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MPN Workshop of the Carolinas 2025 | The difference between Type II JAK inhibitors and the clinically approved Type I agents
Andrew Dunbar, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, explains the difference between Type II JAK inhibitors (JAKis) and the clinically approved Type I agents, highlighting the mode of action by which Type II JAKi may offer therapeutic advantages and potentially reduce tumor burden in patients with myeloproliferative neoplasms (MPNs). This interview took place at the 2nd Annual MPN Workshop of the Carolinas, held in Charlotte, NC.
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Transcript
So the main difference between these type II JAK2 inhibitors and all of the other clinically approved agents, which are type I inhibitors, is simply where on the JAK2 protein these compounds are binding. So with the clinically approved agents, these type I inhibitors, they bind JAK2 in an active state. So even though you’re getting downstream signaling inhibition, the JAK2 protein almost remains primed for action, and we think it’s that which contributes to why MPN cells might persist in patients who are receiving these therapies long-term...
So the main difference between these type II JAK2 inhibitors and all of the other clinically approved agents, which are type I inhibitors, is simply where on the JAK2 protein these compounds are binding. So with the clinically approved agents, these type I inhibitors, they bind JAK2 in an active state. So even though you’re getting downstream signaling inhibition, the JAK2 protein almost remains primed for action, and we think it’s that which contributes to why MPN cells might persist in patients who are receiving these therapies long-term. The type II JAK2 inhibitors bind the inactive form of the JAK2 protein. And so we think that by potently suppressing inhibition in this particular setting will, again, not only completely shut off these downstream pathways, but overcome these mechanisms of persistence that, again, not only will prolong treatment response with JAK inhibitors, but also maybe even reduce that MPN tumor burden. So we’ll see.
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Disclosures
Ajax Therapeutics.
