K-Ras Isoform A (G12D mutant; human, recombinant)

K-Ras is a small GTPase and member of the RAS family of GTPases with roles in apoptosis, as well as cell proliferation, survival, and migration.^1,2 K-Ras is composed of a guanine nucleotide-binding domain containing an active site, an effector binding domain, and an isoform-specific C-terminal hypervariable region (HVR) that differs between K-Ras isoforms A and B due to alternative splicing.^1,3,4 The active site cycles between GDP-bound inactive and GTP-bound active states and is regulated by its associations with GTPase-activating proteins (GAPs) or guanine nucleotide exchange factors (GEFs).^3,5 K-Ras is ubiquitously expressed and is tethered to the intracellular side of cell membranes via farnesyl and palmitoyl lipidation and to negatively charged or neutral regions of the membrane via a single polybasic region in the HVR.^1,6,4 K-Ras^G12D, which contains a glycine-to-aspartic acid substitution at position 12, is constitutively active and associated with pancreatic, colon, and lung cancers.⁷ Inhibition of K-Ras^G12D with the inhibitory peptide KS-58 reduces tumor volume in a PANC-1 pancreatic cancer mouse xenograft model.⁸ Tumor levels of K-Ras^G12D are increased in patients with lung adenocarcinoma who had never smoked.⁹ Cayman's K-Ras Isoform A (G12D mutant; human, recombinant) protein consists of 185 amino acids and has a calculated molecular weight of 23 kDa.

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8. Sakamoto, K., Masutani, T., and Hirokawa, T. Generation of KS-58 as the first K-Ras(G12D)-inhibitory peptide presenting anti-cancer activity in vivo. Sci. Rep. 10, 21671 (2020).

9. Dogan, S., Shen, R., Ang, D.C., et al. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: Higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin. Cancer Res. 18(22), 6169-6177 (2012).