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| | ASTX-029 Basic information |
| Product Name: | ASTX-029 | | Synonyms: | ASTX-029;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)-;(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;ERK1/2 inhibitor 2(ASTX-029);ERK1/2 inhibitor 2;ERK-1/2 inhibitor 2,Extracellular signal regulated kinases,Inhibitor,ASTX 029,ERK1/2 inhibitor 2,inhibit,ERK;(2R)-2-[6-[5-chloro-2-(tetrahydropyran-4-ylamino)pyrimidin-4-yl]-1-oxo-isoindolin-2-yl]-N-[(1S)-1-(3-fluoro-5-methoxy-phenyl)-2-hydroxy-ethyl]propanamide;ERK1/2 inhibitor 2, 10 mM in DMSO | | CAS: | 2095719-92-7 | | MF: | C29H31ClFN5O5 | | MW: | 584.05 | | EINECS: | | | Product Categories: | | | Mol File: | 2095719-92-7.mol |  |
| | ASTX-029 Chemical Properties |
| 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| |
| | ASTX-029 Usage And Synthesis |
| 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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| | ASTX-029 Preparation Products And Raw materials |
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