OD 36 hydrochloride is a potent inhibitor of RIPK2 kinase with an IC50 value of 5.3nM [1]. OD 36 hydrochloride mimics the interaction between the ATP adenine ring and the hinge region of RIPK2 KD, and utilizes the interaction between the cyclic linker group and the hydrophobic posterior pocket as well as the ribose binding region, thereby enhancing the affinity and selectivity for RIPK2[2]. OD 36 hydrochloride has been widely used in mouse peritonitis models to alleviate inflammation[3].
In vitro, OD 36 hydrochloride treatment (0.5μM) for 21 days significantly inhibited the osteogenic and chondrogenic differentiation induced by activin A in ATDC5 cells expressing mutant R206H ALK2 [4]. The 5.3nM OD 36 hydrochloride treatment for 24 hours significantly inhibited the invasion and metastasis of K7M2 cells promoted by macrophages[5].
In vivo, OD 36 hydrochloride treatment via intraperitoneal injection at a single dose of 6.25mg/kg can reduce the cell infiltration in a muramyl dipeptide (MDP)-induced peritonitis mouse model [6].
References:
[1] Shen S, Lu C, Ling T, et al. Current advances on RIPK2 and its inhibitors in pathological processes: a comprehensive review[J]. Frontiers in Molecular Neuroscience, 2025, 18: 1492807.
[2] Pham A T, Ghilardi A F, Sun L. Recent advances in the development of RIPK2 modulators for the treatment of inflammatory diseases[J]. Frontiers in pharmacology, 2023, 14: 1127722.
[3] You J, Wang Y, Chen H, et al. RIPK2: a promising target for cancer treatment[J]. Frontiers in pharmacology, 2023, 14: 1192970.
[4] Sánchez Duffhues G, Williams E, Benderitter P, et al. Development of Macrocycle Kinase Inhibitors for ALK2 Using Fibrodysplasia Ossificans Progressiva Derived Endothelial Cells[J]. Journal of Bone and Mineral Research Plus, 2019, 3(11): e10230.
[5] Maloney C, Kallis M P, Edelman M, et al. Gefitinib inhibits invasion and metastasis of osteosarcoma via inhibition of macrophage receptor interacting serine-threonine kinase 2[J]. Molecular cancer therapeutics, 2020, 19(6): 1340-1350.
[6] Tigno-Aranjuez J T, Benderitter P, Rombouts F, et al. In vivo inhibition of RIPK2 kinase alleviates inflammatory disease[J]. Journal of Biological Chemistry, 2014, 289(43): 29651-29664.
OD 36 hydrochloride是一种强效的RIPK2激酶抑制剂，IC50值为5.3nM[1]。OD 36 hydrochloride模拟ATP腺嘌呤环与RIPK2 KD铰链区之间的相互作用，并利用环状连接基团与疏水后口袋以及核糖结合区之间的相互作用，从而增强对RIPK2的亲和力和选择性[2]。OD 36 hydrochloride已被广泛用于小鼠腹膜炎模型以减轻炎症[3]。
在体外，0.5μM的OD 36 hydrochloride处理表达突变型R206H ALK2的ATDC5细胞21天，显著抑制了activin A诱导的成骨和成软骨分化[4]。5.3nM的OD 36 hydrochloride 处理24小时，显著抑制了巨噬细胞促进的K7M2细胞侵袭和转移[5]。
在体内，单次腹腔注射6.25mg/kg剂量的OD 36 hydrochloride，可减少muramyl dipeptide (MDP)诱导的腹膜炎小鼠模型中的细胞浸润[6]。