Month: August 2019

BAY-293 is a Selective KRas-SOS1 Inhibitor for RAS-Driven Tumors Treatment

Members of the RAS family of GTPases (which comprises KRAS, NRAS, and HRAS) are major oncogenes. Especially, mutations in the RAS genes are major oncogenes with a high occurrence rate in human cancers. RAS-RAF-MEK-ERK and RAS-PI3K-PDK1-AKT pathways are essential to cell survival and proliferation. SOS1 is also the guanine...

ARV-825 is a PROTAC Degrader of BRD4 with Profound Anti-Leukemic Effect

BRD4 (Bromodomain-containing protein 4) belongs to the BET family, which also contains BRD2, BRD3, and BRDT. BRD4 has two bromodomains to recognize acetylated lysine residues. They are BD1 and BD2. It also contains an extended C-terminal domain. The latter interacts with P-TEFb and RNA polymerase II to promote gene...

RG7112 is the First Clinical and Orally Active MDM2-p53 Inhibitor

Yesterday, I introduced AMG 232 as a potent, selective and orally available inhibitor of p53-MDM2 interaction. Additionally, we have known the significance of MDM2-p53 interaction in cancer development. Today, I’d like to introduce another orally available MDM-2-p53 intreraction inhibitor, RG7112. RG7112 binds selectively to the p53 pocket on the...

AMG 232 is an Orally Active and Best-in-Class MDM2-p53 Inhibitor

The p53 tumor suppressor induces cell growth arrest and apoptosis in response to DNA damage or stress. And inactivation of the p53 pathway plays an indispensable role in tumor survival. Approximately p53 mutations resulting in loss of its function account for 50% human cancers. And the wild-type p53, present...

AAPK-25 is a Selective and Dual Aurora/PLK Inhibitor

The occurrence of many cancers is due to mismatch of chromosome. It leads to the formation of aneuploidy and incomplete genes, and hence triggering imbalance of cell cycles or divisions in the mitotic phase. Aurora and Polo-like kinases (PLKs) control the G2/M phase in cell mitosis. They are crucial...

CP-10 is a Specific PROTAC Degrader of CDK6

CDK6 plays a significant role in cell cycle entrance. However, overexpression of CDK6 correlates to CDK4/6 inhibitor resistance in breast cancer cell lines and patient samples. Moreover, point mutation of CDK6 could possibly result in attenuation of drug binding affinity or hyperactivation of CDK6. Thus, there is an urgent...