SBIR CONCEPT AWARD-NANOSPONGE LINKED DCLK1 INHIBITORS FOR THE TARGETED TREATMENT OF CHOLANGIOCARCINOMA

DCLK 1 LLC是一家初创制药公司，专注于开发新型“纳米海绵”， 小分子DCLK 1抑制剂用于治疗胆管癌（CCA），一种罕见的侵袭性 胆管恶性肿瘤，出现在晚期，预后差。CCA的发病率 随着年龄的增长，CCA的5年生存率为13%（中位生存期为7个月）。发生率 CCA正在增加，DCLK 1 LLC估计到2022年美国的发病率将超过10，865。细胞毒性 化疗目前是CCA患者围手术期治疗的标准护理。 DCLK 1 LLC正在与KUMC研究人员合作，研究一种新的CCA治疗策略。 Doublecortin 钙调素样激酶1（DCLK 1）是一种丝氨酸-苏氨酸激酶， 肿瘤学的目标。我们的团队已经证明，DCLK 1表达的敲低和小分子 DCLK 1抑制剂抑制小鼠异种移植肿瘤生长。 DCLK 1 LLC最大限度地提高DCLK 1抑制剂的疗效和安全性的策略是提供这些 使用合理设计的肽， 纳米海绵技术这两种独特的技术结合在一起， 直接对肝脏进行突破性治疗， CCA患者。

DCLK1 LLC is a startup pharmaceutical company focused on developing novel "nano-sponge" linked small molecule DCLK1 inhibitors for treating cholangiocarcinoma (CCA), a rare and aggressive malignancy of the bile ducts that presents at a late stage with poor outcomes. The incidence of CCA increases with age with a 5-Year survival of CCA is 13% (median survival 7 months). Incidence of CCA is increasing and DCLK1 LLC estimates more than 10,865 US incidence in 2022. Cytotoxic chemotherapy is currently the standard of care for CCA patients treated perioperatively. DCLK1 LLC is collaborating with KUMC researchers on a novel treatment strategy for CCA. Doublecortin Calmodulin-like Kinase 1 (DCLK1) is a serine-threonine kinase which represents a novel therapeutic target in oncology. Our team has shown that both knockdown of DCLK1 expression and small molecule DCLK1 inhibitors suppress xenograft tumor growth in mice. DCLK1 LLC's strategy to maximize the efficacy and safety of DCLK1 inhibitors is to deliver these potent molecules to the site of the tumors in the biliary tract using a rationally designed peptide nanosponge technology. Taken together these two unique technologies offer the possibility of administering breakthrough treatment directly to the liver and changing the treatment paradigm for CCA patients.