KRCA-0008

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Chemical Structure| 1472795-20-2 同义名 : -
CAS号 : 1472795-20-2
货号 : A503888
分子式 : C30H37ClN8O4
纯度 : 98%+
分子量 : 609.119
MDL号 : MFCD28133395
存储条件：

Pure form Keep in dark place,Inert atmosphere,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 200 mg/mL(328.34 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
描述 Anaplastic lymphoma kinase (ALK) belongs to the insulin receptor superfamily of tyrosine kinase. ALK-fused genes such as NPMALK, EML4-ALK, KIF5-ALK are putative oncogenes and responsible for many cancers including anaplastic large-cell lymphomas (ALCL), inflammatory myofibroblastic tumors (IMT), diffuse large B cell lymphoma (DLBCL) and a variety of solid tumor types [2]. KRCA-0008 is selective and potent to ALK and Ack1 with IC50 of 12 nM, 4 nM respectively, and has drug-like properties without hERG concerns [3].KRCA-0008 has good water-solubility with moderate plasma protein binding (93% in rat) and low brain exposure (Cbrain /C plasma =~0.02). It has good liver microsomal stability (% remaining after 30 min: 52% in mouse, 89% in rat, 72% inhuman). It does not appear to cause hERG blockade (patch clamp IC50=30 μM) and is negative on Ames test (1000 μg/plate), chro-mosomal aberration assay and micronucleus assay. KRCA-0008 also shows promising pharmacokinetic parameters in both mice and rat (oral bioavailability = 66–94.5%). Finally, KRCA-0008 shows a modest tumor growth inhibition in vivo activity in H3122 human lung cancer bearing mice model comparable to Crizotinib without significant body weight change. The KRCA-0008 25 mpk and 50 mpk groups did not show dose-dependent tumor growth inhibition. [2].
作用机制 Ligand interactions of KRCA-0008 display two hydrogen bonds with the backbone amide hydrogen and carbonyl oxygen of M1199 in the hinge region. The chlorine on the B-ring C5 position has hydrophobic interaction to L1196 as well as B-ring has CH/Π interaction with A1148 [4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.64mL

0.33mL

0.16mL

8.21mL

1.64mL

0.82mL

16.42mL

3.28mL

1.64mL
参考文献

[1]Park CH, Choe H, et al. Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) as potent and selective ALK inhibitors for anticancer treatment. Bioorg Med Chem Lett. 2013 Nov 15;23(22):6192-6.

[2] Park CH. Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) as potent and selective ALK inhibitors for anticancer treatment. Bioorg Med Chem Lett. 2013 Nov 15;23(22):6192-6.

[3]Park CH. Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) as potent and selective ALK inhibitors for anticancer treatment. Bioorg Med Chem Lett. 2013 Nov 15;23(22):6192-6.

[4]Lee HJ. ALK inhibitors of bis-ortho-alkoxy-para-piperazinesubstituted-pyrimidines and -triazines for cancer treatment. Arch Pharm Res. 2014;37(9):1130-8.