{"id":1805,"date":"2026-10-13T15:55:20","date_gmt":"2026-10-13T08:25:20","guid":{"rendered":"http:\/\/bioactivecompoundlibrary.com\/?p=1805"},"modified":"2026-10-13T15:55:20","modified_gmt":"2026-10-13T08:25:20","slug":"abmole-mini-lecture%e4%b8%a8pf-05231023-mechanism-and-research-applications-of-a-long-acting-fgf21-analog","status":"publish","type":"post","link":"http:\/\/bioactivecompoundlibrary.com\/index.php\/2026\/10\/13\/abmole-mini-lecture%e4%b8%a8pf-05231023-mechanism-and-research-applications-of-a-long-acting-fgf21-analog\/","title":{"rendered":"AbMole Mini-Lecture\u4e28PF-05231023: Mechanism and Research Applications of a Long-Acting FGF21 Analog"},"content":{"rendered":"\n

PF-05231023 (AbMole, M10048)\u00a0is a long-acting analog of fibroblast growth factor 21 (FGF21). Its molecular structure consists of two modified FGF21 monomers conjugated to an IgG1 \u03ba antibody scaffold. FGF21 is a 19 kDa endocrine hormone that regulates lipid and glucose homeostasis. The N-terminus of FGF21 binds to several fibroblast growth factor receptors (FGFRs), including FGFR1c, FGFR3c, and FGFR4, while its C-terminus primarily binds to the membrane-associated cofactor \u03b2-klotho. Although FGF21 has shown promise in animal models of metabolic diseases, its short half-life of 0.5\u20132 hours limits its application [1]<\/sup>. This is mainly due to its low molecular weight. While fusion protein technology can increase molecular mass, it often compromises the structural integrity of the N- and C-termini, which are critical for the regulatory activity of PF-05231023 [2].<\/sup><\/p>\n\n\n\n

PF-05231023 is generated by site-specifically conjugating two modified FGF21 molecules to a non-targeting IgG1\u03ba antibody scaffold (CVX-2000) via genetic engineering, forming a bivalent FGF21 CovX-Body. Introducing a cysteine residue at position A129 in FGF21 as the conjugation site avoids activity loss associated with N- or C-terminal coupling. This design significantly extends the half-life of FGF21, achieving a 70-fold increase in mice compared to wild-type FGF21 (37 hours after subcutaneous injection). In non-human primates, PF-05231023 has a half-life of 65 hours and a bioavailability of 68% [3]<\/sup>.<\/p>\n\n\n\n

AbMole<\/strong><\/u><\/strong><\/a> provides global researchers with high-purity, high-bioactivity inhibitors, cytokines, human monoclonal antibodies, natural products, fluorescent dyes, peptides, compound libraries, antibiotics, and other research reagents, widely cited in numerous publications and patents worldwide<\/strong>.<\/strong><\/strong><\/p>\n\n\n\n

\"\"<\/a><\/figure>\n\n\n\n

Structure and design mechanism of PF-05231023 [1]<\/sup><\/p>\n\n\n\n

PF-05231023 (AbMole, M10048)<\/strong> significantly inhibits hepatic lipid accumulation in animal models, reduces adipocyte hypertrophy in white adipose tissue, and ameliorates lipid metabolism disorders by downregulating lipid synthesis-related genes in adipose tissue transcriptomes[4]<\/sup>. Moreover, PF-05231023 reduces body weight in animal models by affecting the central nervous system and decreasing food intake. Studies have confirmed that the weight loss induced by PF-05231023 in cynomolgus monkeys and diet-induced obese mice is primarily due to reduced food consumption[5]<\/sup>.<\/p>\n\n\n\n

PF-05231023 is also used in animal models of nonalcoholic steatohepatitis (NASH). In diet-induced NASH mouse models, PF-05231023 significantly reduces body weight, hepatomegaly, plasma transaminase levels, and plasma\/hepatic lipid levels, while also improving liver fibrosis [6]<\/sup>. The mechanism involves inhibition of hepatic lipid droplet accumulation and reduction of adipocyte hypertrophy in white adipose tissue.<\/p>\n\n\n\n

PF-05231023 has important applications in animal models of diabetes and its complications. For example, in insulin-deficient diabetic mice, PF-05231023 activates the AKT-Nrf2 pathway, reduces IL-1\u03b2 expression in photoreceptor cells, protects retinal neuron function, and ameliorates diabetes-induced retinal dysfunction and photoreceptor segment disruption [7]<\/sup>.<\/p>\n\n\n\n

In 2014, two inhibitors from AbMole were used in in vivo studies by the Spanish National Center for Cardiovascular Research (CNIC) and Columbia University, leading to research <\/strong>publications<\/strong><\/u><\/strong><\/a> in Nature and Nature Medicine.<\/strong><\/strong><\/p>\n\n\n\n

