bay-1000394 and Uterine-Cervical-Neoplasms

bay-1000394 has been researched along with Uterine-Cervical-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for bay-1000394 and Uterine-Cervical-Neoplasms

Article	Year
The lab oddity prevails: discovery of pan-CDK inhibitor (R)-S-cyclopropyl-S-(4-{[4-{[(1R,2R)-2-hydroxy-1-methylpropyl]oxy}-5-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)sulfoximide (BAY 1000394) for the treatment of cancer. ChemMedChem, 2013, Volume: 8, Issue:7 Lead optimization of a high-throughput screening hit led to the rapid identification of aminopyrimidine ZK 304709, a multitargeted CDK and VEGF-R inhibitor that displayed a promising preclinical profile. Nevertheless, ZK 304709 failed in phase I studies due to dose-limited absorption and high inter-patient variability, which was attributed to limited aqueous solubility and off-target activity against carbonic anhydrases. Further lead optimization efforts to address the off-target activity profile finally resulted in the introduction of a sulfoximine group, which is still a rather unusual approach in medicinal chemistry. However, the sulfoximine series of compounds quickly revealed very interesting properties, culminating in the identification of the nanomolar pan-CDK inhibitor BAY 1000394, which is currently being investigated in phase I clinical trials. Topics: Animals; Antineoplastic Agents; Cyclin-Dependent Kinases; Dose-Response Relationship, Drug; Drug Discovery; Female; HeLa Cells; High-Throughput Screening Assays; Humans; Mice; Models, Molecular; Molecular Structure; Molecular Weight; Neoplasms, Experimental; Protein Kinase Inhibitors; Pyrimidines; Rats; Structure-Activity Relationship; Sulfoxides; Uterine Cervical Neoplasms	2013

Article

Year

The lab oddity prevails: discovery of pan-CDK inhibitor (R)-S-cyclopropyl-S-(4-{[4-{[(1R,2R)-2-hydroxy-1-methylpropyl]oxy}-5-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)sulfoximide (BAY 1000394) for the treatment of cancer.

ChemMedChem, 2013, Volume: 8, Issue:7

Lead optimization of a high-throughput screening hit led to the rapid identification of aminopyrimidine ZK 304709, a multitargeted CDK and VEGF-R inhibitor that displayed a promising preclinical profile. Nevertheless, ZK 304709 failed in phase I studies due to dose-limited absorption and high inter-patient variability, which was attributed to limited aqueous solubility and off-target activity against carbonic anhydrases. Further lead optimization efforts to address the off-target activity profile finally resulted in the introduction of a sulfoximine group, which is still a rather unusual approach in medicinal chemistry. However, the sulfoximine series of compounds quickly revealed very interesting properties, culminating in the identification of the nanomolar pan-CDK inhibitor BAY 1000394, which is currently being investigated in phase I clinical trials.

Topics: Animals; Antineoplastic Agents; Cyclin-Dependent Kinases; Dose-Response Relationship, Drug; Drug Discovery; Female; HeLa Cells; High-Throughput Screening Assays; Humans; Mice; Models, Molecular; Molecular Structure; Molecular Weight; Neoplasms, Experimental; Protein Kinase Inhibitors; Pyrimidines; Rats; Structure-Activity Relationship; Sulfoxides; Uterine Cervical Neoplasms

2013