Lusutrombopag (S-888711) |
| Catalog No.GC31669 |
Lusutrombopag, an orally bioavailable, small molecule thrombopoietin receptor agonist, is approved for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1110766-97-6
Sample solution is provided at 25 µL, 10mM.
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Lusutrombopag, an orally bioavailable, small molecule thrombopoietin receptor agonist, is approved for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure[1].
Lusutrombopag exhibits agonist activity for human thrombopoietin(TPO) receptor c-Mpl. Lusutrombopag promoted the proliferation of Ba/F3-hMpl cells. The 50% EC50 values of lusutrombopag Ba/F3-hMpl cells were 84.0, 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. To investigate the signal transduction pathway of lusutrombopag, we evaluated the phosphorylation of JAK2, STAT3, STAT5 and p44/42 MAPK in Ba/F3-hMpl cells. Lusutrombopag phosphorylated these molecules similarly to rhTPO. These results suggest that lusutrombopag activates the same signal transduction pathways activated by rhTPO[2]
Lusutrombopag significantly increased circulating platelets in a dose-dependent manner during 21-day repeated oral administration in TPOR-Ki/Shi mice, was developed by replacing mouse Mpl with human-mouse chimera Mpl. Histopathological study of the TPOR-Ki/Shi mice on day 22 also revealed a significant increase in megakaryocytes in the bone marrow. These results indicate that lusutrombopag acts on human TPOR to upregulate differentiation and proliferation of megakaryocytic cells, leading to platelet production[2]
Lusutrombopag significantly increased the platelet count in all 31 patients with a mean increase of 31,000/µL.However, the increase in the platelet count after platelet transfusion was not statistically significant. When 13 patients repeated uses of lusutrombopag were counted platelet transfusion was not required in 82.1% (23/28) of treatments[3]
References:
[1]. Shirley M, McCafferty EH, et al. Lusutrombopag: A Review in Thrombocytopenia in Patients with Chronic Liver Disease Prior to a Scheduled Procedure. Drugs. 2019 Oct;79(15):1689-1695.
[2]. 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.
[3]. Nomoto H, Morimoto N, et al. Lusutrombopag is effective and safe in patients with chronic liver disease and severe thrombocytopenia: a multicenter retrospective study. BMC Gastroenterol. 2020 Dec 14;20(1):427.
| Cell experiment [1]: | |
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 experiment [2]: | |
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: | |
| Cas No. | 1110766-97-6 | SDF | |
| Canonical SMILES | O=C(O)/C(C)=C/C1=C(Cl)C=C(C(NC2=NC(C3=CC=CC([C@@H](OCCCCCC)C)=C3OC)=CS2)=O)C=C1Cl | ||
| Formula | C29H32Cl2N2O5S | M.Wt | 591.55 |
| Solubility | DMSO : ≥ 33 mg/mL (55.79 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6905 mL | 8.4524 mL | 16.9047 mL |
| 5 mM | 0.3381 mL | 1.6905 mL | 3.3809 mL |
| 10 mM | 0.169 mL | 0.8452 mL | 1.6905 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 31 reference(s) in Google Scholar.)
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