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Derazantinib

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Chemical Structure| 1234356-69-4 同义名 : ARQ-087
CAS号 : 1234356-69-4
货号 : A267187
分子式 : C29H29FN4O
纯度 : 99%+
分子量 : 468.565
MDL号 : MFCD30532770
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(53.35 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • FGFR2

    FGFR2, IC50:1.8 nM

  • FGFR3

    FGFR3, IC50:4.5 nM

  • FGFR4

    FGFR4, IC50:34 nM

  • FGFR1

    FGFR1, IC50:4.5 nM
描述 Fibroblast growth factor receptor (FGFR) signaling plays an essential role in cellular proliferation, difference and migration. Derazantinib is a small-molecule kinase inhibitor for the FGFR family. It exhibits inhibitory activity against FGER2 with an IC50 of 1.8 nM and against FGFR1 and 3 with an IC50 of 4.5 nM. The Ki values of FGFR1 and FGFR2 were 2.7 nM and 0.68 nM, respectively. The autophosphorylation of the tyrosine residues of FGFR1 and FGFR2 were inhibited by derazantinib (0 - 5 μM) at a dose-dependent manner. Derazantinib also showed potent inhibitory functionality against other kinases, such as RET, DDR2, and FMS, with IC50 values of 3, 3.6 and 3.8, respectively. In COS-1 cells overexpressing FGFR1, FGFR2, FGFR3 and FGFR4, derazantinib inhibited the phosphorylation of FGFR1, FGFR2, FGFR3, and FGFR4 with EC50 values of <0.123 μM, 0.185 μM, 0.463 μM, and >10 μM respectively. Derazantinib inhibited multiple cell lines with FGFR1 or FGFR3 fusions with GI50 values between 0.13 - 1.4 μM. In SNU-16 tumor-bearing animals, oral administration of derazantinib (25, 50, 75 mg/kg) for 9 days reduced the phosphorylation of FGFR, FRS2-α, and ERK. Treatment of derazantinib at 50 mg/kg and 75 mg/kg for 15 days also demonstrated 69% and 83% tumor growth inhibition, respectively, in the Ba/F3-FGFR2 model[4].
作用机制 Derazantinib is a ATP-competitive inhibitor against FGFR. It contains a core structure, in which the aminopyrimidine moiety participates in a hinge interaction. Meanwhile, the hydrophobic region of the core stabilizes the downward G-loop conformation via non-polar interactions[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.13mL

0.43mL

0.21mL

10.67mL

2.13mL

1.07mL

21.34mL

4.27mL

2.13mL
参考文献

[1]Balek L, Gudernova I, et al. ARQ 087 inhibits FGFR signaling and rescues aberrant cell proliferation and differentiation in experimental models of craniosynostoses and chondrodysplasias caused by activating mutations in FGFR1, FGFR2 and FGFR3. Bone. 2017 Aug 18. pii: S8756-3282(17)30311-3.

[2]Chila R, Hall G T, et al. Multi-Chemotherapeutic Schedules Containing the pan-FGFR Inhibitor ARQ 087 are Safe and Show Antitumor Activity in Different Xenograft Models. Transl Oncol. 2017 Apr;10(2):153-157.

[3]Hall TG, Yu Y, et al. Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation. PLoS One. 2016 Sep 14;11(9):e0162594.

[4]Hall TG, Yu Y, Eathiraj S, Wang Y, Savage RE, Lapierre JM, Schwartz B, Abbadessa G. Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation. PLoS One. 2016 Sep 14;11(9):e0162594.