Diprovocim-1 is a TLR1/TLR2 agonist, with EC50 values of 0.11nM and 1.3nM in THP-1 cells and mouse macrophages, respectively[1]. Diprovocim-1 induces the formation of TLR2/TLR1 heterodimers as well as TLR2 homodimers in vitro[2]. Diprovocim-1 has been widely used as an adjuvant in combination with anti-PD-L1 therapy to eliminate melanoma in mice[3].
In vitro, Diprovocim-1 treatment (10nM) for 4h significantly enhanced the levels of tumor necrosis factor (TNF) in mouse peritoneal macrophages [4].
In vivo, a single intraperitoneal injection of Diprovocim-1 (10mg/kg) and ovalbumin (OVA) (5mg/kg) for 14 days significantly increased the levels of OVA-specific circulating antibodies of different subtypes in serum of C57BL/6J mice[5]. Diprovocim-1 (10mg/kg) administered intraperitoneally to C57BL/6 mice at 18h and 2h before 12Gy total body irradiation (TBI) significantly ameliorated radiation-induced intestinal injury, reduced leukocyte loss, and alleviated body weight loss[6].
References:
[1] Morin M D, Wang Y, Jones B T, et al. Diprovocims: a new and exceptionally potent class of toll-like receptor agonists[J]. Journal of the American Chemical Society, 2018, 140(43): 14440-14454.
[2] Su L, Wang Y, Wang J, et al. Structural basis of TLR2/TLR1 activation by the synthetic agonist diprovocim[J]. Journal of medicinal chemistry, 2019, 62(6): 2938-2949.
[3] Hu H G, Li Y M. Emerging adjuvants for cancer immunotherapy[J]. Frontiers in Chemistry, 2020, 8: 601.
[4] Wang Y, Su L, Morin M D, et al. Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti–PD-L1 to eliminate melanoma in mice[J]. Proceedings of the National Academy of Sciences, 2018, 115(37): E8698-E8706.
[5] Yang M H, Russell J L, Mifune Y, et al. Next-generation diprovocims with potent human and murine TLR1/TLR2 agonist activity that activate the innate and adaptive immune response[J]. Journal of medicinal chemistry, 2022, 65(13): 9230-9252.
[6] Fang D, Zhao H, Pei L, et al. Diprovocim protects against the radiation-induced damage via the TLR2 signaling pathway[J]. Molecular Medicine, 2025, 31(1): 139.
Diprovocim-1是一种TLR1/TLR2激动剂，在THP-1细胞和小鼠巨噬细胞中的EC50值分别为0.11nM和1.3nM[1]。Diprovocim-1可在体外诱导TLR2/TLR1异源二聚体及TLR2同源二聚体的形成[2]。Diprovocim-1已广泛作为佐剂与抗PD-L1疗法联用，在小鼠模型中实现黑色素瘤的清除[3]。
在体外，使用10nM的Diprovocim-1处理小鼠腹腔巨噬细胞4小时，能显著提升肿瘤坏死因子(TNF)水平[4]。
在体内，单次腹腔注射Diprovocim-1(10mg/kg)与卵清蛋白(OVA)(5mg/kg)14天后，可显著提高C57BL/6J小鼠血清中OVA特异性循环抗体各亚型的水平[5]。在全身辐射(TBI)前18小时和2小时对C57BL/6小鼠腹腔注射Diprovocim-1(10mg/kg)，能显著改善辐射诱导的肠道损伤，减少白细胞损失，并缓解体重下降[6]。