产品
编 号：F752503
分子式：C25H27N7OS
分子量：473.59
分子式：C25H27N7OS
分子量：473.59
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CAS No: 2416844-79-4
产品详情
生物活性：
IHMT-TRK-284 (Compound 34) is a potent, orally active type II TRK kinase inhibitor with IC50 values of 10.5, 0.7, and 2.6 nM to TRKA, B, and C respectively. IHMT-TRK-284 displays great selectivity profile in the kinome and good in vivo antitumor efficacies.
体内研究：
IHMT-TRK-284 (Compound 34) (40 and 80 mg/kg; p.o.; daily, 10 days) shows good in vivo PK and antitumor efficacy properties.Animal Model:Four-week old female nu/nu mice, one million BaF3-TELTRKA, BaF3-TEL-TRKB, BaF3-TEL-TRKC, BaF3-LMNA-TRKA-F589L, BaF3-LMNA-TRKA-G667S, and five million KM-12-LUC cells in DMEM medium were formulated as a 1:1 mixture with matrigel and injected into the subcutaneous space on the right flank of nu/nu mice
Dosage:40 mg/kg and 80 mg/kg
Administration:Daily oral gavage, 10 days
Result:Dose-dependently inhibited the BaF3-TEL-TRKA, BaF3-TEL-TRKB, and BaF3-TEL-TRKC tumor progression with TGI (tumor growth inhibition) of 68%, 93%, and 58%. Dose-dependently inhibited the tumor progression and exhibited the TGI of 93% at 40 mg/kg/day and 95% at 80 mg/kg/day in KM-12-LUC cells inoculated xenograft mouse model. Potently inhibited the tumor growth with TGI values of 88% and 89% respectively at 80 mg/kg dosage in BaF3- LMNA-TRKA-F589L and BaF3-LMNA-TRKA-G667S cells.
Animal Model:Mice, sprague dawley rats, and beagle dogs
Dosage:1 mg/kg and 10 mg/kg
Administration:Intravenous injection and oral administration (Pharmacokinetic Analysis)
Result:Pharmacokinetic study of IHMT-TRK-284 in mice, sprague dawley rats, and beagle dogsaParameterMicei.v. (1 mg/kg) Micep.o. (10 mg/kg) Ratsi.v. (1 mg/kg) Ratsp.o. (10 mg/kg) Beagle Dogsi.v. (1 mg/kg) Beagle Dogsp.o. (10 mg/kg)
AUC(0-t)(ng/mL*h)7481431393952323464
Tmax (h)0.0331.50.034.7 0.084.3
T1/2 (h)2.63.42.72.50.0311.8
Vz (mL/kg)4934315679682
体外研究：
IHMT-TRK-284 (Compound 34) (0-10 μM, 72 h) shows antiproliferative effects against BaF3 cells, a panel of kinase transformed BaF3 cells, and KM-12-LUC cells.IHMT-TRK-284 (0-10 μM, 24 h) induces apoptosis and arrests the cell cycle into G0/G1 phase in KM-12-LUC cells.IHMT-TRK-284 exerts its inhibitory effect to the colon cancer cells through on-target inhibition of TRK.IHMT-TRK-284 could overcome drug resistant mutants including V573M and F589L in the ATP binding pocket as well as G667C/S in the DFG region.IHMT-TRK-284 shows selectivity over VEGFR2 kinase.
IHMT-TRK-284 (Compound 34) is a potent, orally active type II TRK kinase inhibitor with IC50 values of 10.5, 0.7, and 2.6 nM to TRKA, B, and C respectively. IHMT-TRK-284 displays great selectivity profile in the kinome and good in vivo antitumor efficacies.
体内研究：
IHMT-TRK-284 (Compound 34) (40 and 80 mg/kg; p.o.; daily, 10 days) shows good in vivo PK and antitumor efficacy properties.Animal Model:Four-week old female nu/nu mice, one million BaF3-TELTRKA, BaF3-TEL-TRKB, BaF3-TEL-TRKC, BaF3-LMNA-TRKA-F589L, BaF3-LMNA-TRKA-G667S, and five million KM-12-LUC cells in DMEM medium were formulated as a 1:1 mixture with matrigel and injected into the subcutaneous space on the right flank of nu/nu mice
Dosage:40 mg/kg and 80 mg/kg
Administration:Daily oral gavage, 10 days
Result:Dose-dependently inhibited the BaF3-TEL-TRKA, BaF3-TEL-TRKB, and BaF3-TEL-TRKC tumor progression with TGI (tumor growth inhibition) of 68%, 93%, and 58%. Dose-dependently inhibited the tumor progression and exhibited the TGI of 93% at 40 mg/kg/day and 95% at 80 mg/kg/day in KM-12-LUC cells inoculated xenograft mouse model. Potently inhibited the tumor growth with TGI values of 88% and 89% respectively at 80 mg/kg dosage in BaF3- LMNA-TRKA-F589L and BaF3-LMNA-TRKA-G667S cells.
Animal Model:Mice, sprague dawley rats, and beagle dogs
Dosage:1 mg/kg and 10 mg/kg
Administration:Intravenous injection and oral administration (Pharmacokinetic Analysis)
Result:Pharmacokinetic study of IHMT-TRK-284 in mice, sprague dawley rats, and beagle dogsaParameterMicei.v. (1 mg/kg) Micep.o. (10 mg/kg) Ratsi.v. (1 mg/kg) Ratsp.o. (10 mg/kg) Beagle Dogsi.v. (1 mg/kg) Beagle Dogsp.o. (10 mg/kg)
AUC(0-t)(ng/mL*h)7481431393952323464
Tmax (h)0.0331.50.034.7 0.084.3
T1/2 (h)2.63.42.72.50.0311.8
Vz (mL/kg)4934315679682
体外研究：
IHMT-TRK-284 (Compound 34) (0-10 μM, 72 h) shows antiproliferative effects against BaF3 cells, a panel of kinase transformed BaF3 cells, and KM-12-LUC cells.IHMT-TRK-284 (0-10 μM, 24 h) induces apoptosis and arrests the cell cycle into G0/G1 phase in KM-12-LUC cells.IHMT-TRK-284 exerts its inhibitory effect to the colon cancer cells through on-target inhibition of TRK.IHMT-TRK-284 could overcome drug resistant mutants including V573M and F589L in the ATP binding pocket as well as G667C/S in the DFG region.IHMT-TRK-284 shows selectivity over VEGFR2 kinase.
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