| Identification | Back Directory | [Name]
ASTX-029 | [CAS]
2095719-92-7 | [Synonyms]
ASTX-029
(R)-2-(6-(5-chloro-2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-1-oxoisoindolin-2-yl)-N-((S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl)propanamide
2H-Isoindole-2-acetamide, 6-[5-chloro-2-[(tetrahydro-2H-pyran-4-yl)amino]-4-pyrimidinyl]-N-[(1S)-1-(3-fluoro-5-methoxyphenyl)-2-hydroxyethyl]-1,3-dihydro-α-methyl-1-oxo-, (αR)- | [Molecular Formula]
C29H31ClFN5O5 | [MDL Number]
MFCD32874105 | [MOL File]
2095719-92-7.mol | [Molecular Weight]
584.04 |
| Chemical Properties | Back Directory | [density ]
1.387±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 250 mg/mL (428.05 mM) | [form ]
A crystalline solid | [pka]
13.39±0.46(Predicted) | [color ]
White to off-white | [InChIKey]
BVRGQPJKSKKGIH-YZMAQOALNA-N | [SMILES]
O=C1N(CC2=CC=C(C3C(=CN=C(NC4CCOCC4)N=3)Cl)C=C12)[C@H](C)C(=O)N[C@@H](C1C=C(F)C=C(OC)C=1)CO |&1:24,29,r| |
| Hazard Information | Back Directory | [Description]
ASTX-029 is a highly potent and selective dual-mechanism ERK inhibitor discovered using fragment-based drug design. Because of its distinctive ERK-binding mode, ASTX-029 inhibits both ERK catalytic activity and the phosphorylation of ERK itself by MEK despite not directly inhibiting MEK activity. This dual mechanism was demonstrated in cell-free systems, cell lines and xenograft tumor tissue, where the phosphorylation of both ERK and its substrate, ribosomal S6 kinase (RSK), were modulated on treatment with ASTX-029. Markers of sensitivity were highlighted in a large cell panel, where ASTX-029 preferentially inhibited the proliferation of MAPK-activated cell lines, including those with BRAF or RAS mutations[1].
| [Chemical Properties]
White to off-white Solid | [Uses]
ASTX-029 is an orally bioavailable extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor. ASTX029 has the potential to potentially enhance anti-tumour activity in a wide range of tumour types, either as a single agent or in combination with other therapies. ASTX029 is currently in clinical studies for the treatment of relapsed/refractory solid tumours, including non-small cell lung cancer, melanoma, pancreatic cancer and colorectal cancer. Especially in KRAS-mutated NSCLC. | [in vivo]
In vivo, significant antitumor activity was observed in MAPK-activated tumor xenograft models following oral treatment. ASTX-029 also demonstrated activity in both in vitro and in vivo models of acquired resistance to MAPK pathway inhibitors.
| [IC 50]
2.7 nM | [References]
[1] Munck, Joanne M. et al. “Supplementary Figures 1-7 from ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK.” 2023. 0.
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| Company Name: |
DC Chemicals
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| Tel: |
021-58447131 13564518121 |
| Website: |
http://www.approvedhomemanagement.com/ShowSupplierProductsList927327/0.htm |
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