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Oritinib
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Oritinib图片
CAS NO:2035089-28-0
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
50mg电议
100mg电议

产品名称
SH-1028
产品介绍
SH-1028 是一种不可逆的第三代EGFR TKI,可克服 T790M 介导的非小细胞肺癌耐药。SH-1028 是 EGFR 激酶活性的突变选择性抑制剂,抑制EGFRWTEGFRL858REGFRL861QEGFRL858R/T790MEGFRd746-750EGFRd746-750/T790M激酶,IC50值分别为 18、0.7、4、0.1、1.4 和 0.89 nM。
生物活性

Oritinib (SH-1028), an irreversible third-generationEGFRTKI, overcomes T790M-mediated resistance in non-small cell lungcancer. Oritinib (SH-1028), a mutant-selective inhibitor ofEGFRkinase activity, inhibitsEGFRWT,EGFRL858R,EGFRL861Q,EGFRL858R/T790M,EGFRd746-750andEGFRd746-750/T790Mkinases, withIC50s of 18, 0.7, 4, 0.1, 1.4 and 0.89 nM, respectively[1].

IC50& Target[1]

EGFR (WT)

18 nM (IC50)

EGFRL858R

0.7 nM (IC50)

EGFRL861Q

4 nM (IC50)

EGFRL858R/T790M

0.1 nM (IC50)

EGFRd746-750

1.4 nM (IC50)

EGFRd746-750/T790M

0.89 nM (IC50)

体外研究
(In Vitro)

Oritinib (SH-1028) binds irreversibly to EGFR kinase by targeting cysteine-797 residue in the ATP binding site via covalent bond formation[1].
Oritinib (0.001-10 μM) potently and selectively targets mutant EGFR cell lines in vitro[1].
Oritinib (0.1 μM) continuously inhibits the phosphorylation of EGFR in PC-9 and NCI-H1975 cells at lower concentrations or even drug-free for at least 6 h[1].

Cell Proliferation Assay[1]

Cell Line:A431 (EGFRWT), H3255 (EGFRL858R), PC-9 (EGFRd746-750) and NCI-H1975 (EGFRL858R/T790M) cells
Concentration:0.001, 0.01, 0.1, 1, and 10 μM
Incubation Time:72 hours
Result:Selectively inhibited EGFR-mutated NCI-H1975, H3255 and PC-9 cells, with IC50s of 3.93±1.12, 9.39±0.88 and 7.63±0.18 nmol/L, respectively, which were about 198-, 83- and 102-fold more sensitive than the inhibition of wild-type EGFR in A431 cells (IC50=778.89±134.74 nM).
体内研究
(In Vivo)

Oral administration of Oritinib at a daily dose of 5 mg/kg significantly inhibits proliferation of tumor cells with EGFR sensitive mutation (exon 19 del) and resistant mutation (T790 M) for consecutive 14 days, with no TKI-induced weight loss in mouse xenograft models[1].
Oritinib shows good bioavailability, and is distributed extensively from the plasma to the tissues[1].

Animal Model:6-8 weeks old female mice bearing NCI-H1975 and A431 xenograft models[1]
Dosage:2.5, 5, and 15 mg/kg
Administration:Orally administrated once daily for consecutive 14 days
Result:Led to a significant inhibition of tumor cell growth in both PC-9 (exon 19 del) and NCI-H1975 (L858R/T790M) xenograft models.
Animal Model:NCI-H1975 tumor-bearing mice[1]
Dosage:2.5, 5, and 15 mg/kg (Pharmacokinetic Analysis)
Administration:Oral administration for 1 day or 14 consecutive days.
Result:The Tmaxis 1.5-2 h, indicating rapidly distributed into tissues, including lung tumor tissues.
The AUC0–tvalues in plasma were 118, 300 and 931 ng×h/mL on Day 1, while 272, 308 and 993 ng×h/ml on Day 14, respectively.
Clinical Trial
分子量

539.67

性状

Solid

Formula

C31H37N7O2

CAS 号

2035089-28-0

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder-20°C3 years
4°C2 years
In solvent-80°C6 months
-20°C1 month
溶解性数据
In Vitro: 

DMSO : 125 mg/mL(231.62 mM;Need ultrasonic)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM1.8530 mL9.2649 mL18.5298 mL
5 mM0.3706 mL1.8530 mL3.7060 mL
10 mM0.1853 mL0.9265 mL1.8530 mL
*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。