C24 (C24 IC50): 12?nM). MS177 effectively depletes both canonical EZH2–PRC2 and noncanonical EZH2–cMyc complexes. MS177 induces leukaemia cell growth inhibition, apoptosis and cell cycle progression arrest. | [Uses]
MS177 is an effective and fast-acting EZH2 degrader. MS177 is a PROTAC that consists of a CRBN ligand, linker, and a potent enzymatic EZH2 inhibitor C24 (C24 IC50): 12?nM). MS177 effectively depletes both canonical EZH2–PRC2 and noncanonical EZH2–cMyc complexes. MS177 induces leukaemia cell growth inhibition, apoptosis and cell cycle progression arrest[1]. | [in vivo]
MS177 (100?mg/kg, i.p., BID for 6 days) represses tumor growth in PDX animal model of MLL-r AML, and in subcutaneously xenografted MLL-r leukaemia models[1].
MS177 (50 mg/kg, i.p.) achieves intraplasma concentrations about 1 μM in male Swiss Albino mice[1].
MS177 (100?mg/kg, i.p., BID for 6?days per week; and 200?mg/?kg, i.p. BID 3?days per week) is well tolerated and lacks apparent toxicity in mice[1].
| Animal Model: | PDX animal model of MLL-r AML[1] | | Dosage: | 100?mg/kg | | Administration: | Intraperitoneal injection (i.p.), BID for 6 days. | | Result: | Inhibited tumor growth and prolonged survival. |
| [IC 50]
EZH2 | [storage]
Store at -20°C | [References]
[1] Wang J, et al. EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis. Nat Cell Biol. 2022 Mar;24(3):384-399. DOI:10.1038/s41556-022-00850-x |
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| Company Name: |
DC Chemicals
|
| Tel: |
021-58447131 13564518121 |
| Website: |
www.chemicalbook.com/showsupplierproductslist927327/0_en.htm |
| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
| Company Name: |
Biorbyt Ltd.
|
| Tel: |
+44 (0)1223 859 353 |
| Website: |
http://www.biorbyt.com |
|