602306-29-6

Basic information

• Product Name: AZD 5438
• Synonyms: 2-Pyrimidinamine,4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-;AZD 5438;2-Pyrimidinamine,4-[2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-(AZD 5438);4-[2-Methyl-1-isopropyl-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-2-pyrimidinamine;4-[2-Methyl-1-(1-methylethyl)-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-2-pyrimidinamine;AZD;4-[2-Methyl-1-(1-Methylethyl)-1H-iMidazol-5-yl]-N-[4-(Methylsulfonyl)phenyl]-;4-[2-Methyl-1-isopropyl-1H-imidazol-5-yl]-N-[4-(methylsulfonyl)phenyl]-2-pyrimidinamine AZD 5438
• CAS NO: 602306-29-6
• Molecular Formula: C18H21N5O2S
• Molecular Weight: 371.46
• Product Categories: API intermediates;Potent inhibitor of cyclin-dependent kinase (cdk) 1, 2 and 9.;Inhibitors
• Mol File: 602306-29-6.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 655.2 °C at 760 mmHg
• Flash Point: 350.1 °C
• Appearance: /
• Density: 1.31
• Vapor Pressure: 4.79E-17mmHg at 25°C
• Refractive Index: 1.647
• Storage Temp.: Desiccate at RT
• Solubility: insoluble in H2O; ≥18.55 mg/mL in DMSO; ≥42.1 mg/mL in EtOH
• PKA: 4.08±0.50(Predicted)
• CAS DataBase Reference: AZD 5438(CAS DataBase Reference)
• NIST Chemistry Reference: AZD 5438(602306-29-6)
• EPA Substance Registry System: AZD 5438(602306-29-6)

Safety Data

• Hazardous Substances Data: 602306-29-6(Hazardous Substances Data)

Usage

Description

AZD 5438 is a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, which are key regulators of cell cycle progression and transcription. By inhibiting these kinases, AZD 5438 can lead to pharmacodynamic changes and potent antitumor effects in human tumor xenografts, making it a promising candidate for cancer treatment.

Uses

Used in Oncology:
AZD 5438 is used as an anticancer agent for its ability to inhibit cyclin-dependent kinases 1, 2, and 9, which play crucial roles in cell cycle regulation and transcription. This inhibition results in pharmacodynamic changes and potent antitumor effects in human tumor xenografts, making it a valuable compound in the fight against cancer.
Used in Drug Development:
AZD 5438 is used as a research tool in the development of new cancer therapies. Its potent inhibition of cyclin-dependent kinases 1, 2, and 9 provides a foundation for understanding the effects of these kinases on cancer cell growth and proliferation. This knowledge can be applied to the design of more effective and targeted cancer treatments.
Used in Preclinical Research:
AZD 5438 is used in preclinical research to study the effects of inhibiting cyclin-dependent kinases 1, 2, and 9 on tumor growth and progression. This research helps to determine the potential efficacy and safety of AZD 5438 as a cancer treatment, as well as its potential for combination therapies with other anticancer agents.

Biological Activity

azd5438 is a potent small molecule inhibitor of cyclin-dependent kinase (cdk) 1, 2 and 9 with half maximal inhibitory concentration ic50 of 16 nmol/l, 6 nmol/l and 20 nmol/l respectively. azd5438 has also been found to potently inhibit the human cyclin e/cdk2 complex, the cyclin b1/cdk1 complex and the cyclin a/cdk2 complex with ic50 of 0.006 μm, 0.016 μm and 0.045 μm respectively. in previous studies, azd5438 has exhibited significant anti-proliferative activity in a few human tumor cell lines with ic50 ranging from 0.2 μmol/l to 1.7 μmol/l, in which the phosphorylation of a few proteins, including cdk substrates prb, nucleolin, protein phosphatase 1a and rna polymerase ii cooh-terminal domain, and cell cycling at g2-m, s and g1 phases were inhibited.

references

[1]camidge dr1, smethurst d, growcott j, barrass nc, foster jr, febbraro s, swaisland h, hughes a. a first-in-man phase i tolerability and pharmacokinetic study of the cyclin-dependent kinase-inhibitor azd5438 in healthy male volunteers. cancer chemother pharmacol. 2007 aug;60(3):391-8. epub 2006 nov 18.[2]byth kf, thomas a, hughes g, forder c, mcgregor a, geh c, oakes s, green c, walker m, newcombe n, green s, growcott j, barker a, wilkinson rw. azd5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. mol cancer ther. 2009 jul;8(7):1856-66. doi: 10.1158/1535-7163.mct-08-0836. epub 2009 jun 9.

InChI:InChI=1/C18H21N5O2S/c1-12(2)23-13(3)20-11-17(23)16-9-10-19-18(22-16)21-14-5-7-15(8-6-14)26(4,24)25/h5-12H,1-4H3,(H,19,21,22)

Relevant articles and documents

Restricted suitability of BODIPY for caging in biological applications based on singlet oxygen generation

Recent studies report the boron-dipyrromethene (BODIPY) moiety to be interesting for caging applications in photopharmacology based on its response to irradiation with wavelengths in the biooptical window. Thus, in a model study, we investigated the meso-methyl-BODIPY caged CDK2 inhibitor AZD5438 and aimed to assess the usability of BODIPY as a photoremovable protecting group in photoresponsive kinase inhibitor applications. Photochemical analysis and biological characterisation in vitro revealed significant limitations of the BODIPY-caged inhibitor concept regarding solubility and uncaging in aqueous solution. Notably, we provide evidence for BODIPY-caged compounds generating singlet oxygen/radicals upon irradiation, followed by photodegradation of the caged compound system. Consequently, instead of caging, a non-specific induction of necrosis in cells suggests the potential usage of BODIPY derivatives for photodynamic approaches.