TASIN-1 hydrochloride 

TASIN-1 hydrochloride is a selective inhibitor of truncated APC^TR (adenomatous polyposis coli gene) that exerts cytotoxic effects by inhibiting cholesterol biosynthesis. TASIN-1 hydrochloride specifically targets colorectal cancer (CRC) cells carrying APC truncated mutations, while having no significant toxicity to wild-type APC cells. TASIN-1 hydrochloride exerts cytotoxic effects by targeting Emopamil binding protein (EBP) to inhibit cholesterol biosynthesis, triggering endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) generation, and JNK-mediated apoptosis, and inhibiting Akt survival signaling. TASIN-1 hydrochloride can be used to prevent and intervene in APC mutant colorectal cancer^[1][2][3].

TASIN-1 hydrochloride 对 DLD1 细胞中截短型腺瘤性息肉病 coli (APC^TR) 具有选择性抑制，IC₅₀=70 nM^[1]。
TASIN-1 hydrochloride (70 nM；72 h) 显著抑制人结肠癌细胞 DLD1 (APC^TR) 增殖，IC₅₀ 为 70 nM，对 HCT116 (APC^WT) 细胞 IC₅₀ >50 μM，显示高度选择性^[1]。
TASIN-1 hydrochloride (2.5 μM；7 d) 抑制 DLD1 细胞软琼脂集落形成，而对 HCT116 无显著影响^[1]。
TASIN-1 hydrochloride (2.5 μM；2-48 h) 减少 DLD1 细胞胆固醇合成速率，降低内源性胆固醇水平，对 HCT116 无作用^[1]。
TASIN-1 hydrochloride (2.5 μM；24 h) 在 DLD1 细胞中诱导内质网应激标志物 CHOP 表达和 JNK 磷酸化，激活 caspase 3/7 活性，而在 HCT116 细胞中无明显变化^[2]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

TASIN-1 (40 mg/kg；腹腔注射；每日 2 次；18 天) hydrochloride 显著抑制裸鼠 DLD1/HT29 (APC^TR) 皮下异种移植模型的肿瘤生长，诱导肿瘤细胞凋亡，但对 HCT116 (APC^WT) 肿瘤无抑制作用^[1]。
TASIN-1 (20，40 mg/kg；腹腔注射；每周 2 次；90 或 100 天) hydrochloride 在 CPC;Apc 小鼠的遗传性结直肠癌模型中，减少结肠息肉数量和大小，抑制肿瘤进展，且无明显肝肾功能损伤或体重下降^[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

388.95

C₁₈H₂₉ClN₂O₃S

1678515-13-3

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Zhang L, et al. Selective targeting of mutant adenomatous polyposis coli (APC) in colorectal cancer. Sci Transl Med. 2016 Oct 19;8(361):361ra140.  [Content Brief]

  [2]. Zhang L, et al. Cholesterol Depletion by TASIN-1 Induces Apoptotic Cell Death through the ER Stress/ROS/JNK Signaling in Colon Cancer Cells. Mol Cancer Ther. 2018 May;17(5):943-951.  [Content Brief]

  [3]. Wang W, et al. Design and Synthesis of TASIN Analogues Specifically Targeting Colorectal Cancer Cell Lines with Mutant Adenomatous Polyposis Coli (APC). J Med Chem. 2019 May 23;62(10):5217-5241.  [Content Brief]