ABR-238901 is a newly developed blocker for S100A8/A9, which effectively inhibits the interaction between S100A8/A9 and the receptor for advanced glycation endproducts (RAGE) as well as toll-like receptor 4 (TLR4) [1-2].
ABR-238901(30 mg/kg；i.p) ameliorates septic cardiomyopathy in mice [3]. ABR-238901, administered at a dose of 10 mg/kg intraperitoneally, reduces neutrophil extracellular trap (NET) formation in abdominal sepsis by inhibiting S100A9[4]. In abdominal sepsis, ABR-238901 at doses of 30 mg/kg administered intraperitoneally reduced lung levels of MPO (a marker of neutrophil activation) by 74% [5]. In mice with multiple myeloma (MM), treatment with ABR-238901 at a dose of 30 mg/kg given orally daily for 5 days reduces angiogenesis in vivo[6]. Administering ABR-238901 at a dose of 30 mg/kg intraperitoneally for a short duration shifts the balance between inflammation and repair towards a reparatory environment in the ischemic myocardium [7].
References:
[1]. Zhu H, He M, et,al. Low-intensity pulsed ultrasound alleviates doxorubicin-induced cardiotoxicity via inhibition of S100a8/a9-mediated cardiac recruitment of neutrophils. Bioeng Transl Med. 2023 Jul 7;8(6):e10570. doi: 10.1002/btm2.10570. PMID: 38023700; PMCID: PMC10658545.
[2]. Mareş RG, Sabău AH, et,al. S100A8∕A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction. Rom J Morphol Embryol. 2023 Apr-Jun;64(2):151-158. doi: 10.47162/RJME.64.2.04. PMID: 37518871; PMCID: PMC10520380.
[3]. Jakobsson G, Papareddy P, et,al. Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction. Crit Care. 2023 Sep 29;27(1):374. doi: 10.1186/s13054-023-04652-x. PMID: 37773186; PMCID: PMC10540409.
[4]. Du F, Ding Z, et,al. S100A9 induces reactive oxygen species-dependent formation of neutrophil extracellular traps in abdominal sepsis. Exp Cell Res. 2022 Dec 15;421(2):113405. doi: 10.1016/j.yexcr.2022.113405. Epub 2022 Oct 31. PMID: 36328195.
[5]. Ding Z, Du F, et,al. Targeting S100A9 Reduces Neutrophil Recruitment, Inflammation and Lung Damage in Abdominal Sepsis. Int J Mol Sci. 2021 Nov 29;22(23):12923. doi: 10.3390/ijms222312923. PMID: 34884728; PMCID: PMC8658007.
[6]. De Veirman K, De Beule N, et,al. Extracellular S100A9 Protein in Bone Marrow Supports Multiple Myeloma Survival by Stimulating Angiogenesis and Cytokine Secretion. Cancer Immunol Res. 2017 Oct;5(10):839-846. doi: 10.1158/2326-6066.CIR-17-0192. Epub 2017 Sep 13. PMID: 28903971.
[7]. Marinković G, Koenis DS, et,al. S100A9 Links Inflammation and Repair in Myocardial Infarction. Circ Res. 2020 Aug 14;127(5):664-676. doi: 10.1161/CIRCRESAHA.120.315865. Epub 2020 May 21. PMID: 32434457.
ABR-238901是S100A8/A9阻断剂，有效抑制了S100A8/A9与高级糖基化终产物受体(RAGE)以及Toll样受体4(TLR4)之间的相互作用[1-2]。
ABR-238901(30 mg/kg；i.p)改善了小鼠的感染性心肌病[3]。ABR-238901以每公斤10毫克的剂量腹腔注射，通过抑制S100A9减少了腹部感染的中性粒细胞外网（NET）的形成[4]。在腹部感染中，ABR-238901以30 mg/kg剂量腹腔注射，将肺部MPO（中性粒细胞活化标志物）水平降低了74%[5]。在多发性骨髓瘤（MM）小鼠中，每日口服30 mg/kg 的ABR-238901治疗5天可降低体内血管生成[6]。腹腔注射30 mg/kg的ABR-238901，短期内改变了缺血性心肌组织中炎症修复平衡，使其向修复环境转变[7]。