Oritinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Oritinib 是一种 EGFR 抑制剂，对 EGFR (wt)、EGFR (L858R)、EGFR (L861Q)、EGFR (L858R/T790M)、EGFR (d746-750) 的 IC50 分别为 18、0.7、4、0.1、1.4 和 0.89 nM 、EGFR (d746-750/T790M)，分别。奥瑞替尼可用于治疗非小细胞肺癌的研究。

Oritinib is an inhibitor of EGFR with IC50s of 18, 0.7, 4, 0.1, 1.4 and 0.89 nM for EGFR (wt), EGFR (L858R), EGFR (L861Q), EGFR (L858R/T790M), EGFR (d746-750), EGFR (d746-750/T790M), respectively. Oritinib can be used in studies about the treatment of non-small cell lung cancer.(In Vitro):Oritinib (0.001, 0.01, 0.1, 1, and 10 μM) selectively inhibits EGFR-mutated NCI-H1975, H3255 and PC-9 cells, with IC50s of 3.932, 9.39 and 7.63 nM, respectively. Oritinib (0.1 μM) continuously inhibits the phosphorylation of EGFR in PC-9 and NCI-H1975 cells.(In Vivo):In female mice bearing NCI-H1975 and A431 xenograft models， Oritinib (2.5, 5, and 15 mg/kg; oral) significantly inhibits proliferation of tumor cells with no TKI-induced weight loss. In NCI-H1975 tumor-bearing mice, Oritinib (2.5, 5, and 15 mg/kg; oral) shows good bioavailability(Tmax = 1.5-2 h) and extensive distribution from the plasma to the tissues. The AUC0–t values in plasma are 118, 300 and 931 ng×h/mL on Day 1, while 272, 308 and 993 ng×h/ml on Day 14, respectively.

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. Cell Proliferation Assay 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).

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. 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 daysResult: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 Tmax is 1.5-2 h, indicating rapidly distributed into tissues, including lung tumor tissues. The AUC0–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.

SH-1028

Angiogenesis

EGFR

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2035089-28-0

539.67

C31H37N7O2

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (231.62 mM)

O=C(C=C)NC1=CC(NC=2N=CC=C(N2)C=3C=4C=CC=CC4N5C3CCCC5)=C(OC)C=C1N(C)CCN(C)C

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(-20℃)

With Ice Pack

≥ 2 years