1,4-DPCA is a potent and selective prolyl-4-hydroxylase inhibitor (IC₅₀=2.4μM) that also suppresses the activity of asparagine hydroxylase factor FIH (IC₅₀=60μM)[1-2]. 1,4-DPCA has potential applications in the treatment of myocardial infarction[3-4].
In vitro, treatment of various breast cancer cell lines (including T4-2, ZR-75-1, MDA-MB-157, and MDA-MB-231) cultured in three-dimensional models with 1,4-DPCA (10–20μM) for 4 days significantly inhibited cell proliferation and reduced invasive phenotypes[5]. Exposure of multiple cell lines (such as H9C2, L929, and cardiomyocytes) to 1,4-DPCA (10–20μM) markedly upregulated HIF-1α protein expression and enhanced cell proliferation [6].
In vivo, a single intramyocardial injection of 1,4-DPCA (delivered via ALG-CHO-TA/DPCA@PDA/MMP-SP/HA-SH hydrogel) at a dose of 100μL (equivalent to 0.4mg/kg) in a rat model of myocardial infarction significantly improved cardiac function and promoted myocardial repair[7]. In a lipopolysaccharide (LPS)-induced septic acute lung injury model in 6–8 week-old C57BL/6J mice, a single tail vein injection of 1,4-DPCA (10mg/kg) acted as a HIF-1α activator, effectively reversing the protective effect of GDF15 overexpression against lung injury[8].
References:
[1] Zhang Y, Strehin I, Bedelbaeva K, et al. Drug-induced regeneration in adult mice. Sci Transl Med. 2015 Jun 3;7(290):290ra92.
[2] Love RJ, Jones KS. Transient inhibition of connective tissue infiltration and collagen deposition into porous poly(lactic-co-glycolic acid) discs. J Biomed Mater Res A. 2013 Dec;101(12):3599-606.
[3] Wang K, Yao SY, Wang Z, et al. A Sequential Dual Functional Supramolecular Hydrogel with Promoted Drug Release to Scavenge ROS and Stabilize HIF-1α for Myocardial Infarction Treatment. Adv Healthc Mater. 2024 Mar;13(6):e2302940.
[4] Zebrowitz E, Aslanukov A, Kajikawa T, et al. Prolyl-hydroxylase inhibitor-induced regeneration of alveolar bone and soft tissue in a mouse model of periodontitis through metabolic reprogramming. Front Dent Med. 2022;3:992722.
[5] Xiong G, Deng L, Zhu J, et al. Prolyl-4-hydroxylase α subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition. BMC Cancer. 2014 Jan 2;14:1.
[6] Deng K, Hua Y, Gao Y, et al. Thermosensitive Hydrogel with Programmable, Self-Regulated HIF-1α Stabilizer Release for Myocardial Infarction Treatment. Adv Sci (Weinh). 2024 Nov;11(43):e2408013.
[7] Wei X, Chen S, Xie T, et al. An MMP-degradable and conductive hydrogel to stabilize HIF-1α for recovering cardiac functions. Theranostics. 2022 Jan 1;12(1):127-142.
[8] Kuang X, Niu Z, Huang Z, et al. GDF15 attenuates sepsis-induced acute lung injury by suppressing the HIF-1α/LDHA pathway. Int Immunopharmacol. 2025 Oct 10;163:115198.
1,4-DPCA一种有效的选择性脯氨酰-4-羟化酶抑制剂（IC50=2.4μM），也可抑制天冬酰胺羟化酶因子FIH活性（IC50=60μM）[1-2]。1,4-DPCA可用心肌梗死治疗[3-4]。
在体外，1,4-DPCA（10–20μM）处理多种乳腺癌细胞系（包括T4-2、ZR-75-1、MDA-MB-157和MDA-MB-231）的三维培养模型4天，显著抑制了细胞增殖并减弱了侵袭性表型[5]。1,4-DPCA（10–20μM）处理多种细胞系（包括H9C2、L929细胞及心肌细胞），显著上调了HIF-1α蛋白的表达水平并促进了细胞增殖[6]。
在体内，1,4-DPCA水凝胶在心肌梗死模型大鼠中进行单次心肌内注射（100μL；0.4mg/kg）。1,4-DPCA显著改善了心脏功能并促进了心肌修复 [7]。1,4-DPCA（10mg/kg）通过尾静脉单次注射，用于处理6-8周龄C57BL/6J小鼠的LPS诱导的脓毒症急性肺损伤模型。1,4-DPCA作为HIF-1α激活剂，显著逆转了GDF15过表达对肺损伤的保护作用[8]。