Gifts from my dad. The left book is from '96 and the right from '93. I feel like there's a winter's project in flipping through these and noting how much has changed in 30 years.
Anthony Barente
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Bioinformaticist interested in #Proteomics, #Genomics, and #DataScience. Currently building software for #SyntheticBiology at Ginkgo Bioworks.
One missense variant in particular is notable. R479H is the most common variant causing pyruvate kinase deficiency in Amish individuals.
While the substitution was included in the original Mitapivat (aka AG-348) publication, the main effect of the variant is thought to come from disrupted splicing instead. Individuals with the variant showed no benefit in phase 2 and were not included in phase 3.
Figure citations:
a) https://pubmed.ncbi.nlm.nih.gov/28760888/
b) Splicing hypothesis from https://pubmed.ncbi.nlm.nih.gov/11960989/
AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency - PubMed
Pyruvate kinase (PK) deficiency is a rare genetic disease that causes chronic hemolytic anemia. There are currently no targeted therapies for PK deficiency. Here, we describe the identification and characterization of AG-348, an allosteric activator of PK that is currently in clinical trials for the …
Came across an interesting drug the other day, Mitapivat.
It's target is the red blood cell isoform of pyruvate kinase (PKLR) whose loss of function is a common cause of a form of hereditary hemolytic anemia.
Mitapivat is thought to increase the affinity of missense variants of this enzyme to phosphoenolpyruvate (PEP) and a phase 3 study showed that 40% of the treatment group experienced a increase of hemoglobin levels.
Figure citations:
a) https://pubmed.ncbi.nlm.nih.gov/28760888/
b) https://pubmed.ncbi.nlm.nih.gov/35417638/
AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency - PubMed
Pyruvate kinase (PK) deficiency is a rare genetic disease that causes chronic hemolytic anemia. There are currently no targeted therapies for PK deficiency. Here, we describe the identification and characterization of AG-348, an allosteric activator of PK that is currently in clinical trials for the …