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sebetralstat

Context. Sebetralstat (KalVista Pharmaceuticals) is an oral, on-demand plasma kallikrein (PKa) inhibitor intended for hereditary angioedema (HAE). As an on-demand medication, it can be administered to treat acute attacks rather than chronically to prevent attacks. Its structure was first disclosed at the ACS Spring Meeting earlier this year. HAE is a rare autosomal dominant disease…

GDC-2394

Context. GDC-2394 (Genentech) is an oral NLRP3 inflammasome inhibitor. The NLRP3 inflammasome is the best studied and most characterized inflammasome, with the protein playing a key role in the detection of inflammatory danger signals which are a hallmark of many inflammatory diseases. Hyperactivation of the NLRP3 has been implicated in the pathogenesis of several diseases…

compound 5g

Context. “Compound 5g” (Incyte) is a selective CDK2 kinase inhibitor. Although CDK2 is a highly pursued cancer drug target, inhibitors targeting the key cell cycle regulator have not enjoyed similar success as CDK4/6 inhibitors, in part due to the major challenge of mitigating off-target CDK1/9 activity through the use of highly selective agents. Given recent…

AZD1656

Context. AZD1656 (AstraZeneca)is an oral glucokinase (GK) activator (GKA) for hyperglycemia in type 2 diabetes mellitus. Despite GK being first reported more than 50 years ago and subsequent extensive research efforts, a GKA is yet to be approved. Most GKAs have failed in clinical development owing to an increased risk of hypoglycemia and gradual loss…

JNJ-64264681

Context. JNJ-64264681 (Janssen) is a covalent Bruton’s tyrosine kinase (BTK) inhibitor being developed for hematological malignancies. The first-in-class irreversible BTKi (ibrutinib) was approved in 2013, while many others have been approved or are in clinical development with potentially reduced off-target effects. We recently covered another covalent BTKi, rilzabrutinib, (PRN1008; Sanofi), currently in Ph. III for…

BI-0474

Context. BI-0474 (Boehringer Ingelheim) is a covalent KRASG12C inhibitor. KRAS continues to be a hotly pursued oncotarget since the first report by the Shokat group of the druggability of the KRASG12C mutant. Recently, Amgen’s first-in-class sotorasib (Lumakras) was approved, while Mirati Therapeutics’ adagrasib (MRTX84) may be approved in December 2022, based on its PDUFA date.…