tak-441 has been researched along with Medulloblastoma* in 2 studies
1 review(s) available for tak-441 and Medulloblastoma
| Article | Year |
|---|---|
Medulloblastoma drugs in development: Current leads, trials and drawbacks.
Medulloblastoma (MB) is the most common malignant brain tumor in children. Current treatment for MB includes surgical resection, radiotherapy and chemotherapy. Despite significant progress in its management, a portion of children relapse and tumor recurrence carries a poor prognosis. Based on their molecular and clinical characteristics, MB patients are clinically classified into four groups: Wnt, Hh, Group 3, and Group 4. With our increased understanding of relevant molecular pathways disrupted in MB, the development of targeted therapies for MB has also increased. Targeted drugs have shown unique privileges over traditional cytotoxic therapies in balancing efficacy and toxicity, with many of them approved and widely used clinically. The aim of this review is to present the recent progress on targeted chemotherapies for the treatment of all classes of MB. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cerebellar Neoplasms; Humans; Medulloblastoma; Protein Kinase Inhibitors | 2021 |
1 other study(ies) available for tak-441 and Medulloblastoma
| Article | Year |
|---|---|
Discovery of the investigational drug TAK-441, a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: modification of the core skeleton for improved solubility.
We recently reported the discovery of the novel pyrrolo[3,2-c]quinoline-4-one derivative 1 as a potent inhibitor of Hedgehog (Hh) pathway signaling. However, the PK evaluation of 1 at high dosage (100 mg/kg) revealed the C(max) value 3.63 μg/mL, likely due to poor solubility of this compound. Efforts to improve solubility by reducing the aromatic ring count of the core system led to N-methylpyrrolo[3,2-c]pyridine derivative 11. Further optimization of the 3-alkoxy group led to compound 11d with acceptable solubility and potent Hh inhibitory activity. Compound 11d suppressed transcription factor Gli1 mRNA expression in tumor-associated stromal tissue and inhibited tumor growth (treatment/control ratio, 3%) in a mouse medulloblastoma allograft model owing to the improved PK profile based on increased solubility. Compound 11d (TAK-441) is currently in clinical trials for the treatment of advanced solid tumors. Topics: Animals; Antineoplastic Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Discovery; Hedgehog Proteins; Humans; Kruppel-Like Transcription Factors; Medulloblastoma; Mice; Mice, Nude; Models, Molecular; Molecular Structure; NIH 3T3 Cells; Pyridines; Pyrroles; RNA, Messenger; Signal Transduction; Solubility; Structure-Activity Relationship; Transplantation, Homologous; Zinc Finger Protein GLI1 | 2012 |