[CAS NO. 2247481-21-4] JSH-150
PRODUCTS SPECIFICATIONS [2247481-21-4]
DESCRIPTION [2247481-21-4]
Overview
| MDL | MFCD31807311 |
|---|---|
| Molecular Weight | 505.08 |
| Molecular Formula | C24H33ClN6O2S |
| SMILES | COCCN[C@@H]1CC[C@@H](NC2=NC=C(Cl)C(C3=CSC(NCC4(C#N)CCOCC4)=N3)=C2)CC1 |
Summary
JSH-150 is a highly selective and potent CDK9 inhibitor with an IC 50 of 1 nM.
IC50 & Target
|
CDK9/cyclinT1 1 nM (IC 50 ) |
CDK16/Cyclin Y 292 nM (IC 50 ) |
Cdk1/cyclin B 1.34 μM (IC 50 ) |
CDK14/Cyclin Y 1.68 μM (IC 50 ) |
CDK7/Cyclin H/MNAT1 1.72 μM (IC 50 ) |
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cdk2/cyclin A 2.86 μM (IC 50 ) |
Cdk5/p25 4.64 μM (IC 50 ) |
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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 GI 50 values from 0.002 to 0.044 µM. 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 GI 50 s ranging from single to double digit nM. In addition, JSH-150 is much less sensitive in normal CHO cells (GI 50 : 1.1 µM) compared with the cancer cell lines [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 (T max =1.33 h and 2.00 h respectively) but slowly in rats (T max =3.33 h). JSH-150 also displays different half-lives in three different species via oral administration (T 1/2 =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 [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 197.99 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9799 mL | 9.8994 mL | 19.7988 mL |
| 5 mM | 0.3960 mL | 1.9799 mL | 3.9598 mL |
| 10 mM | 0.1980 mL | 0.9899 mL | 1.9799 mL |