Klotho, a key modulator of aging process and age-related diseases
The klotho was originally identified as a putative age-suppressing gene in mice that extends life span when overexpressed. Klotho is involved in signaling pathways and in regulation of a proper cell metabolism for example acting as a coreceptor for fibroblast growth factor (FGF) and an inhibition of insulin/insulin-like growth factor-1. Furthermore, clinical evidence showed association between Klotho and age-related diseases such as cardiovascular disease and tumor.
Klotho is a single-pass transmembrane protein composing of a large extracellular domain (~130 kD), a transmembrane domain, and a noticeably short intracellular domain (10 amino acids). Three Klotho-related genes were identified based on sequence similarity and designated as α-Klotho, β-Klotho and γ-Klotho (also known as KLPH or LCTL). α-Klotho is expressed primarily in the kidney, β-Klotho is expressed in various tissues, most notably in the liver and white adipose tissue, γ-Klotho is expressed in eyes. All three types of Klotho proteins can form complexes with FGF receptors and these Klotho-FGFR complexes function as high-affinity receptor for endocrine FGFs (FGFs showed function as hormones, including FGF19, FGF21, and FGF23). FGF23 requires α-Klotho, FGF19 requires β-Klotho or γ-Klotho, whereas FGF21 requires β-Klotho.
FGF21 is secreted from the liver upon fasting and acts on white adipose tissue to induce lipolysis and the metabolic adaptation to fasting. As exogenously administered FGF21 acts directly on adipose tissue to reduce blood glucose levels and increase hepatic, and possibly peripheral, insulin sensitivity, decrease body weight and decrease serum lipids, FGF21 became a promising therapeutic candidate for the treatment of type 2 diabetes. However, due to the proteolytic cleavage of recombinant human FGF21 in preclinical species, people took sights to its receptor FGFR1c and co-receptor β-klotho. NGM313 (MK-3655) is a proprietary, monoclonal agonistic antibody selectively activating FGFR1c/KLB, the drug is being studied to treat nonalcoholic steatohepatitis (NASH) and type 2 diabetes by MSD and NGM Biopharmaceuticals.
Based on our featured SAMSTM platform, Kactus has developed full-length β-klotho protein. The bioactivity has been tested using multiple anti-Klotho antibodies (with different epitopes) and verified by our customers.
Full-length β-klotho without sequence modification;
Low-endotoxin (<1EU per μg by the LAL method) and high-purity (>95%);
High degree of batch-to-batch consistency.
Fig. 1 Bioactivity assay by ELISA using different antibodies.
Fig. 2 Human Klotho full length, His Tag captured on CM5 Chip via anti-His antibody can bind Human FGF21, mFc Tag with an affinity constant of 0.54nM as determined in SPR assay (Biacore T200).