Lestaurtinib

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

Lestaurtinib (KT-5555, CEP-701) 是一种有效的口服活性 JAK2、FLT3 和 TrkA 抑制剂，IC50 分别为 0.9 nM、3 nM 和 < 25 nM。

Lestaurtinib (KT-5555, CEP-701) is a potent, orally active JAK2, FLT3 and TrkA inhibitor with IC50 of 0.9 nM, 3 nM and < 25 nM, respectively; also inhibits Aurora A and B (IC50=8.1 and 2.3 nM); prevents STAT5 phosphorylation (IC50= 20-30 nM), exhibits antiproliferative activity in vitro (IC50=30-100 nM in HEL92.1.7 cells).Blood Cancer Phase 3 Clinical.

Lestaurtinib (0.01-10 μM; 72 h) inhibits growth of ATC cells, with IC50s of 0.21, 0.41 and 2.35 μM for KMH2, CAL62 and THJ-21T cells, respectively.Lestaurtinib (0.125-4 μM; 24 h) decreases STAT5 phosphorylation in a concentration-dependent manner, and completely inhibits expression of pSTAT5 at 4 μM.Lestaurtinib (0.5 μM; 24 h) shows antiproliferative effect on WI-38, CAL62 and KMH2 cells.Lestaurtinib (4 μM; 24 h) induces cell cycle arrest in the G2/M phase in CAL62 and KMH2 cells.Lestaurtinib (30-300 nM; 48 h) induces apoptosis in a dose-dependent manner in HL (hodgkin lymphoma) cell lines.Lestaurtinib (30, 100, 300 nM; 1 h) inhibits JAK2, STAT5 and STAT3 phosphorylation when at 300 nM. Cell Viability Assay Cell Line:KMH2, CAL62, THJ-21T cellsConcentration:0.01-10 μM Incubation Time:72 h Result:Showed good growth inhibitory activity with IC50s of 0.21, 0.41 and 2.35 μM for KMH2, CAL62 and THJ-21T cells, respectively.Cell Proliferation Assay Cell Line:WI-38, CAL62 and KMH2 cells Concentration:0.5 μMIncubation Time:24 h Result:Inhibited proliferation of ATC cells.Cell Cycle Analysis Cell Line:CAL62 and KMH2 cells Concentration:4 μM Incubation Time:24 h Result:Led to increase in the number of cells in the G2/M phase, and decrease in the number of cells in the G1/G0 and S phases (KMH2 cells more significant than CAL62 cells).Western Blot Analysis Cell Line:CAL62 cells Concentration:0.125-4 μM Incubation Time:24 h Result:Decreased pSTAT5 in a concentration-dependent manner, with a complete disappearance of pSTAT5 expression at 4 μM.Apoptosis Analysis Cell Line:L-428, L-1236, L-540, HDLM-2 and HDMY-Z cells Concentration:30-300 nM Incubation Time:48 h Result:Increased apoptosis rate of 62%, 57%, 10%, 64%, 30% for L-428, L-1236, L-540, HDLM-2 and HD-MY-Z cells respectively, when at 300 nM (in a dose-dependent manner).Western Blot Analysis Cell Line:L-428, L-1236, L-540, HDLM-2 and HD-MY-Z cells Concentration:30, 100, 300 nM Incubation Time:1 h Result:Decreased phospho-JAK2, -STAT5 and -STAT3 levels of all the HL cell lines by 46-94%, 88-100% and 97-100%, respectively (when at 300 nM).

Lestaurtinib (20 mg/kg; s.c.; twice daily (monday to friday) and once daily (saturday and sunday); 3 weeks) significantly inhibits growth of tumor in vivo. Animal Model:Four-week-old athymic nu/nu mice (SY5Y-TrkB xenografts model).Dosage:20 mg/kg Administration:Subcutaneous injection; twice daily (monday to friday) and once daily (saturday and sunday); 3 weeks.Result:Significantly slowed the growth of SY5Y-TrkB xenografts.

KT-5555 | CEP-701

Tyrosine Kinase

Trk Receptor

Trk Receptor

Cancer

Blood cancer

111358-88-4

439.46

C26H21N3O4

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (113.78 mM)

O=C1NCC(C2=C3N([C@]4(C)[C@](CO)(O)C[C@@]5([H])O4)C6=CC=CC=C62)=C1C7=C3N5C8=CC=CC=C78

(5R,7S,8S)-7-hydroxy-7-(hydroxymethyl)-5,6,7,8,13,14-hexahydro-15H-16-oxa-4b,8a,14-triaza-5,8-methanodibenzo[b,h]cycloocta[jkl]cyclopenta[e]-as-indacen-15-one

(-20℃)

With Ice Pack

≥ 2 years