CCX140

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、口服生物可利用的 CCR2 拮抗剂，对 hCCR2 的 Kd 为 2.3 nM。

A potent, selective, orally bioavailable CCR2 antagonist with Kd of 2.3 nM for hCCR2; displays little to no activity against 142 various biologically important receptor, no effect on plasma levels of the CCR2 ligand CCL2 or on the numbers of blood monocytes; potently inhibits CCL2-induced chemotaxis of purified human blood monocytes with IC50 of 8 nM, also inhibits CCL2-induced Ca2+ mobilization in monocytes with IC50 of 3 nM; decreases levels of fasting blood glucose and improves insulin sensitivity in mice.Diabetes Phase 2 Clinical.

CCX140 (CCX140-B) potently inhibits CCL2-induced chemotaxis of purified human blood monocytes with IC50 values of 8 nM in buffer and 200 nM in the presence of 100% human serum. CCX140 also inhibits CCL2-induced Ca2+ mobilization in monocytes with an IC50 value of 3 nM. CCX140 inhibits the binding of 125I-CCL2 to monocytes with an IC50 value of 17 nM. CCX140 has a Kd value of 2.3 nM toward hCCR2. CCX140 also inhibits monocyte chemotaxis mediated by the other CCR2 ligands: CCL8/MCP-2, CCL7/MCP-3, and CCL13/MCP-4.

Treatment of hCCR2 KI mice with CCX140 (CCX140-B) causes a dose-dependent reduction in the number of peritoneal leukocytes after thioglycollate challenge: CCX140 strongly blocks leukocyte infiltration at 30 mg/kg, partially blocks leukocyte infiltration at 10 mg/kg, and fails to block leukocyte infiltration at 3 mg/kg. In DIO hCCR2 KI mice, treatment with 100 mg/kg CCX140 blocks the progressive increase in UAER and ACR. CCX140 maintains lower UAER and ACR values during the entire 8-wk dosing regimen. In DIO mice, the CCR2 antagonist completely blocks the recruitment of inflammatory macrophages to visceral adipose tissue. The mice exhibit reduced hyperglycemia and insulinemia, improved insulin sensitivity, increased circulating adiponectin levels, decreased pancreatic islet size and increased islet number. CCX140 also reduces urine output, glucose excretion, hepatic glycogen and triglyceride content and glucose 6-phosphatase levels.

CCX-140 | CCX 140 | CCX140-B | CCX140B

GPCR/G Protein

Chemokine Receptor

Chemokine Receptor

Metabolic Disease

Diabetes

1100318-47-5

495.8621296

C20H13ClF3N5O3S

>98% (HPLC)

10 mM in DMSO

O=S(C1=CC=C(Cl)C(C(F)(F)F)=C1)(NC2=CC(C)=CN=C2C(C3=C4C(NC=C4)=NC=N3)=O)=O

Benzenesulfonamide, 4-chloro-N-[5-methyl-2-(7H-pyrrolo[2,3-d]pyrimidin-4-ylcarbonyl)-3-pyridinyl]-3-(trifluoromethyl)-

(-20℃)

With Ice Pack

≥ 2 years