Pyrotinib

Controlled Substances

Psychoactive Drugs/Narcotic Drugs/Hypertoxic Chemicals/Non-Medical Use of Narcotic Drugs and Psychotropic Substances

Names

[ CAS No. ]:
1269662-73-8

[ Name ]:
Pyrotinib

[Synonym ]:
2-Propenamide, N-[4-[[3-chloro-4-(2-pyridinylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-3-[(2R)-1-methyl-2-pyrrolidinyl]-, (2E)-
PYROTINIB
(2E)-N-(4-{[3-Chloro-4-(2-pyridinylmethoxy)phenyl]amino}-3-cyano-7-ethoxy-6-quinolinyl)-3-[(2R)-1-methyl-2-pyrrolidinyl]acrylamide

Biological Activity

[Description]:

Pyrotinib (SHR-1258) is a potent and selective EGFR/HER2 dual inhibitor with IC50s of 13 and 38 nM, respectively.

[Related Catalog]:

Research Areas >> Cancer

[Target]

EGFR:13 nM (IC50)

HER2:38 nM (IC50)


[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)[1].

[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[1].

[Cell Assay]

Cancer cells (A431, SK-BR-3 and NCI-N87) are treated with a series of concentrations 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 test compounds[1].

[Animal admin]

Rats: Test compounds (include Pyrotinib) are administrated in both intravenous (i.v.) and intragastric (i.g.) for mice 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: 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 week[1].

[References]

[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.


[Related Small Molecules]

Osimertinib (AZD9291) | Tyrphostin B42 (AG-490) | Neratinib (HKI-272) | Genistein | (-)-Epigallocatechin gallate | AG-1478 | Dacomitinib (PF-00299804) | Irbinitinib | Poziotinib | Olmutinib | Sapitinib | AZD-3759 | Canertinib dihydrochloride | BMS-690514 | Pelitinib

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
775.5±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C32H31ClN6O3

[ Molecular Weight ]:
583.080

[ Flash Point ]:
422.8±32.9 °C

[ Exact Mass ]:
582.214600

[ LogP ]:
5.64

[ Vapour Pressure ]:
0.0±2.7 mmHg at 25°C

[ Index of Refraction ]:
1.677

[ Storage condition ]:
2-8℃


Related Compounds