OBP-801 - CAS 328548-11-4
Catalog number:
328548-11-4
Category:
Inhibitor
Not Intended for Therapeutic Use. For research use only.
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Description:
OBP-801, also known YM753 and spiruchostatin A, is a novel cyclic-peptide-based HDAC inhibitor. YM753 is a bacteria-derived natural product containing a disulfide bond. It potently inhibited HDAC enzyme with an IC50 of 2.0 nM in the presence of dithiothreitol. YM753 was rapidly converted to a reduced form in tumor cells, and then induced accumulation of acetylated histones, followed by p21WAF1/Cip1 expression, tumor cell growth inhibition and tumor-selective cell death. In an in vitro washout study, YM753 showed prolonged accumulation of acetylated histones in WiDr human colon carcinoma cells. In vivo YM753 dosing of mice harboring WiDr colon tumor xenografts significantly inhibited the tumor growth via sustained accumulation of acetylated histones in the tumor tissue. In a pharmacokinetic study, YM753 rapidly disappeared from the plasma, but its reduced form remained in the tumor tissue. Moreover, the accumulation of acetylated histones induced by YM753 was tumor tissue selective compared to several normal tissues. YM753 has attractive pharmacodynamic and pharmacokinetic properties giving it potential as an antitumor agent.
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Purity:
>98%
Appearance:
white solid powder
Synonyms:
OBP 801; OBP801; YM-753; YM753; YM 753; Spiruchostatin A
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Current Developer:
Oncolys BioPharma Inc. / Astellas Pharma Inc.
1.The novel HDAC inhibitor OBP-801/YM753 enhances the effects of 5-fluorouracil with radiation on esophageal squamous carcinoma cells.
Furutani A1, Sowa Y, Fujiwara H, Otsuji E, Sakai T. Oncol Res. 2014;21(5):281-6. doi: 10.3727/096504014X13890370410249.
Histone deacetylase (HDAC) inhibitors have been shown to enhance the effects of 5-fluorouracil (5-FU) against various cancer cells; however, no report has shown that an HDAC inhibitor may enhance the effects of 5-FU with radiation. Therefore, we investigated whether the novel HDAC inhibitor OBP-801/YM753 could enhance the effects of 5-FU with radiation on esophageal squamous carcinoma KYSE170 cells. The inhibition of the cell growth was significantly stronger with the combination of OBP-801/YM753 with 5-FU than with the 5-FU treatment only. Furthermore, inhibition of the colony formation was the most effective with the combined treatment of OBP-801/YM753, 5-FU, and radiation. Western blot analysis showed that OBP-801/YM753 suppressed the expression of thymidylate synthase induced by 5-FU. Therefore, this three-combined therapy is promising for patients with esophageal squamous carcinoma.
2.A novel HDAC inhibitor OBP-801 and a PI3K inhibitor LY294002 synergistically induce apoptosis via the suppression of survivin and XIAP in renal cell carcinoma.
Yamada T1, Horinaka M, Shinnoh M, Yoshioka T, Miki T, Sakai T. Int J Oncol. 2013 Oct;43(4):1080-6. doi: 10.3892/ijo.2013.2042. Epub 2013 Jul 30.
Renal cell carcinoma (RCC) is resistant to traditional cancer therapies such as radiation therapy and chemotherapy. The use of targeted therapies has improved the clinical outcomes of patients with metastatic RCC. However, most patients acquire resistance against targeted therapies over time. We report that the combination of the novel histone deacetylase (HDAC) inhibitor OBP-801, also known as YM753 and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 synergistically inhibits cell growth and induces apoptosis in RCC cells. This combination activated caspase-3, -8 and -9 and the pan-caspase inhibitor zVAD-fmk significantly reduced the apoptotic response to the treatment with OBP-801 and LY294002. Moreover, the combined treatment induced intracellular reactive oxygen species (ROS) and the radical scavenger N-acetyl-L-cysteine (NAC) blocked the intracellular ROS and apoptosis induced by OBP-801 and LY294002. The co-treatment with OBP-801 and LY294002 markedly decreased survivin and the X-linked inhibitor of apoptosis protein (XIAP) protein levels, but Bcl-2 family members were not altered by the OBP-801/LY294002 co-treatment.
3.Combination of a novel HDAC inhibitor OBP-801/YM753 and a PI3K inhibitor LY294002 synergistically induces apoptosis in human endometrial carcinoma cells due to increase of Bim with accumulation of ROS.
Yoshioka T1, Yogosawa S, Yamada T, Kitawaki J, Sakai T. Gynecol Oncol. 2013 May;129(2):425-32. doi: 10.1016/j.ygyno.2013.02.008. Epub 2013 Feb 9.
OBJECTIVE: In most endometrial carcinoma, it has been observed that the PI3K/Akt pathway is abnormally accelerated in association with mutations in PIK3CA and PTEN. The present study aimed to examine the combined effect of a novel histone deacetylase (HDAC) inhibitor OBP-801/YM753 and a PI3K inhibitor LY294002 against human endometrial carcinoma cells.
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CAS 328548-11-4 OBP-801

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