生物活性

• 靶点	Bcr-Abl IC50:34nM

• 描述The BCR-ABL1 oncogene is a fusion protein that results from transposition of a segment of the c-ABL1 gene from chromosome 9q34 onto the BCR gene on chromosome 22q11. It encodes a cytoplasmic protein tyrosine kinase with elevated and dysregulated enzymatic activity that plays a vital role in the pathogenesis and progression of chronic myeloid leukemia (CML)^[5]. Radotinib, a novel and selective BCR-ABL1 tyrosine kinase inhibitor with IC₅₀ of 34 nM, is used for the treatment of CML^[6]. Cell viability of K562 (a representative CML cell line) cells was significantly reduced even at the lowest concentration of radotinib (12.5 μM), indicating that radotinib kills K562 cells directly. The purified NK cells were incubated with various doses (0, 12.5, 25, 50, 100, and 200 μM) of radotinib. NK cell cytotoxicity was markedly upregulated upon radotinib treatment indicating radotinib could be used as an effective and strong therapeutic to treat solid tumors via upregulation of NK cell cytotoxicity^[7].

• 动物研究
  剂量	Mice: 10 mg/kg, 20 mg/kg[3] (i.p.); 3 mg/kg - 30 mg/kg[4] (p.o.)
  给药途径	i.p., p.o.
  动物药代数据	Animal Mice[4] Dose 30 mg/kg Administration p.o. Cmax 10082.9 ng/ml AUCt 87081.4 ng·h/ml

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02421926	-	-	Withdrawn	May 2023	Korea, Republic of ... more >> Seoul National University Bundang Hospital Seongnam, Gyong-gi Province, Korea, Republic of Korea University Ansan Hospital Ansan, Korea, Republic of Busan National University Hospital Busan, Korea, Republic of Haeundae Paik Hospital Busan, Korea, Republic of Chungnam National University Hospital Daejeon, Korea, Republic of Gachon University Gil Hospital Incheon, Korea, Republic of Asan Medical Center Seoul, Korea, Republic of Korea University Anam Hospital Seoul, Korea, Republic of Korea University Guro Hospital Seoul, Korea, Republic of Seoul National University Hospital Seoul, Korea, Republic of Soonchyunhyang University Hospital Seoul, Korea, Republic of Ajou University Hospital Suwon, Korea, Republic of Collapse <<
  NCT01602952	Leukemia Leuk... more >>emia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Philadelphia Chromosome Hematologic Diseases Collapse <<	Phase 1 Phase 2	Completed	-	India ... more >> Local institution Mumbai, Maharashtra, India, 741-234 Local institution Mumbai, Mazagaon, India, 512-364 Korea, Republic of Local institution Daegu, Buk-gu, Korea, Republic of, 511-230 Local institution Jeonju, Deokjin-gu, Korea, Republic of, 212-789 Local institution Ulsan, Dong-gu, Korea, Republic of, 411-978 Local institution Anyang-si, Dongan-gu, Korea, Republic of, 751-231 Local institution Hwasun, Hwasun-eup, Korea, Republic of, 322-511 Local institution Seoul, Jongro-ku, Korea, Republic of, 231-855 Local institution Busan, Seo-gu, Korea, Republic of, 400-321 Seoul St. Mary's hospital Seoul, Seocho-gu, Korea, Republic of Local institution Suwon, Yeongtong-gu, Korea, Republic of, 781-512 Thailand Local institution Bangkok, Phyathai, Thailand, 215-714 Collapse <<
  NCT03722420	Chronic Myeloid Leukemia, Chro... more >>nic Phase Collapse <<	Phase 3	Not yet recruiting	December 31, 2023	-

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• 参考文献

• [1] Heo SK, Noh EK, et al. Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells. PLoS One. 2015 Jun 12;10(6):e0129853.

  [2] Kim SH, Menon H, et al. Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitors. Haematologica. 2014 Jul;99(7):1191-6.

  [3] Heo SK, Noh EK, et al. Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression. Tumour Biol. 2019 May;41(5):1010428319848612.

  [4] Lee S, Kim S, et al. The c-Abl inhibitor, Radotinib HCl, is neuroprotective in a preclinical Parkinson's disease mouse model. Hum Mol Genet. 2018 Jul 1;27(13):2344-2356.

  [5] Tsubaki M, Takeda T, Kino T, Sakai K, Itoh T, Imano M, Nakayama T, Nishio K, Satou T, Nishida S. Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance in chronic myeloid leukemia cells. Oncotarget. 2017 Jun 13;8(24):38717-38730. doi: 10.18632/oncotarget.16314. PMID: 28418880; PMCID: PMC5503566.

  [6] Kim SH, Menon H, Jootar S, Saikia T, Kwak JY, Sohn SK, Park JS, Jeong SH, Kim HJ, Kim YK, Oh SJ, Kim H, Zang DY, Chung JS, Shin HJ, Do YR, Kim JA, Kim DY, Choi CW, Park S, Park HL, Lee GY, Cho DJ, Shin JS, Kim DW. Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitors. Haematologica. 2014 Jul;99(7):1191-6. doi: 10.3324/haematol.2013.096776. Epub 2014 Apr 4. PMID: 24705186; PMCID: PMC4077080.

  [7] Kim KE, Park S, Cheon S, Kim DY, Cho DJ, Park JM, Hur DY, Park HJ, Cho D. Novel Application of Radotinib for the Treatment of Solid Tumors via Natural Killer Cell Activation. J Immunol Res. 2018 Dec 31;2018:9580561. doi: 10.1155/2018/9580561. PMID: 30687767; PMCID: PMC6330826.

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