Ceapin-A7 is a selective blocker of endoplasmic reticulum stress ATF6α signaling (IC50= 0.59μM)[1]. Ceapin-A7 can inhibit Th17 cell differentiation[2]. Ceapin-A7 protects cells from Zika virus infection and also has the function of increasing the radiosensitivity of cancer cells[3-4].
In vitro, pretreatment of ccRCC cells (ACHN and 786-O) with Ceapin-A7 (20μM) for 24 hours reduced the protein expression of PINK1 and BNIP3, and promoted cell proliferation and migration[5]. Pretreatment of bovine pulmonary artery endothelial cells (BPAEC) with Ceapin-A7 (15μM) for 24 hours, followed by stimulation with LPS (1μg/ml) for 2 hours, significantly enhanced the phosphorylation activation of STAT3, JAK2, and JNK, while exacerbating the inhibition of cell proliferation[6].
In vivo, Ceapin-A7 (10mg/kg) was administered via intraperitoneal injection three times per week to DBA/1J mice with collagen-induced arthritis (CIA), from day 22 to day 45, Ceapin-A7 significantly alleviated arthritis severity and joint bone erosion[7]. Ceapin-A7 (1μM) was administered via drinking water to curdlan-induced SKG mice, from week 1 until week 12. Ceapin-A7 significantly alleviated spinal ankylosis and osteophyte formation[8].
References:
[1] Fakir S, Sigdel M, Sarker MMR, et al. Ceapin-A7 suppresses the protective effects of Octreotide in human and bovine lung endothelial cells. Cell Stress Chaperones. 2025 Feb;30(1):1-8.
[2] Kubra KT, Akhter MS, Saini Y, et al. Activating transcription factor 6 protects against endothelial barrier dysfunction. Cell Signal. 2022 Nov;99:110432.
[3] Kern J, Schilling D, Schneeweis C, et al. Identification of the unfolded protein response pathway as target for radiosensitization in pancreatic cancer. Radiother Oncol. 2024 Feb;191:110059.
[4] Mufrrih M, Chen B, Chan SW. Zika Virus Induces an Atypical Tripartite Unfolded Protein Response with Sustained Sensor and Transient Effector Activation and a Blunted BiP Response. mSphere. 2021 Jun 30;6(3):e0036121.
[5] Yan M, Wang J, Wang H, et al. Knockdown of NR3C1 inhibits the proliferation and migration of clear cell renal cell carcinoma through activating endoplasmic reticulum stress-mitophagy. J Transl Med. 2023 Oct 8;21(1):701.
[6] Kubra KT, Barabutis N. Ceapin-A7 potentiates lipopolysaccharide-induced endothelial injury. J Biochem Mol Toxicol. 2023 Nov;37(11):e23460.
[7] Ge L, Wang T, Shi D, et al. ATF6α contributes to rheumatoid arthritis by inducing inflammatory cytokine production and apoptosis resistance. Front Immunol. 2022 Oct 10;13:965708.
[8] Ma M, Li H, Wang P, et al. ATF6 aggravates angiogenesis-osteogenesis coupling during ankylosing spondylitis by mediating FGF2 expression in chondrocytes. iScience. 2021 Jun 28;24(7):102791.