S80001
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- 公司名稱 上海源葉生物科技有限公司
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- 更新時(shí)間 2024/7/2 19:52:16
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生物試劑,ELISA試劑盒,對(duì)照品,標(biāo)準(zhǔn)品,培養(yǎng)基,透析袋,病理科耗材,實(shí)驗(yàn)室耗材
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- 產(chǎn)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(duì)FLT3，ABL,，ABLT315I和 Aurora kinase 的 IC50 值分別為6.6,，14，4 和 48 nM,。
- 靶點(diǎn)： 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(nèi)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(xiàn)：
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(fù)凍融；-20℃,，1個(gè)月,；-80℃，6個(gè)月（稀釋后溶液溫度低保存可能會(huì)析出,，盡量現(xiàn)用現(xiàn)配）
細(xì)胞實(shí)驗(yàn):先用DMSO溶解：再用培養(yǎng)基進(jìn)行稀釋,，稀釋過(guò)程建議分段進(jìn)行，避免濃度變化過(guò)快導(dǎo)致化合物析出,。若稀釋過(guò)程中出現(xiàn)化合物析出的情況,， 可采用超聲的方法使其復(fù)溶。在稀釋時(shí)要確保工作液中 DMSO 的終濃度盡量在0.1%以下,，不要超過(guò)0.5%,，并設(shè)置相應(yīng)濃度的DMSO對(duì)照組。
動(dòng)物實(shí)驗(yàn)：先用DMSO溶解：再用水或者生理鹽水等去稀釋,，稀釋過(guò)程建議分段進(jìn)行,，避免濃度變化過(guò)快導(dǎo)致化合物析出。若稀釋過(guò)程中出現(xiàn)化合物析出的情況,， 可采用超聲的方法使其復(fù)溶,。可以通過(guò)添加助溶劑來(lái)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(qǐng)參考文獻(xiàn)。懸濁液可用于口服和腹腔注射,，不會(huì)影響產(chǎn)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
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