Case Study<\/strong><\/strong><\/p>\n\n\n\n

J Adv Res. 2025 Mar;69:477-494.<\/strong><\/strong><\/p>\n\n\n\n

A research team from Wenzhou Medical University investigated the role and mechanism of FGF21 in a mouse model of septic liver injury. They found that FGF21 inhibits septic liver injury via the autophagy\/HIF-1\u03b1 axis. Specifically, FGF21 activates the FGFR receptor, inhibits the mTOR signaling pathway, restores impaired autophagic flux in macrophages during sepsis, promotes p62-mediated autophagic degradation of HIF-1\u03b1, and reduces pro-inflammatory cytokine release and hepatic inflammatory infiltration. PF-05231023 (AbMole, M10048),<\/strong> a long-acting FGF21 analog, was used to inhibit pathological progression and significantly improve survival in septic mouse models. Furthermore, PF-05231023 effectively inhibited the activation of pro-inflammatory macrophages in mice [8]<\/sup>.<\/p>\n\n\n\n

\"\"<\/a><\/figure>\n\n\n\n

PF-05231023 protects mice against septic liver injury [8]<\/sup><\/p>\n\n\n\n

The products described herein are for research use only.<\/p>\n\n\n\n

References and Acknowledgments<\/strong><\/strong><\/p>\n\n\n\n

[1] Jie Huang, Tetsuya Ishino, Gang Chen, et al., Development of a novel long-acting antidiabetic FGF21 mimetic by targeted conjugation to a scaffold antibody, 346(2) (2013) 270-280.<\/p>\n\n\n\n

[2] Junming Yie, Randy Hecht, Jennifer Patel, et al., FGF21 N-and C-termini play different roles in receptor interaction and activation, 583(1) (2009) 19-24.<\/p>\n\n\n\n

[3] J. Huang, T. Ishino, G. Chen, et al., Development of a novel long-acting antidiabetic FGF21 mimetic by targeted conjugation to a scaffold antibody, The Journal of pharmacology and experimental therapeutics 346(2) (2013) 270-80.<\/p>\n\n\n\n

[4] J. Zhao, X. Liu, J. Yue, et al., PF-05231023 reduces lipid deposition in apolipoprotein E-deficient mice by inhibiting the expression of lipid synthesis genes, Frontiers in veterinary science 11 (2024) 1429639.<\/p>\n\n\n\n

[5] W. C. Thompson, Y. Zhou, S. Talukdar, et al., PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates, Journal of pharmacokinetics and pharmacodynamics 43(4) (2016) 411-25.<\/p>\n\n\n\n

[6] M. H. Nielsen, M. P. Gillum, N. Vrang, et al., Hepatoprotective effects of the long-acting fibroblast growth factor 21 analog PF-05231023 in the GAN diet-induced obese and biopsy-confirmed mouse model of nonalcoholic steatohepatitis, American journal of physiology. Gastrointestinal and liver physiology 324(5) (2023) G378-g388.<\/p>\n\n\n\n

[7] Z. Fu, Z. Wang, C. H. Liu, et al., Fibroblast Growth Factor 21 Protects Photoreceptor Function in Type 1 Diabetic Mice, Diabetes 67(5) (2018) 974-985.<\/p>\n\n\n\n

[8] J. Zhu, Z. Jin, J. Wang, et al., FGF21 ameliorates septic liver injury by restraining proinflammatory macrophages activation through the autophagy\/HIF-1\u03b1 axis, Journal of advanced research 69 (2025) 477-494.<\/p>\n","protected":false},"excerpt":{"rendered":"

PF-05231023 (AbMole, M10048)\u00a0is a long-acting analog of fibroblast growth factor 21 (FGF21). Its molecular structure consists of two modified FGF21 monomers conjugated to an IgG1 \u03ba antibody scaffold. FGF21 is a 19 kDa endocrine hormone that regulates lipid and glucose homeostasis. The N-terminus of FGF21 binds to several fibroblast growth factor receptors (FGFRs), including FGFR1c, … <\/p>\n

Continue reading “AbMole Mini-Lecture\u4e28PF-05231023: Mechanism and Research Applications of a Long-Acting FGF21 Analog”<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/1805"}],"collection":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/comments?post=1805"}],"version-history":[{"count":1,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/1805\/revisions"}],"predecessor-version":[{"id":1808,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/posts\/1805\/revisions\/1808"}],"wp:attachment":[{"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/media?parent=1805"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/categories?post=1805"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/bioactivecompoundlibrary.com\/index.php\/wp-json\/wp\/v2\/tags?post=1805"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}