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| CC-90003 Basic information |
Product Name: | CC-90003 | Synonyms: | CC-90003;2-Propenamide, N-[2-[[2-[(2-methoxy-5-methyl-4-pyridinyl)amino]-5-(trifluoromethyl)-4-pyrimidinyl]amino]-5-methylphenyl]-;Inhibitor,Extracellular signal regulated kinases,ERK,inhibit,CC90003,CC 90003,CC-90003 | CAS: | 1621999-82-3 | MF: | C22H21F3N6O2 | MW: | 458.44 | EINECS: | | Product Categories: | | Mol File: | 1621999-82-3.mol | ![CC-90003 Structure](CAS/20200515/GIF/1621999-82-3.gif) |
| CC-90003 Chemical Properties |
storage temp. | Store at -20°C | solubility | DMSO : ≥ 125 mg/mL (272.66 mM);Water : < 0.1 mg/mL (insoluble) | form | Solid | color | White to off-white |
| CC-90003 Usage And Synthesis |
Biological Activity | CC-90003 is an irreversible inhibitor of ERK1/2 with IC50 of 10-20 nM and good kinase selectivity. | in vitro | CC-90003 potently inhibited the kinase activities of ERK1 and ERK2 in biochemical assays, cellular assays and mass spectrometry analysis of 347 kinases with IC50 at 10-20 nM quality, with Good kinase selectivity. In a kinase library containing 258 kinases, it has less than 50% inhibition on 213 kinases, moderate inhibitory activity (50%-80% inhibition) on 28 kinases, and significant inhibitory activity on 17 kinases Inhibition (>80%). Kinase screen in melanoma cell line A375 cells with BRAF V600E mutation, only 5 of 194 kinases (ERK1, ERK2, MKK4, MKK6 and FAK) were significantly inhibited (>80%) by 1 mM CC-90003 . However, the same concentration had no significant inhibitory activity (<14%) on 40 non-kinase enzymes and receptors. By iterative analysis, in cells, in addition to ERK1/2, only three kinases were inhibited by it at biologically relevant concentrations: KDR, FLT3 and PDGFRa. Tumor cells with BRAF mutations are particularly sensitive to it. In most, but not all, cases, it was toxic to KRAS-mutated PDAC, lung and colon cancer cell lines. It did not significantly inhibit the proliferation of normal lung fibroblasts or airway epithelial cells. | in vivo | In the HCT-116 xenograft in vivo model, CC-90003 was well tolerated within a range (12.5 mg bid-100 mg qd), while 50 mpk bid and 75 mpk bid induced elicited in animals on days 6-18 of dosing die. Both once-daily and twice-daily dosing frequencies resulted in inhibition of tumor growth. It has antitumor activity in all three KRAS-mutated human xenograft models tested. | target | Target | Value | ERK1 () | ERK2 () |
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| CC-90003 Preparation Products And Raw materials |
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