602306-29-6
602306-29-6 structure
- Name: AZD5438
- Chemical Name: 4-(2-methyl-3-propan-2-ylimidazol-4-yl)-N-(4-methylsulfonylphenyl)pyrimidin-2-amine
- CAS Number: 602306-29-6
- Molecular Formula: C18H21N5O2S
- Molecular Weight: 371.457
- Catalog: Biochemical Inhibitor Cell Cycle CDK inhibitor
- Create Date: 2018-12-18 14:14:50
- Modify Date: 2024-01-02 13:36:01
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AZD-5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM in cell-free assays. It also inhibits GSK3β, but is less potent to CDK5/6.
| Name | 4-(2-methyl-3-propan-2-ylimidazol-4-yl)-N-(4-methylsulfonylphenyl)pyrimidin-2-amine |
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| Synonyms |
4-(1-Isopropyl-2-methyl-1H-imidazol-5-yl)-N-[4-(methylsulfonyl)phenyl]pyrimidin-2-amine
AZD 5438 4-(1-Isopropyl-2-methyl-1H-imidazol-5-yl)-N-[4-(methylsulfonyl)phenyl]-2-pyrimidinamine S2621_Selleck 2-Pyrimidinamine, 4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]- AZD-5438,AZD5438 AZD5438 AZD-5438 |
| Description | AZD-5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM in cell-free assays. It also inhibits GSK3β, but is less potent to CDK5/6. |
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| Related Catalog | |
| Target |
cdk2-cyclin E:6 nM (IC50) cdk2-cyclin A:45 nM (IC50) cdk5-p25:14 nM (IC50) cdk1-cyclin B1:16 nM (IC50) cdk9-cyclin T:20 nM (IC50) cdk6-cyclin D3:21 nM (IC50) cdk4-cyclin D1:449 nM (IC50) cdk7-cyclin H:821 nM (IC50) |
| In Vitro | AZD5438 potently inhibits the kinase activity of cyclin E-cdk2, cyclin A-cdk2, cyclin B1-cdk1, p25-cdk5, cyclin D3-cdk6, and cyclin T-cdk9 (IC50, 6, 45, 16, 21, and 20 nM, respectively). AZD5438 potently inhibits the kinase activity of cyclin E-cdk2, cyclin A-cdk2, cyclin B1-cdk1, p25-cdk5, cyclin D3-cdk6, and cyclin T-cdk9 (IC50, 6, 45, 16, 21, and 20 nM, respectively). In common with many other cdk inhibitors, AZD5438 also inhibits the kinase activity of p25-cdk5 and glycogen synthase kinase 3β in vitro (IC50, 14 and 17 nM, respectively)[1]. AZD5438 significantly augments cellular radiosensitivity in NSCLC cells. Combined treatment with AZD5438 and irradiation also enhances tumor growth delay, with an enhancement factor ranging from 1.2-1.7[2]. |
| In Vivo | AZD5438 (50 mg/kg twice daily or 75 mg/kg, p.o.) inhibits human tumor xenograft growth. In vivo, AZD5438 reduces the proportion of actively cycling cells. Further pharmacodynamic analysis of AZD5438-treated SW620 xenografts shows that efficacious doses of AZD5438 (>40% tumor growth inhibition) maintains suppression of biomarkers, such as phospho-pRbSer249/Thr252, for up to 16 hours following a single oral dose[1]. |
| Cell Assay | AZD5438 is tested against solid tumor cell lines as previously described. Briefly, cells are incubated for 48 h with AZD5438 at a range of concentrations. At the end of incubation, the cells are pulsed with 5-bromo-2'-deoxyuridine (BrdUrd) and the amount of DNA synthesis is measured. The IC50 for inhibition of proliferation is specifically determined independently of cell death. Multiple myeloma cell lines are seeded into 96-well plates in RPMI 1640 supplemented with 10% FCS and glutamine and dosed with AZD5438 for 72 h. Cell growth is measured using AlamarBlue and GI50 values are calculated with reference to pretreatment control values. |
| Animal Admin | All human tumor xenografts except HX147 are established by s.c. injecting 100 μL of tumor cells (between 1×106 and 1×107 cells mixed 1:1 with Matrigel). HX147 tumors are derived from fragment implants (1 mm3 pieces) from tumors taken from mice initially implanted s.c. with 1×107 cells. These tumor fragments are passaged in mice thrice before implant for antitumor work. Tumors are measured up to three times per week with calipers, tumor volumes are calculated, and the data are plotted as geometric mean for each group versus time, as previously described. Animals are randomized into treatment groups (typically n=10) when tumors reach a mean size of approximately >0.2 cm3 and >0.5 cm3 for mice and rats, respectively. AZD5438 is prepared in hydroxy-propyl-methyl-cellulose. Animals are given either AZD5438 (37.5-75 mg/kg) or vehicle control once or twice daily by oral gavage for appr 3 wk in each case. Tumor volume and percentage tumor growth inhibition (% TGI) are calculated as described previously. Statistical analysis of any change in tumor volume is carried out using a standard t test (P<0.05 is considered to be statistically significant). |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 655.2±65.0 °C at 760 mmHg |
| Molecular Formula | C18H21N5O2S |
| Molecular Weight | 371.457 |
| Flash Point | 350.1±34.3 °C |
| Exact Mass | 371.141602 |
| PSA | 98.15000 |
| LogP | 2.13 |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C |
| Index of Refraction | 1.648 |
| Storage condition | Desiccate at RT |
| HS Code | 2933990090 |
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| HS Code | 2933990090 |
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| Summary | 2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0% |