Pyrotinib (SHR-1258, BLTN, Pyrroltinib) dimaleate is a potent and selective irreversible dual tyrosine kinase inhibitor of EGFR and HER2 with IC50 of 0.013 μM and 0.038 μM, respectively.
Pyrotinib (SHR-1258, BLTN, Pyrroltinib) dimaleate is a potent and selective irreversible dual tyrosine kinase inhibitor of EGFR and HER2 with IC50 of 0.013 μM and 0.038 μM, respectively.
Pyrotinib (SHR1258), as an EGFR/HER2 dual tyrosine kinase inhibitor, shows excellent in vitro potency, selectivity, and favorable PK profiles.[1]
Pyrotinib (SHR1258) displays robust anti-tumor effects on HER2-overexpressing xenograft models and sufficiently safety windows in animals as well as favorable pharmacokinetic properties in human.[1]
[1] Xin Li, et al. Eur J Pharm Sci. 2017 Dec 15;110:51-61.
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Cell experiment: |
Cancer cells (A431, SK-BR-3 and NCI-N87) are treated at a suitable concentration of Pyrotinib for 72 hours. Cell proliferation is determined by a sulforhodamine B (SRB) method. The IC50 values are calculated by the data of inhibition rates of serial concentrations of Pyrotinib dimaleate[1]. |
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Animal experiment: |
Rats[1] Sprague Dawley (SD) rats (200-250g, 3 males and 3 females) are used .Test compounds (include Pyrotinib dimaleate) are administrated in both intravenous ( i.v. ; 3 mg/kg) and intragastric ( i.g. ;3 mg/kg) for rats to obtain their bioavailability. Plasma samples of nude mice is collected at pre-dose and 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h after the IV administration [1].Mice[1]: In vivo efficacy studies are performed on BALB/Ca-nude mice (6 to 7 weeks, female) from SLAC. Nude mice are hypodermic inoculated BT-474 human breast cancer cell or SK-OV-3 ovarian cancer cell. After tumor grows to 150-250 mm3, mice are randomly divided into groups and dosed with Pyrotinib (2.5, 5, 10, 20 mg/kg) once daily. The volume of tumors and the weight of the mice are measured and recorded for 2-3 times per weeks[1]. |
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参考文献: [1]. Li X, et al. Discovery and development of Pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur J Pharm Sci. 2017 Jan 21. pii: S0928-0987(17)30043-X. |
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