• PD 173074 selectively inhibits the tyrosine kinase activities of the FGF and VEGF receptors.
• PD 173074 inhibited the kinase activity of FGFR1 with an IC50 of 25 nM in vitro, while inhibiting Src, the receptors for insulin, epidermal growth factor (EGF) and PDGF, and several serine/threonine kinases with 1000-fold or higher IC50 values. PD 173074 was an ATP-competitive inhibitor of FGFR1, with a Ki of around 40 nM. PD 173074 inhibited autophosphorylation of FGFR1 and VEGFR2 in a dose-dependent manner with IC50s in the range of 1-5 nM and 100-200 nM, respectively. Mice treated daily with PD 173074 exhibited dose-dependent inhibition of FGF-induced and VEGF-induced neovascularization. However, PD 173074 was somewhat less effective in blocking VEGF-induced than FGF-induced angiogenesis. Mohammadi, M., et al. "Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain." EMBO J. 17: 5896-5904 (1998).
• PD 173074 inhibited cell proliferation of two low-grade, noninvasive human bladder urothelial carcinoma (UC) cell lines, UM-UC-14 and MGHU3, which expressed mutated FGFR3 protein. However, the other six cell lines expressing wild-type FGFR3 or without FGFR3 expression were resistant to PD 173074 treatment. In the mouse xenograft models subcutaneously transplanted with these two cell lines, orally administered PD173074 suppressed tumor growth and induced apoptosis. Miyake, M., et al. "1-tert-butyl-3-[6-(3,5-dimethoxy-phenyl)-2-(4-diethylamino-butylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea (PD173074), a selective tyrosine kinase inhibitor of fibroblast growth factor receptor-3 (FGFR3), inhibits cell proliferation of bladder cancer carrying the FGFR3 gene mutation along with up-regulation of p27/Kip1 and G1/G0 arrest." J. Pharmacol. Exp. Ther. 332: 795-802 (2010).
• The FGFR1 inhibitor PD 173074 dose-dependently inhibited FGF-2 promotion of granule neuron survival under low-potassium, serum-free conditions with IC50 of 12 nM, when added together with FGF-2 for a 24-h pretreatment prior to potassium withdrawal. Skaper, S.D., et al. "The FGFR1 inhibitor PD 173074 selectively and potently antagonizes FGF-2 neurotrophic and neurotropic effects." J. Neurochem. 75: 1520-1527 (2000).
• PD 173074 inhibited the proliferation and clonogenic growth of small cell lung cancer cell lines H-510 and H-69 in vitro and in vivo. It also prevented FGF-2-induced chemoresistance. These effects correlated with the inhibition of both FGFR1 and FGFR2 transphosphorylation. Pardo, O.E., et al. "The fibroblast growth factor receptor inhibitor PD173074 blocks small cell lung cancer growth in vitro and in vivo." Cancer Res. 69: 8645-8651 (2009).
• PD 173074 inhibited the growth of glioblastoma cells in vitro. Loilome, W., et al. "Glioblastoma cell growth is suppressed by disruption of Fibroblast Growth Factor pathway signaling." J. Neurooncol. 94: 359-366 (2009).
• Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.
• This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.
• Not available in some countries; not available to some institutions; not available for some uses.

M.W. 523.67
C28H41N7O3
[219580-11-7]

Storage

Store at or below -20 ºC

Solubility

Soluble in DMSO at 100 mg/mL; soluble in ethanol at 200 mg/mL; very poorly soluble in water; maximum solubility in plain water is estimated to be about 50-100 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility

Disposal

A LC Labs的关于纯度的更多信息我们知道许多情况下，由于不合格试剂的虚假结果，导致无法识别的纯度问题导致大量研究工作受到损害，甚至变得毫无用处。以下是信号转导试剂业务中产品纯度或活性问题的一些示例：几年前，一家主要的供应商向许多实验室提供了错误的激酶抑制剂H7异构体。错误的异构体具有明显不同的生物学特性，并且由此获得的结果也不正确。我们上级组织的科学家检测到了这个问题，并与一个合作的学术实验室一起发布了更正的数据[ Biochem。生物物理学。Res。通讯 187：657-663（1993）]。冈田酸产品存在很大的稳定性问题。冈田酸虽然散装形式相当稳定，但细分为亚毫克量并真空干燥以最终销售后，其降解率可立即高达40％或更高。许多供应商没有对包装后的最终产品进行适当的测试，我们的分析表明，其他一些供应商的冈田酸在某些情况下的纯度不足60％。客户一再告诉我们，冈田酸比其他供应商的原料更具活性。白屈菜红碱氯化物由于一些人们不了解的问题而引起了极大的动荡。首先，多年来，我们注意到白屈菜红碱的其他一些来源也被大量的生物活性杂质污染，例如血红碱，很难从天然来源的白屈菜红碱中去除。相比之下，我们的白屈菜红碱是通过严格的多步方法制备的，其中包括HPLC和结晶步骤，并且所得纯度极高且可重现。第二，研究人员告知我们，其他供应商的白屈菜红碱在不同批次之间显示出不同的生物活性。第三，在一些出版物中建议白屈菜红碱没有显示出最初归因于1991年的有效的PKC抑制活性[ Biochem.Chem.Soc。，1993，5，2，3]。生物物理学。Res。通讯 172：993-999（1991）]。1991年的这份报告使用了从天然来源分离的白屈菜红碱，它可能已经被抑制PKC催化活性的干扰化合物所污染。但是，可能不会排除其他更复杂的解释。但却是很清楚，白屈菜红有力块多效应的PKC活化剂，如佛波醇酯，但有可能的是，这些影响从PKC的相互作用，不涉及实际的激酶活性的抑制导致本身。据报道，1994年Rottlerin是PKCδ的选择性抑制剂，但最近的研究未能显示出在相似浓度下任何PKC抑制活性。1994年的研究使用了来自植物来源的rottlerin，当我们分析多个批次时，该物质一直被证明含有大量杂质。随后，非常有能力的实验室未能复制原始的rottlerin结果，以及其他考虑因素，迫使我们停止生产该产品。单击此处，可以在我们的rotterlin产品页面上找到更多信息。来自三个不同的非附属学术实验室的研究人员告知我们，我们的PMA在各种生物系统中的性能要优于从其他来源获得的材料。