Jay Bradner, M.D.

All in the Simi Valley area and neighboring communities, please take note of this new Sandy Fire and wind patterns. Stay safe and take best care.

ICYMI. Singer and guitarist @ericchurch at UNC Commencement. Reflective, touching, deeply affecting. Will be watching this again with Jennifer and the kids.

Parked right next to it at the Waxahatchee & MJ Lenderman show last evening in LA. IYKYK, respect the total commitment. Incredible performance by @MarkJLenderman @k_crutchfield @waxa_katie

@wgibson @TaaviNeklesa Thanks for the quick and kind note. Wish I could be that guy but tied up with therapeutics. The GOAT of Kac proteomics is Prof. Chuna Choudhary at Univ Copenhagen. But can always IP-IB try using a polyclonal Kac mAb. Great paper, Will!

Unsurprisingly, these are the exact right questions Jay. There’s a lot to be learned about RIPTACs here.. (and I’m still scratching my head that they work and how). I’ve found @TaaviNeklesa to be a great thought partner in this area. We’ve been wanting to look at acetylation, but haven’t found a good mass spec partner to help with this quite yet. More to learn as always!

Very nice study by @wgibson, on bifunctionals in gene control. The EWS-FLI1 signature impact of the JQ1-based recruiter is nice. Worth studying the AR-binding JQ1 ligands from Halda/JNJ, in this way. Contribution of RIPTAC and TCIP components would be very interesting. (Also curious if the potent aTAG-2 acetylates EWS-FLI1 or the chimeric FKBP12). Great read, Will!

What if a small molecule could activate a transcription factor program in one cell type and destroy the same pathway in another? In our new preprint, we describe one such story on bifunctional molecules that toggle between transactivation and repression.

Telomeres are longer on the West Coast. Been in SoCal for only eight months and can already feel it. Nice GWAS on leukocyte telomere length and genetic associations in @NatureGenet by @pnatarajanmd and colleagues. nature.com/articles/s4158…

@bherzbergmd @CentralParkWMD @NEJM @CpcrMsk @MSK_DeptOfMed @PanCAN @letswinpc @lustgartenfdn @CD_AACR @NatPancFdn @anup_kasi @MeredithPelster @jordanberlin5 @HollebecqueA @do_phd @MacarullaTeresa Anything for @columbiacancer and the @bherzbergmd lab!

@jaybradner @CentralParkWMD @NEJM @CpcrMsk @MSK_DeptOfMed @PanCAN @letswinpc @lustgartenfdn @CD_AACR @NatPancFdn @anup_kasi @MeredithPelster @jordanberlin5 @HollebecqueA @do_phd @MacarullaTeresa Jay can we throw you on the translational team?

1/n Setidegrasib the first-in-human, first-in-class, KRAS G12D-targeted protein degrader #TPD Our KRAS G12D degrader study is now published in the New England Journal of Medicine @NEJM nejm.org/doi/full/10.10… A new way to target KRAS G12D - one of the most common oncogenic drivers across cancers.

@CentralParkWMD @NEJM @CpcrMsk @MSK_DeptOfMed @PanCAN @letswinpc @lustgartenfdn @CD_AACR @NatPancFdn @anup_kasi @bherzbergmd @MeredithPelster @jordanberlin5 @HollebecqueA @do_phd @MacarullaTeresa Very interesting. Would have expected a mutant selective degrader to be much better tolerated. Infusion reactions are uncommon for targeted therapies. Is the VHL engaging feature a challenge? Perhaps a peptidyl feature or solubilizing excipient is provoking an immune reaction?

@NEJM @CpcrMsk @MSK_DeptOfMed @PanCAN @letswinpc @lustgartenfdn @CD_AACR @NatPancFdn 8/ Grateful to the patients, global collaborators and the incredible external and internal collaborators. @anup_kasi @bherzbergmd @MeredithPelster @jordanberlin5 @HollebecqueA @do_phd @MacarullaTeresa and many others who are not on X. More to come. Stay tuned!

Learned today of the passing of Phil Low, a drug hunter, scholar, educator and just lovely man. His work to target cancer cells via folic acid receptors, among so many other creative ideas, were a source of inspiration so many years ago. It was an honor to work with him on PSMA radioligand therapy, and to develop his inventions further to real medicines while at Novartis. Phil was a dynamo in his Purdue laboratory, surrounded by adoring trainees, at a whiteboard or pounding through 80 packed Powerpoint slides in 30 breathless minutes. I am glad and better to have known you, Phil. Your memory is a blessing. linkedin.com/posts/purdue-u…

Happy Birthday, Ty! Good boy. Have some cheese.

Mitochondria and Chloroplasts set aside their differences (cellular respiration vs photosynthesis, oxygen vs light, christae vs thylakoids) @GordonConf this July. @VamsiMootha accepting abstracts and terminal electrons now.

@ideapharma Congratulations on a legacy of ideas, influence and impact. After a well deserved guitar solo, do continue to inspire on this and other channels. We are all tuned in.

After 25 of the best possible years, today was my last day at IDEA Pharma I wish my friends there, the best team I have ever worked with, the greatest success as they continue to change the industry for the better. I'll always be the company's biggest fan. I hope I've made some difference to one of the most important industries, and I don't think I'm done yet. I'm going to take some time with Clare, finish a couple of books that I have in draft, and remind myself why I have so many guitars… Thank you to everyone at IDEA. You've surrounded me with the biggest hearts and brains for a long time, and I've loved almost every minute. To Alexander Gray in particular, my smarter and better half, thank you for everything 🙏🏻

Had the pleasure of joining fellow biotech leaders at the #LongwoodHealthcareLeaders #SanFranciscoCEO meeting for a candid discussion on where R&D is headed — and how our industry must continue to evolve to meet unmet patient needs and deliver meaningful innovation. Thank you to @LongwoodLeaders and @LongwoodFund for convening such a thoughtful group and for the opportunity to share how @Amgen is designing the medicines of tomorrow.

@rosslevinemd Thank you Ross @rosslevinemd. Your work has discovered so many actionable targets in myeloid malignancies. AML quite urgently needs more therapeutic development. Proud to work alongside the Dark Blue innovators!

Thanks Bruce @LifeSciVC. Time cannot move fast enough to bring this brave idea and prototype medicine to patients with AML. As a stem cell transplant physician, I am well calibrated to the challenge AML patients face. All learnings, insights and leaders at @Amgen in ALL will be accessible to this amazing team of innovators.

Stunning use of dTAG to study rapid dynamics of chromatin structure and cis-regulatory interactions at high resolution. Blueprint for studying mechanistic effects of TF degraders / modulators.

@immasiddx @karpathy You have very nice handwriting.

Google’s Nano Banana Pro is by far the best image generation AI out there. I gave it a picture of a question and it solved it correctly in my actual handwriting. Students are going to love this. 😂