Pharmews

  近期正大天晴药业公开了HPK1抑制剂的专利（WO2023160577），“本申请涉及含有吡咯啉酮的稠合双环化合物、其制备方法、含有该化合物的药物组合物、以及其在治疗疾病(例如癌症)中的用途”。 该专利具体涉及式(II)所示化合物、其立体异构体或其药学上可接受的盐，对该专利涉及的化合物进行HPK1体外激酶抑制活性检测，IC50值在个位数范围，对Jurkat细胞p-SLP76磷酸化抑制活性检测结果显示，IC50大部分＜50nM。其中部分实施例结构如下图： 此前中国生物制药曾对Treadwell进行战略投资，就其肿瘤药HPK1抑制剂达成合作意向，获得该产品的中国开发选择权，目前该产品尚处于临床1/2期临床阶段（启动于2020年）： In the efficacy evaluable population (N=31) , 2 patients achieved partial response as best response. Both of responses were in Head and Neck Squamous Cell Carcinoma (HNSCC) patients previously treated with pembrolizumab. One patient was treated as a monotherapy (400 mg) and the other treated in combination (60 mg + pembrolizumab) with 36% and 81% reduction in target lesions, respectively. Nine patients had best response as stable disease and stayed on study for at least 4 cycles. The most common treatment emergent toxicities of any grade, which occurred in greater than 10% of patients, were diarrhea (61%), fatigue (39%), nausea (33%), decreased appetite (30%), vomiting (2