Lusutrombopag (S-888711)

Cell lines

pro-B-cell line(Ba/F3-hMpl cells，Ba/F3-mMpl cells)

Preparation Method

Cells were cultured with Lusutrombopag for 72 h. 10 µL WST-8 reagent as added to each well during the last 2–8 hours of culture. The absorbance was measured at a wavelength of 450 nm using a 96-well microplate reader.Then cell viability was evaluated by proliferation assay.

Reaction Conditions

pro-B-cell line were treated with Lusutrombopag (4.88–5000 nmol/L)for 72 h.

Applications

Lusutrombopag promoted the proliferation of Ba/F3-hMpl cells. The 50% EC50 values of lusutrombopag in Ba/F3-hMpl cells were 84.0 nmol/L,whereas lusutrombopag exhibited no proliferative activity in Ba/F3-mMpl cells.These results indicate that lusutrombopag promotes the proliferation of Ba/F3-hMpl cells via human c-Mpl.

Animal models

Thrombocytopenia patients with hepatocellular carcinoma or chronic liver disease.

Preparation Method

Patients were randomized in a 1:1 ratio to receive either lusutrombopag or placebo once daily for 7 days or fewer before an invasive procedure performed 9 to 14 days after randomization.

Dosage form

3mg/day, oral

Applications

Lusutrombopag reduced the need for platelet transfusions, increased platelet counts for 3 weeks, and reduced the number of bleeding events in patients with and without HCC compared with placebo. Risk of thrombosis was similar to that of placebo.

References:

[1]. Yoshida H, Yamada H, et al. Development of a new knock-in mouse model and evaluation of pharmacological activities of lusutrombopag, a novel, nonpeptidyl small-molecule agonist of the human thrombopoietin receptor c-Mpl. Exp Hematol. 2018 Mar;59:30-39.e2.

[2]. Alkhouri N, Imawari M, et al. Lusutrombopag Is Safe and Efficacious for Treatment of Thrombocytopenia in Patients With and Without Hepatocellular Carcinoma. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2600-2608.e1.