GW2580

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 c-Fms (CSF1R) 抑制剂，可在体外以 60 nM 浓度完全抑制人 cFMS 激酶。

A potent, selective c-Fms (CSF1R) inhibitor that completely inhibits human cFMS kinase in vitro at 60 nM; 150- to 500-fold selective compared to 26 other kinases (cKIT, cSRC, EGFR, etc.); completely inhibits the growth of CSF-1-dependent mouse myeloid M-NFS-60 cells at 0.7 uM; inhibits LPS-induced TNF production in mice and orally bioavailable.(In Vitro):GW2580 completely inhibits the growth of CSF-1-dependent mouse myeloid M-NFS-60 cells at 0.7 μM. GW2580 at 0.8-1 μM completely blocks the ability of CSF-1 to induce the growth of mouse M-NFS60 myeloid cells and human monocytes.GW2580 causes a 30-40% inhibition of PTH-induced calcium release at 0.1-0.3 μM, with higher concentrations of 1, 3, and 10 μM completely inhibiting the PTH response.GW2580 inhibits CSF1R phosphorylation in RAW264.7 murine macrophages stimulated with 10 ng/mL with IC50 of approximately 10 nM.GW2580 also inhibits TRKA activity with IC50 of 0.88 μM.(In Vivo):GW2580 (Oral administration; 20 and 80 mg/kg) produces a dose-related decrease in the number of tumor cells, with the 80 mg/kg dose completely blocking tumor growth.GW2580 (Oral administration; 20 and 80 mg/kg) has gave maximal plasma concentrations of 1.4 and 5.6 μM, respectively.GW2580 (50 mg/kg; twice a day from days 0 to 21, 7 to 21, or 14 to 21) inhibits joint connective tissue and bone destruction in a 21-day adjuvant arthritis model.

GW2580 completely inhibits the growth of CSF-1-dependent mouse myeloid M-NFS-60 cells at 0.7 μM. GW2580 at 0.8-1 μM completely blocks the ability of CSF-1 to induce the growth of mouse M-NFS60 myeloid cells and human monocytes. GW2580 causes a 30-40% inhibition of PTH-induced calcium release at 0.1-0.3 μM, with higher concentrations of 1, 3, and 10 μM completely inhibiting the PTH response. GW2580 inhibits CSF1R phosphorylation in RAW264.7 murine macrophages stimulated with 10 ng/mL with IC50 of approximately 10 nM. GW2580 also inhibits TRKA activity with IC50 of 0.88 μM.

GW2580 (Oral administration; 20 and 80 mg/kg) produces a dose-related decrease in the number of tumor cells, with the 80 mg/kg dose completely blocking tumor growth. GW2580 (Oral administration; 20 and 80 mg/kg) has gave maximal plasma concentrations of 1.4 and 5.6 μM, respectively. GW2580 (50 mg/kg; twice a day from days 0 to 21, 7 to 21, or 14 to 21) inhibits joint connective tissue and bone destruction in a 21-day adjuvant arthritis model. Animal Model:Female C3H/HEN mice or female CD-1 nude mice weighing 22-26 g Dosage:20 and 80 mg/kg Administration:Oral administration Result:Produced a dose-related decrease in the number of tumor cells, with the 80 mg/kg dose completely blocking tumor growth.Animal Model:Female C3H/HEN mice or female CD-1 nude mice weighing 22-26 g Dosage:20 and 80 mg/kg (Pharmacokinetic Study)Administration:Oral administration Result:Had gave maximal plasma concentrations of 1.4 and 5.6 μM, respectively.

GW-2580

Tyrosine Kinase

CSF1R

c-Fms

Inflammation/Immunology

——

870483-87-7

366.4137

C20H22N4O3

>98% (HPLC)

DMSO: 17.5 mg/mL

NC1=NC=C(CC2=CC=C(OCC3=CC=C(OC)C=C3)C(OC)=C2)C(N)=N1

2,4-Pyrimidinediamine, 5-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]-

(-20℃)

With Ice Pack

≥ 2 years