当9号染色体上的ABL基因与22号染色体上的BCR基因结合时，形成BCR-ABL融合基因。BCR-ABL被翻译成具有致癌性的组成型活性酪氨酸激酶。根据融合位置的不同，形成了分子量范围为185-210 kDa的多种蛋白质变体。BCR-ABL激活JAK/STAT通路和MAPK信号。[3]这种基因在大多数慢性髓性白血病(CML)患者中发现，在一些急性淋巴细胞白血病(ALL)或急性髓性白血病(AML)患者中发现。 Ponatinib是第二代BCR-Abl激酶的pan抑制剂，对BCR-Abl (T315I)的突变形式也有效。野生型和突变型的[1，2] IC50分别为0.5和11 nM。[4]在体外，Ponatinib还抑制几种其他临床相关激酶(RET、FLT3、KIT、PDGFRα、PDGFRβ和FGFR1)，在Ba/F3细胞系中的IC50s为5、25、100、5、9和23。[4]

产品性质：

Cas No.:943319-70-8

别名:普纳替尼; AP24534

化学名: 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide

Canonical SMILES CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CN=C5N4N=CC=C5

分子式:C29H27F3N6O

分子量:532.56

溶解度:≥ 53.3mg/mL in DMSO

储存条件:Store at -20°C

注意事项：

为了您的安全和健康，请穿实验服并戴一次性手套操作。

References:

1. Huang WS, Metcalf CA, Sundaramoorthi R, Wang Y, Zou D, Thomas RM, Zhu X, Cai L, Wen D, Liu S, Romero J, Qi J, Chen I, Banda G, Lentini SP, Das S, Xu Q, Keats J, Wang F, Wardwell S, Ning Y, Snodgrass JT, Broudy MI, Russian K, Zhou T, Commodore L, Narasimhan NI, Mohemmad QK, Iuliucci J, Rivera VM, Dalgarno DC, Sawyer TK, Clackson T, Shakespeare WC (June 2010). Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant. J. Med. Chem. 53 (12): 4701–19.

2. O'Hare T, Pollock R, Stoffregen EP, Keats JA, Abdullah OM, Moseson EM, Rivera VM, Tang H, Metcalf Ca CA, Bohacek RS, Wang Y, Sundaramoorthi R, Shakespeare WC, Dalgarno D, Clackson T, Sawyer TK, Deininger MW, Druker BJ (2004). Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood 104 (8): 2532–2539.

3. Cilloni D and Saglio G. Molecular pathways: BCR-ABL. Clinical Cancer Res (2011) 18(4):930-937

4. Gozgit JM, Wong MJ, Zhu X, Schrock AB, Chen T, Clackson T and Rivera VM. Ponatinib, a potent pan-BCR-ABL inhibitor, retains activity against gatekeeper mutants of FLT3, RET, KIT, PDGFR α/β and FGFR1. 2012 AACR poster.