Pyrotinib

Research use only, not for human use.

Pyrotinib (SHR-1258)?is a potent and selective EGFR/HER2 dual inhibitor with IC50 of 13/38 nM, respectively.

Pyrotinib (SHR-1258)?is a potent and selective EGFR/HER2 dual inhibitor with IC50 of 13/38 nM, respectively; displays high selectivity in a panel of different kinases such as KDR, c-Kit, PDGFRβ, c-Src and c-Met (c-Src with an IC50 of 790 nM, and others >3,000 nM); exhibits robust anti-tumor effects on HER2-overexpressing xenograft models and sufficiently safety windows in animals as well as favorable pharmacokinetic properties in human.Breast Cancer Phase 3 Clinical(In Vitro):Pyrotinib has high potency in HER2-dependent cell lines (BT474, SK-OV-3), while showing much weaker inhibition in the HER2 negative cell line (MDA-MB-231). It inhibits BT474 and SK-OV-3Pyrotinib cells with IC50s of 5.1 and 43 nM, respectively. Pyrotinib displays high selectivity as HKI-272 when tested in a panel of different kinases such as KDR, c-Kit, PDGFRβ, c-Src and C-Met (c-Src with an IC50 of 790 nM, and others over 3000 nM).(In Vivo):Pyrotinib has acceptable bioavailability of 20.6%, 43.5% and 13.5% in nude mice, rats and dogs, respectively. Pyrotinib has favorable drug-like physicochemical properties and shows relatively higher oral exposure in human subjects with a much longer half life than that of preclinical animal species such as mouse, rat and dog. The TGI % (tumor growth inhibition) of Pyrotinib on day 21 is 109%, 157%, 159% at the doses of 5 mg/kg, 10 mg/kg, 20 mg/kg respectively. Pyrotinib in SK-OV-3 ovarian xenograft model shows TGI% on day 21 of 2%, 12%, 83% at the doses of 2.5 mg/kg, 5 mg/kg, 10 mg/kg respectively), which further confirms its robust?in vivo?antitumor efficacy at 10 mg/kg.

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SHR-1258 | SHR1258

Angiogenesis

EGFR

EGFR

Cancer

Breast Cancer

1269662-73-8

583.089

C32H31ClN6O3

>98% (HPLC)

DMSO : 0.172 mg/mL 0.29 mM

CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)C=CC5CCCN5C

(R,E)-N-(4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)-3-(1-methylpyrrolidin-2-yl)acrylamide

(-20℃)

With Ice Pack

≥ 2 years