Selumetinib, Free Base (AZD6244, ARRY-142886, ARRY-886, CAS 606143-52-6), >99%

LC Laboratories' Product Number S-4490 - Selumetinib, Free Base (AZD6244, ARRY-142886, ARRY-886, CAS 606143-52-6), >99% - for research use only. Selumetinib, also known as AZD6244, is a specific MEK1/2 inhibitor with an IC50 value of 14 nM against purified MEK1. Selumetinib inhibited the growth of primary hepatocellular carcinoma (HCC) cells in vitro and the growth of 7 HCC xenografts dose-dependently in vivo, possibly by inactivating ERK1/2 and p90RSK and up-regulating activated caspase-3, caspase-7 and cleaved poly(ADP)ribose polymerase. The combination of selumetinib and MK2206 at ratios of 8:1, 4:1, and 2:1 has a significant synergistic inhibitory effect on the growth of human non-small cell lung cancer in vitro and in vivo and improves the survival of mice bearing highly aggressive human lung tumors. Selumetinib and the mTOR inhibitor rapamycin had synergistic inhibitory effects on the growth of BxPC-3 and MIA PaCa-2 pancreatic cancers in vivo. Selumetinib also demonstrated a significant anti-angiogenic effect. When fractionated tumor-localized radiotherapy (5 x 2 Gy) was combined with selumetinib treatment, the growth delay of Calu-6 lung and colorectal tumor xenografts was enhanced significantly when compared with either treatment alone. The levels of phosphorylated AKT were significantly higher in resistant lung cancer cells than in the sensitive cells. Phosphorylated AKT can be used as a molecular biomarker to predict lung cancer response to MEK inhibitors. Selumetinib was cytostatic and inhibited the growth of melanoma cells in vitro. In vivo, selumetinib treatment decreased phospho-ERK in the 1205Lu melanoma tumors and significantly suppressed tumor growth in severe combined immunodeficient mice. But selumetinib monotherapy was largely only cytostatic because the original tumors remained viable. Combination treatment of selumetinib with docetaxel caused tumor regression. Selumetinib inhibited the growth of a spectrum of thyroid cancer cells by inhibiting the MEK-ERK pathway. However, the inhibitory effect was cytostatic in papillary thyroid cancer and anaplastic thyroid cancer cells bearing a BRAF mutation. Selumetinib may have less inhibitory impact on thyroid cancer cells lacking this mutation. Selumetinib induced myeloma-cell cytotoxicity and inhibited osteoclastogenesis, possibly by inhibiting MEK. Related CAS numbers: 943332-08-9 for the selumetinib sulfate. Another CAS number previously assigned to Selumetinib, Free Base, namely 865610-79-3, has been deleted by CAS and is no longer in use.

• Supplier: LC Laboratories
• Product #: S-4490
• Sku #: S-4490_500mg