Josh Coats
@joshcoats
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Lymphoma | Science-based medicine | Haematologist @NHSTayside | Hon Clin Lecturer @UoDMedicine
Dundee, Scotland
Joined April 2008
Our latest work on elraglusib is now out in preprint - with some new mechanistic insights. Huge thanks to @AdeSaurin and the whole Saurin lab for all their help.
I know it's important to move new drugs into cancer trials as quickly as possible, but we also need to carefully study how these drugs actually work. Otherwise, we'll end up firing shots in the dark.... Read our latest work on a "GSK3 inhibitor" here: https://t.co/9GR442jgT3
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Exciting news in UK lymphoma Glofit+GemOx approved for 2L use in #DLBCL in the UK by @NICEComms #lymsm
https://t.co/JLGfDE6sNq
bloodcancer.org.uk
People living with diffuse large B-cell lymphoma (DLBCL), an aggressive type of blood cancer, who don’t respond to treatment or whose cancer has come back, will soon have access to a new treatment on...
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Great news for people with blood cancer in Scotland! 🎉 The Scottish Medicines Consortium has now approved two blood cancer treatments, which are already available in England. 1/3
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Our latest work shows a reported #kinase inhibitor causes cytotoxicity by directly inhibiting MTs. We need more clarity on how #chemotherapy drugs work if we are to use them effectively to treat #cancer. Work led by fantastic clinical fellow @joshcoats
aacrjournals.org
Abstract. Elraglusib (9-ING-41) is an ATP-competitive inhibitor of glycogen synthase kinase-3 (GSK3) with preclinical studies demonstrating broad activity against many tumor types. Promising early-...
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the practice changing STARGLO phase 3 trial demonstrating OS superiority for glofitamab-GemOx over R-GemOx in r/r DLBCL published today in @TheLancet erudite commentary from @AnnaSureda5
@AstridPavlovsky
#lymSMfree access via this link: https://t.co/xbSuG2B7FF
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Our #ASH23 abstract builds on our previous work on elraglusib (9-ING-41) & GSK3 in lymphoma. We show that significant genetic depletion of GSK3a & GSK3b does not affect elraglusib sensitivity thereby further questioning GSK3 as its cytotoxic target. https://t.co/gFXbmPhdVo
ashpublications.org
Disclosures. No relevant conflicts of interest to declare.Figure 1
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#ASH23 Harada et al intravascular large B-cell lymphoma 1 of 2 settings in which I still use high-dose methotrexate as CNS prophylaxis! retrospective analysis n=110, but a rare disease and convincing treatment effect #lymSM
https://t.co/6mDitzhQis
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Among study participants with lymphoma who were being treated with anthracyclines, prophylactic use of atorvastatin over 12 months was associated with a lower rate of cardiac systolic dysfunction. https://t.co/JZVqaltrYA
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Recent work by @joshcoats at Calum Sutherland lab clearly shows that the anti-lymphoma activity of Phase 2 drug Elraglusib (ING-9-41) cannot solely be attributed to GSK3 inhibition. @UoDMedicine @BioMedCentral
https://t.co/8f6KfXzmTk
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Taken together we have reaffirmed that elraglusib has significant anti-lymphoma effects but argue that these effects cannot be attributed to its effects on GSK3. The definitive mechanism of action of elraglusib is yet to be confirmed.
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Cell-free kinase assays confirmed that elraglusib has a significantly higher IC50 than the other inhibitors and identified significant off-target effects on other kinases (see paper) which may be contributing to its mechanism of action.
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Analysis of GSK3 substrates (CRMP2 and β-catenin) in cell lysates found only weak evidence of GSK3 inhibition by elraglusib (at 4 hours).
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Elraglusib was also the only inhibitor which induced apoptosis (following 24 hour exposure).
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Only elraglusib significantly reduced cell viability (at 72 hours). This effect was not shared by CT99021, SB216763, LY2090314 or Tideglusib.
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We investigated elraglusib and several other structurally unrelated GSK3 inhibitors (CT99021, SB216763, LY2090314 and tideglusib) in diverse lymphoma cell lines (1x B-cell and 2x T-cell).
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Elraglusib (developed by @ActuateT) is a GSK3 inhibitor found to be active in lymphoma by Karmali et al (@NUFeinbergMed) and @xwux et al (@WitzigLab @MayoClinic) and now in clinical trials for various cancers.
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Our paper on elraglusib (9-ING-41) in lymphoma has just been published @BioMedCentral : Elraglusib (formerly 9-ING-41) possesses potent anti-lymphoma properties which cannot be attributed to GSK3 inhibition https://t.co/0no2K2dSTC
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5th edition of WHO classification of hematolymphoid tumors (both myeloid and lymphoid) is out @LeukemiaJnl Congrats to the entire team! https://t.co/5gMNonM5jK
https://t.co/dEHtCb2g9a
nature.com
Leukemia - The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms
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Why do people with cholestasis itch? The short answer is we don’t fully know. The long answer is much more interesting. Last weekend before Cards Fellowship writing my first tweetorial. Here we go! (photo by Gustave Doré)
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