产品
编 号：F750689
分子式：C31H29F3N8O2
分子量：602.61
分子式：C31H29F3N8O2
分子量：602.61
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CAS No: 2259657-48-0
产品详情
生物活性：
RET-IN-16 is a potent and selective RET inhibitor with IC50s of 3.98 nM, 8.42 nM, 15.05 nM, 7.86 nM, 5.43 nM and 8.86 nM for RET(WT), RET(M918T), RET(V804L), RET(V804M), RET-CCDC6 and RET-KIF5B, respectively. RET-IN-16 has anticancer effects.
体内研究：
RET-IN-16 (1 mg/kg; IV; single) exhibits a good drug exposure (AUC0-t = 6959 ± 762 ng·h/mL) and a moderate half-life (T1/2 = 4.28 ± 0.43 h).RET-IN-16 (10 mg/kg; PO; single) exhibits a low maximum plasma concentration (Cmax = 194 ± 47 ng·h/mL) and drug exposure (AUC0-t = 2112 ± 117 ng·h/mL).RET-IN-16 (30 and 50 mg/kg; IV; daily; for 8 days) suppresses tumor growth in a dose-dependent manner, and significantly suppresses p-RET and p-SHC in both KIF5B-RET and KIF5B-RETV804M in tumor tissues, as well as significantly induces apoptosis in vivo.Pharmacokinetic Parameters of RET-IN-16 in male Sprague-Dawley rats.IV (1 mg/kg) PO (10 mg/kg)
T1/2 (h)4.28 ± 0.437.59 ± 1.02
Tmax (h)0.083 ± 00.75 ± 0.43
Cmax (ng/mL)6097 ± 623194 ± 47
AUC0-t (ng/mL·h)6959 ± 7622112 ± 117
AUC0-∞ (ng/mL·h)7014 ± 7532343 ± 157
F (%)3.0
Animal Model:Male Sprague-Dawley rats
Dosage:1 mg/kg for IV, 10 mg/kg for PO
Administration:IV and PO; single (Pharmacokinetic Analysis)
Result:Exhibited a good drug exposure (AUC0-t = 6959 ± 762 ng·h/mL) and a moderate half-life (T1/2 = 4.28 ± 0.43 h) at 1 mg/kg IV; observed a low maximum plasma concentration (Cmax = 194 ± 47 ng·h/mL) and drug exposure (AUC0-t = 2112 ± 117 ng·h/mL) at 10 mg/kg PO.
Animal Model:Half male and female BALB/c-nu mice (6-8 weeks; injected with KIF5B-RET Ba/F3 and KIF5B-RETV804M Ba/F3)
Dosage:30 and 50 mg/kg
Administration:IV; daily; for 8 days
Result:Suppressed tumor growth in a dose-dependent manner, and significantly suppressed p-RET and p-SHC in both KIF5B-RET and KIF5B-RETV804M in tumor tissues, as well as significantly induced apoptosis in vivo.
体外研究：
RET-IN-16 (compound 9x) (0.005-10 μM; 48 hours) exhibits potent activity against CCDC6-RET-Ba/F3 and KIF5B-RET-Ba/F3 with GI50 of 9 nM and 17 nM, respectively.RET-IN-16 (1 μM; 48 hours) selectively suppresses the proliferation of CCDC6-RET fusion cells.RET-IN-16 (50 and 100 μM; 4 hours) remarkably blocks the autophosphorylation of RET in KIF5B-RET and KIF5B-RETV804M Ba/F3 cells, and the phosphorylation of the adapter protein SHC is also inhibited with a dose-dependent manner.
RET-IN-16 is a potent and selective RET inhibitor with IC50s of 3.98 nM, 8.42 nM, 15.05 nM, 7.86 nM, 5.43 nM and 8.86 nM for RET(WT), RET(M918T), RET(V804L), RET(V804M), RET-CCDC6 and RET-KIF5B, respectively. RET-IN-16 has anticancer effects.
体内研究：
RET-IN-16 (1 mg/kg; IV; single) exhibits a good drug exposure (AUC0-t = 6959 ± 762 ng·h/mL) and a moderate half-life (T1/2 = 4.28 ± 0.43 h).RET-IN-16 (10 mg/kg; PO; single) exhibits a low maximum plasma concentration (Cmax = 194 ± 47 ng·h/mL) and drug exposure (AUC0-t = 2112 ± 117 ng·h/mL).RET-IN-16 (30 and 50 mg/kg; IV; daily; for 8 days) suppresses tumor growth in a dose-dependent manner, and significantly suppresses p-RET and p-SHC in both KIF5B-RET and KIF5B-RETV804M in tumor tissues, as well as significantly induces apoptosis in vivo.Pharmacokinetic Parameters of RET-IN-16 in male Sprague-Dawley rats.IV (1 mg/kg) PO (10 mg/kg)
T1/2 (h)4.28 ± 0.437.59 ± 1.02
Tmax (h)0.083 ± 00.75 ± 0.43
Cmax (ng/mL)6097 ± 623194 ± 47
AUC0-t (ng/mL·h)6959 ± 7622112 ± 117
AUC0-∞ (ng/mL·h)7014 ± 7532343 ± 157
F (%)3.0
Animal Model:Male Sprague-Dawley rats
Dosage:1 mg/kg for IV, 10 mg/kg for PO
Administration:IV and PO; single (Pharmacokinetic Analysis)
Result:Exhibited a good drug exposure (AUC0-t = 6959 ± 762 ng·h/mL) and a moderate half-life (T1/2 = 4.28 ± 0.43 h) at 1 mg/kg IV; observed a low maximum plasma concentration (Cmax = 194 ± 47 ng·h/mL) and drug exposure (AUC0-t = 2112 ± 117 ng·h/mL) at 10 mg/kg PO.
Animal Model:Half male and female BALB/c-nu mice (6-8 weeks; injected with KIF5B-RET Ba/F3 and KIF5B-RETV804M Ba/F3)
Dosage:30 and 50 mg/kg
Administration:IV; daily; for 8 days
Result:Suppressed tumor growth in a dose-dependent manner, and significantly suppressed p-RET and p-SHC in both KIF5B-RET and KIF5B-RETV804M in tumor tissues, as well as significantly induced apoptosis in vivo.
体外研究：
RET-IN-16 (compound 9x) (0.005-10 μM; 48 hours) exhibits potent activity against CCDC6-RET-Ba/F3 and KIF5B-RET-Ba/F3 with GI50 of 9 nM and 17 nM, respectively.RET-IN-16 (1 μM; 48 hours) selectively suppresses the proliferation of CCDC6-RET fusion cells.RET-IN-16 (50 and 100 μM; 4 hours) remarkably blocks the autophosphorylation of RET in KIF5B-RET and KIF5B-RETV804M Ba/F3 cells, and the phosphorylation of the adapter protein SHC is also inhibited with a dose-dependent manner.
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