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上海源葉生物科技有限公司
主營產品： S30260異硫氰酸胍,30259鹽酸胍,嗜熱菌蛋白酶 |
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15921386130
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- 聯系人：
- 何小姐
- 電話：
- 86-021-61559134
- 手機：
- 15921386130
- 傳真：
- 86-021-55068248
- 地址：
- 上海市松江區(qū)長塔路465號6幢
- 郵編：
- 200433
- 網址：
- www.shyuanye.com
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更新時間：2024-07-02 19:52:16瀏覽次數：163
聯系我們時請說明是化工儀器網上看到的信息，謝謝!
- 提示：詳情請下載說明書。
- 產品描述：
KW-2449 is a novel multikinase inhibitor, which suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Recent research showed that HDACIs increase KW-2449 lethality in Bcr/Abl(+) cells in association with inhibition of Bcr/Abl, generation of ROS, and induction of DNA damage. This strategy preferentially targets primary Bcr/Abl(+) hematopoietic cells and exhibits enhanced in vivo activity. Combining KW-2449 with HDACIs warrants attention in IM-resistant Bcr/Abl(+) leukemias. (source: Clin Cancer Res. 2011 May 15;17(10):3219-32. Epub 2011 Apr 7.).對FLT3，ABL，ABLT315I和 Aurora kinase 的 IC50 值分別為6.6，14，4 和 48 nM。
- 靶點： Abl；ABL-T315I;FGFR1;Aurora A;FLT3/D835Y;FLT3;JAK2;SRC;PDFGRα
- 體外研究： KW-2449 shows growth inhibitory activities against FLT3/ITD-, FLT3/D835Y-, and wt-FLT3/FL-expressing 32D cells, MOLM-13 and MV4;11 with GI50 values of 0.024, 0.046, 0.014, 0.024, and 0.011 μM, respectively. KW-2449 suppresses the phosphorylations of FLT3 (P-FLT3) and its downstream molecule phospho-STAT5 (P-STAT5) in MOLM-13 cells in a dose-dependent manner. KW-2449 increases the percentage of cells in the G1 phase of the cell cycle and reciprocally reduced the percentage of cells in the S phase, resulting in the increase of apoptotic cell population.
- 體內研究： Oral administration of KW-2449 shows dose-dependent and significant tumor growth inhibition in FLT3-mutated xenograft model with minimum bone marrow suppression. In FLT3 wild-type human leukemia, it induces the reduction of phosphorylated histone H3, G2/M arrest, and apoptosis. In imatinib-resistant leukemia, KW-2449 contributes to release of the resistance by the simultaneous down-regulation of BCR/ABL and Aurora kinases. Furthermore, the antiproliferative activity of KW-2449 is confirmed in primary samples from AML and imatinib-resistant patients. The inhibitory activity of KW-2449 is not affected by the presence of human plasma protein, such as α1-acid glycoprotein.
- 參考文獻：
1. Pratz, Keith W.; Sato, Takashi; Murphy, Kathleen M.; Stine, Adam; Rajkhowa, Trivikram; Levis, Mark. FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood (2010), 115(7), 1425-1432. CODEN: BLOOAW ISSN:0006-4971. AN 2010:301893
2. Shiotsu, Yukimasa; Kiyoi, Hitoshi; Akinaga, Shiro; Naoe, Tomoki. Screening of molecular target therapy of cancer and generation of new kinase inhibitor, KW-2449. Saibo (2009), 41(9), 381-384. CODEN: SAIBC7 ISSN:1346-7557. AN 2009:1319160
3. Verma, Dushyant; Kantarjian, Hagop M.; Jones, Dan; Luthra, Rajyalakshmi; Borthakur, Gautam; Verstovsek, Srdan; Rios, Mary Beth; Cortes, Jorge. Chronic myeloid leukemia (CML) with P190BCR-ABL: analysis of characteristics, outcomes, and prognostic significance. Blood (2009), 114(11), 2232-2235. CODEN: BLOOAW ISSN:0006-4971. CAN 152:188988 AN 2009:1173490
4. Shiotsu, Yukimasa; Kiyoi, Hitoshi; Ishikawa, Yuichi; Tanizaki, Ryohei; Shimizu, Makiko; Umehara, Hiroshi; Ishii, Kenichi; Mori, Yumiko; Ozeki, Kazutaka; Minami, Yosuke; Abe, Akihiro; Maeda, Hiroshi; Akiyama, Tadakazu; Kanda, Yutaka; Sato, Yuko; Akinaga, Shiro; Naoe, Tomoki. KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood (2009), 114(8), 1607-1617. CODEN: BLOOAW ISSN:0006-4971. CAN 151:462381 AN 2009:1081843
5. Pratz, Keith W.; Cortes, Jorge; Roboz, Gail J.; Rao, Niranjan; Arowojolu, Omotayo; Stine, Adam; Shiotsu, Yukimasa; S
- 溶解度： DMSO : 50 mg/mL
母液保存：分裝凍存，避免反復凍融；-20℃，1個月；-80℃，6個月（稀釋后溶液溫度低保存可能會析出，盡量現用現配）
細胞實驗:先用DMSO溶解：再用培養(yǎng)基進行稀釋，稀釋過程建議分段進行，避免濃度變化過快導致化合物析出。若稀釋過程中出現化合物析出的情況， 可采用超聲的方法使其復溶。在稀釋時要確保工作液中 DMSO 的終濃度盡量在0.1%以下，不要超過0.5%，并設置相應濃度的DMSO對照組。
動物實驗：先用DMSO溶解：再用水或者生理鹽水等去稀釋，稀釋過程建議分段進行，避免濃度變化過快導致化合物析出。若稀釋過程中出現化合物析出的情況， 可采用超聲的方法使其復溶?？梢酝ㄟ^添加助溶劑來幫助溶解，比如植物油、Tween80、甘油、羧甲基纖維素鈉和PEG400等。具體方式請參考文獻。懸濁液可用于口服和腹腔注射，不會影響產品活性。
- 保存條件： -20℃
- 配置溶液濃度參考：
1mg 5mg 10mg 1 mM 3.008 ml 15.042 ml 30.084 ml 5 mM 0.602 ml 3.008 ml 6.017 ml 10 mM 0.301 ml 1.504 ml 3.008 ml 50 mM 0.06 ml 0.301 ml 0.602 ml
- 注意：部分產品我司僅能提供部分信息，我司不保證所提供信息的性，僅供客戶參考交流研究之用。
