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JSH-150

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产品价格:电议      采购度:151      原产地:美洲

发布时间:2023/12/4 16:32:13      所属地区:国外 国外

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JSH-150 是一种高效的选择性 CDK9 抑制剂, IC50 为 1 nM。

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JSH-150

CAS No. : 2247481-21-4

MCE 站:JSH-150

产品活性:JSH-150 是一种高效的选择性 CDK9 抑制剂, IC50 为 1 nM。

研究领域:Cell Cycle/DNA Damage

作用靶点:CDK

In Vitro: The antiproliferative effect of JSH-150 is examined ton a panel of established cancer cell lines. JSH-150 exhibits potent antiproliferative activities in solid tumor cell lines such as A375 (melanoma), A431 (squamous), BE(2)M17 (neuroblastoma), GIST-T1 (GIST) and COLO205 (colon cancer) with GI50 values from 0.002 to 0.044 M. In the leukemia cell lines including acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and B cell lymphoma cell lines, JSH-150 also displays strong growth inhibition efficacies with GI50s ranging from single to double digit nM. In addition, JSH-150 is much less sensitive in normal CHO cells (GI50: 1.1 M) compared with the cancer cell lines.

In Vivo: Treatment of JSH-150 at all dosages, i.e., 10, 20 and 30 mg/kg/day, can almost completely suppress the tumor progression in the first two weeks and does not affect the animal’s weight indicating that there is no general cytotoxicity at these doses. After stopping the treatment of JSH-150, the tumors of the animals treated with 10 mpk drug dosage start to grow again. However, this tumor recurrence is not observed in the 20 and 30 mpk dosage groups during the following week after administration of JSH-150 is stopped and p values are quantified on the 21st day, which are 0.042, 0.0035 and 0.0028, respectively. The PK properties of JSH-150 are evaluated in different species including mice, Sprague-Dawley rats and beagle dogs through intravenous injection and oral administration. JSH-150 is absorbed rapidly in dogs and mice (Tmax=1.33 h and 2.00 h respectively) but slowly in rats (Tmax=3.33 h). JSH-150 also displays different half-lives in three different species via oral administration (T1/2=1.55 h in mice, 3.37 h in rats and 20.37 h in dogs), which indicates that it is metabolized very slowly in dogs compared with mice and rats. In addition, JSH-150 exhibits acceptable bioavailability in mice, rats and dogs (F=45.01%, 45.10% and 39.15%, respectively). The PK properties indicated that JSH-150 is suitable for oral administration.

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更新时间:2024/1/2 10:32:24

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