Oritinib SH-1028|cas:2035089-28-0|西域试剂

Oritinib SH-1028,99.18%

产品编号：Bellancom-139920| CAS NO：2035089-28-0| 分子式：C₃₁H₃₇N₇O₂| 分子量：539.67

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货号	包装	价格	库存与货期	购买量	操作
Bellancom-139920		￥5000.00	杭州北京（现货）
Bellancom-139920		￥8500.00	杭州北京（现货）

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Oritinib 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 EGFR^WT、EGFR^L858R、EGFR^L861Q、EGFR^L858R/T790M、EGFR^d746-750 和 EGFR^{d746-750/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-generation EGFR TKI, overcomes T790M-mediated resistance in non-small cell lung cancer. Oritinib (SH-1028), a mutant-selective inhibitor of EGFR kinase activity, inhibits EGFR^WT, EGFR^L858R, EGFR^L861Q, EGFR^L858R/T790M, EGFR^d746-750 and EGFR^{d746-750/T790M} kinases, with IC₅₀s of 18, 0.7, 4, 0.1, 1.4 and 0.89 nM, respectively.

体外研究

Oritinib (SH-1028) binds irreversibly to EGFR kinase by targeting cysteine-797 residue in the ATP binding site via covalent bond formation.
Oritinib (0.001-10 μM) potently and selectively targets mutant EGFR cell lines in vitro.
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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay

Cell Line:	A431 (EGFR^WT), H3255 (EGFR^L858R), PC-9 (EGFR^d746-750) and NCI-H1975 (EGFR^L858R/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.
Oritinib shows good bioavailability, and is distributed extensively from the plasma to the tissues.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	6-8 weeks old female mice bearing NCI-H1975 and A431 xenograft models
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
Dosage:	2.5, 5, and 15 mg/kg (Pharmacokinetic Analysis)
Administration:	Oral administration for 1 day or 14 consecutive days.
Result:	The T_max is 1.5-2 h, indicating rapidly distributed into tissues, including lung tumor tissues. The AUC_0–t values 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.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	6-8 weeks old female mice bearing NCI-H1975 and A431 xenograft models
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
Dosage:	2.5, 5, and 15 mg/kg (Pharmacokinetic Analysis)
Administration:	Oral administration for 1 day or 14 consecutive days.
Result:	The T_max is 1.5-2 h, indicating rapidly distributed into tissues, including lung tumor tissues. The AUC_0–t values 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.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	6-8 weeks old female mice bearing NCI-H1975 and A431 xenograft models
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
Dosage:	2.5, 5, and 15 mg/kg (Pharmacokinetic Analysis)
Administration:	Oral administration for 1 day or 14 consecutive days.
Result:	The T_max is 1.5-2 h, indicating rapidly distributed into tissues, including lung tumor tissues. The AUC_0–t values 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.

性状

Solid

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 mg	5 mg	10 mg

1 mM	1.8530 mL	9.2649 mL	18.5298 mL
5 mM	0.3706 mL	1.8530 mL	3.7060 mL
10 mM	0.1853 mL	0.9265 mL	1.8530 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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式