AST-487 / Novartis - LARVOL DELTA

Convergent genome evolution shaped the emergence of terrestrial animals. (PubMed, Nature) - "Our timeline supports three temporal windows of land colonization by animals during the last 487 million years, each associated with specific ecological contexts. Although each lineage exhibits distinct adaptations, there is strong evidence of convergent genome evolution across the animal kingdom suggesting that, in large part, adaptation to life on land is predictable, linking genes to ecosystems."

Journal • Preclinical

AST-487 Inhibits RET Kinase Driven TERT Expression in Bladder Cancer. (PubMed, Int J Mol Sci) - "We also identified the RET kinase pathway, targeted by AST-487, as a novel regulator of mutant hTERT promoter-driven transcription in bladder cancer cells. Collectively, our work provides new potential precision medicine approaches for cancer patients with upregulated hTERT expression, perhaps, especially those harboring mutations in both the RET gene and the hTERT promoter, such as in thyroid cancer."

Journal • Bladder Cancer • Brain Cancer • Endocrine Cancer • Genito-urinary Cancer • Glioblastoma • Melanoma • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Urothelial Cancer • RET • TERT

Inhibition of HIPK3 by AST487 Ameliorates Mutant HTT-Induced Neurotoxicity and Apoptosis via Enhanced Autophagy. (PubMed, Neurosci Bull) - No abstract available

Journal

Involvement of the CDKL5-SOX9 signaling axis in rhabdomyolysis-associated acute kidney injury. (PubMed, Am J Physiol Renal Physiol) - "In addition, a small molecule kinase inhibitor AST-487 alleviated rhabdomyolysis-associated AKI in a Cdkl5-dependent manner...Based on these studies we propose that by suppressing the protective Sox9-directed transcriptional program, Cdkl5 contributes to rhabdomyolysis-associated renal impairment. Together, these studies have identified Cdkl5 as a critical stress-induced kinase that drives RTEC dysfunction and kidney injury linked with distinct etiologies."

Journal • Acute Kidney Injury • Cardiovascular • Infectious Disease • Nephrology • Renal Disease • Septic Shock • SOX9