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Wang S, Wang C, Wang X, et al. Antitumor efficacy of CHMFL-KIT-110 solid dispersion in mouse xenograft models of human gastrointestinal stromal tumors. Cancer Chemother Pharmacol. 2021;88(5):795-804doi: 10.1007/s00280-021-04332-z.
Wang, S., Wang, C., Wang, X., Wang, X., Huang, L., Kuai, J., Wei, W., Lu, X., & Yan, S. (2021). Antitumor efficacy of CHMFL-KIT-110 solid dispersion in mouse xenograft models of human gastrointestinal stromal tumors. Cancer chemotherapy and pharmacology, 88(5), 795-804. https://doi.org/10.1007/s00280-021-04332-z
Wang, Shengfu, et al. "Antitumor efficacy of CHMFL-KIT-110 solid dispersion in mouse xenograft models of human gastrointestinal stromal tumors." Cancer chemotherapy and pharmacology vol. 88,5 (2021): 795-804. doi: https://doi.org/10.1007/s00280-021-04332-z
Wang S, Wang C, Wang X, Wang X, Huang L, Kuai J, Wei W, Lu X, Yan S. Antitumor efficacy of CHMFL-KIT-110 solid dispersion in mouse xenograft models of human gastrointestinal stromal tumors. Cancer Chemother Pharmacol. 2021 Nov;88(5):795-804. doi: 10.1007/s00280-021-04332-z. Epub 2021 Jul 26. PMID: 34309733.
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Cancer Chemother Pharmacol. 2021 Nov;88(5):795-804. doi: 10.1007/s00280-021-04332-z. Epub 2021 Jul 26.

Antitumor efficacy of CHMFL-KIT-110 solid dispersion in mouse xenograft models of human gastrointestinal stromal tumors.

Cancer chemotherapy and pharmacology

Shengfu Wang, Chunyan Wang, Xiao Wang, Xiang Wang, Lina Huang, Jiajie Kuai, Wei Wei, Xiaorong Lu, Shangxue Yan

Affiliations

  1. Institute of Clinical Pharmacology, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.
  2. Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education; Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, 81 Meishan Road, Hefei, 230032, China.
  3. Hefei Blooming Drug Safety Evaluation Co., Ltd, 358 Ganquan Road, Hefei, 230031, China.
  4. Anhui Province Key Laboratory of Druggability Evaluation for New Drugs, 358 Ganquan Road, Hefei, 230031, China.
  5. Hefei Blooming Drug Safety Evaluation Co., Ltd, 358 Ganquan Road, Hefei, 230031, China. [email protected].
  6. Anhui Province Key Laboratory of Druggability Evaluation for New Drugs, 358 Ganquan Road, Hefei, 230031, China. [email protected].
  7. Institute of Clinical Pharmacology, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China. [email protected].
  8. Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education; Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, 81 Meishan Road, Hefei, 230032, China. [email protected].

PMID: 34309733 DOI: 10.1007/s00280-021-04332-z

Abstract

PURPOSE: CHMFL-KIT-110, a selective c-KIT kinase inhibitor for gastrointestinal stromal tumors (GISTs), possesses a poorly water-soluble, limiting the further development of the drug. This study was to investigate the antitumor efficacy of CHMFL-KIT-110 and CHMFL-KIT-110 solid dispersion (laboratory code: HYGT-110 SD) in GIST tumor xenograft models and to explore the PK/PD relationship of HYGT-110 SD.

METHODS: Plasma concentrations of HYGT-110 and HYGT-110 SD were determined by LC-MS/MS in KM mice. Antitumor activity was evaluated by measuring tumor volume and weight in c-KIT-dependent GIST xenograft models. PK/PD relationship was assessed by LC-MS/MS and Western Blot in the GIST-T1 xenografted mice.

RESULTS: HYGT-110 exhibited a low oral bioavailability (10.91%) in KM mice. Compared with HYGT-110 treatment, the C

CONCLUSIONS: In comparison with the HPMC formulation, both improved PK and PD characteristics of the solid dispersion formulation of CHMFL-KIT-110 were observed in in vivo animal experiments.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords: Antitumor activity; CHMFL-KIT-110; Gastrointestinal stromal tumors; PK/PD; Solid dispersion

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