CaMKII-IN-1 is a potent and highly selective CaMKII inhibitor with an IC50 value of 63nM [1]. CaMKII-IN-1 can inhibit the phosphorylation of CaMKII, p38 and Jnk, reduce the basal expression levels of MMP2, MMP9 and MCP1, as well as the expression level of Ang II, and prevent cell apoptosis by inhibiting the upregulation of Bax and cleaved caspase-3[2]. CAMKII-IN-1 has been widely used to inhibit the biosynthesis of Juvenile hormone (JH) and regulate the interaction between CREB and CBP[3].
In vitro, CAMKII-IN-1 treatment (40nM) for 48 hours reversed the elevated levels of p-CaMKII and p-Akt proteins in deES-2 cells with overexpressed CACNA1H, restoring the protein levels of LC3-II/LC3-I and Beclin1[4]. Treatment with 100nM CAMKII-IN-1 for 48 hours prevented the upregulation of Il17d expression in MC38 cells induced by WNT11, and reversed the increase in NF-κB p65 nuclear translocation induced by WNT11[5]. The 1-hour pre-treatment with CAMKII-IN-1 (100nM) significantly inhibited the upregulation of TGFα in BV2 cells after glibenclamide treatment[6]. The treatment with CAMKII-IN-1 (30nM) for 72 hours significantly promoted the proliferation of IEC-6 cells after serum deprivation[7].
In vivo, CAMKII-IN-1 treatment via microinjection into the nucleus accumbens shell (NAcsh) at a single dose of 63nM (1μl per side) rescued the stress sensitivity induced by LV-shPRCP in mice subjected to sub-threshold social defeat stress (SSDS), including an increase in social interaction rate and a reduction in inactivity time[8].
References:
[1] Asano S, Komiya M, Koike N, et al. 5, 6, 7, 8-Tetrahydropyrido [4, 3-d] pyrimidines as novel class of potent and highly selective CaMKII inhibitors[J]. Bioorganic & medicinal chemistry letters, 2010, 20(22): 6696-6698.
[2] Xu C, Xu J, Zou C, et al. Chronic Intermittent Hypoxia Regulates CaMKII‐Dependent MAPK Signaling to Promote the Initiation of Abdominal Aortic Aneurysm[J]. Oxidative Medicine and Cellular Longevity, 2021, 2021(1): 2502324.
[3] Zhu S, Liu F, Chen X, et al. Inter-organelle communication dynamically orchestrates juvenile hormone biosynthesis and female reproduction[J]. National Science Review, 2025, 12(3): nwaf022.
[4] Shi H, Zheng L, Jiang X, et al. CACNA1H restrains chemotherapy resistance in ovarian clear cell carcinoma cells by repressing autophagy[J]. Molecular Genetics and Genomics, 2024, 299(1): 77.
[5] Jiang W, Guan B, Sun H, et al. WNT11 promotes immune evasion and resistance to Anti-PD-1 therapy in liver metastasis[J]. Nature Communications, 2025, 16(1): 1429.
[6] He Y, Peng Y, Chang Y, et al. Blocking SUR1-TRPM4 reduces neuronal loss in peri-infarct area via stimulating TGFα released by microglia[J]. 2022.
[7] Lei X, Xu Z, Liu X, et al. Melatonin Influences Bmi1+ Intestinal Stem Cell Fate Through Metabolic Regulation After Irradiation[J]. Journal of Pineal Research, 2026, 78(1): e70110.
[8] Deng Q, Zhang S, Yang P, et al. α-MSH-catabolic enzyme prolylcarboxypeptidase in nucleus accumbens shell ameliorates stress susceptibility in mice through regulating synaptic plasticity[J]. Acta Pharmacologica Sinica, 2023, 44(8): 1576-1588.
CaMKII-IN-1是一种强效且高度选择性的CaMKII抑制剂，IC50值为63nM[1]。CaMKII-IN-1可抑制 CaMKII、p38和Jnk的磷酸化，降低MMP2、MMP9和MCP1的基础表达水平以及Ang II的表达水平，并通过抑制Bax和cleaved caspase-3的上调来防止细胞凋亡[2]。CAMKII-IN-1已被广泛用于抑制Juvenile hormone (JH)的生物合成，并调节CREB与CBP之间的相互作用[3]。
在体外，40nM的CAMKII-IN-1处理过表达CACNA1H的deES-2细胞48小时，逆转了p-CaMKII和p-Akt蛋白水平的升高，恢复了LC3-II/LC3-I和Beclin1的蛋白水平[4]。100nM的CAMKII-IN-1处理MC38 细胞48小时，阻止了WNT11诱导的Il17d表达上调，并逆转了WNT11诱导的NF-κB p65核转位增加[5]。100nM的CAMKII-IN-1预处理1小时，显著抑制了glibenclamide处理后BV2细胞中TGFα的上调[6]。30nM的CAMKII-IN-1处理IEC-6细胞72小时，显著促进了血清剥夺后的细胞增殖[7]。
在体内，将单剂量63nM（每侧1μl）的CAMKII-IN-1显微注射到伏隔核壳(NAcsh)中，挽救了LV-shPRCP诱导的亚阈值社交失败应激（SSDS）小鼠的应激敏感性，表现为社会互动率增加和不活动时间减少[8]。