Tirabrutinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的、选择性的、第三代不可逆突变 EGFR 抑制剂。

A potent, selective, third-generation irreversible inhibitor of mutant EGFR with IC50s of 1/12/5 nM for L858R-T790M/L858R/L861Q respectively; weak activity against wt EGFR (IC50=184 nM); inhibits signaling pathways and cellular growth in both EGFRm(+) and EGFRm(+)/T790M(+) mutant cell lines in vitro; exhibits tumor regression in EGFR-mutant tumor xenograft and transgenic models; orally active.Blood Cancer Phase 3 Clinical.

Tirabrutinib (0.1-1000 nM or 0.001-100 nM; 72 h) inhibits the proliferation of OCI-L Y10 and SU-DHL-6 cells with IC50s of 9.127 nM, and 17.10 nM, respectively.Tirabrutinib (0.5, 5, 50 μM; 24, 48 h) induces SU-DHL-6 cells apoptosis needs high dosage and prolonged administration (concentration up to 50 μM and incubates for 48 h).Tirabrutinib (300 nM, 72 h) induces caspase-3 and PARP cleavage in TMD8 cells. Cell Proliferation Assay Cell Line:SU-DHL-6 and OCI-L Y10 cells Concentration:0.1-1000 nM; 0.001 nM-100 nM Incubation Time:72 h Result:Showed good anti-proliferative activity with IC50s of 9.127 nM, and 17.10 nM for OCI-L Y10 and SU-DHL-6 cells, respectively.Apoptosis Analysis Cell Line:SU-DHL-6 cells Concentration:0.5, 5, 50 μM Incubation Time:24, 48 h Result:Induced cell apoptosis when concentration up to 50 μM and incubated for 48 h.Western Blot Analysis Cell Line:TMD8 cells Concentration:300 nM Incubation Time:72 hResult:Induced caspase-3 and PARP cleavage.

Tirabrutinib (10 mg/kg; p.o.; single) is rapidly absorbed into plasma and brain, and reaches Cmax (blood Cmax =339.53 ng/mL; brain Cmax =28.9 ng/mL) 2 hours post administration.Tirabrutinib (6, 20 mg/kg; p.o.; single daily for 3 weeks) shows inhibition of tumour growth in vivo. Animal Model:Male SD rats (219.0–260.5g).Animal Model:Immunodeficiency (SCID) mice (mouse xenograft model).Dosage:6, 20 mg/kg Administration:Oral administration; single daily for 3 weeks.Result:Inhibited tumour growth, and when dosage up to 20 mg/kg, a complete tumor suppression at day 14.

ONO4059 | ONO-4059 | GS4059 | GS 4059 | GS-4059

Tyrosine Kinase

BTK

BTK

Cancer

Blood cancer

1351636-18-4

454.4806

C25H22N6O3

>98% (HPLC)

10 mM in DMSO

CC#CC(=O)N1CCC(C1)N2C3=NC=NC(=C3N(C2=O)C4=CC=C(C=C4)OC5=CC=CC=C5)N

8H-Purin-8-one, 6-amino-7,9-dihydro-9-[(3R)-1-(1-oxo-2-butyn-1-yl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-

(-20℃)

With Ice Pack

≥ 2 years