🔥The 9th Round of Easy Loan, Earn $40 Reward is in progress❗️ ⏰ Promotion Period: January 15th - Feburary 15th, 2025 👉 Register now and check more details at gate.io/campaigns/358

Today we’re launching The Tahoe Blog from Tahoe Therapeutics (Formerly Vevo). In the same open-source spirit that led us to release Tahoe-100M—our gigascale, perturbative single-cell dataset—we’re now sharing many of the discoveries it has enabled. 🧬✨ Link to the Blog and the inaugural post in 🧵

Check out today's post where we show that an HIV antiviral🧬, Saquinavir, developed by Roche actually activates the b-adrenergic pathway more like Norepinephrine! Would you want to take something given after acute cardiac arrest daily to treat HIV? Big data -> discoveries 👇

Follow the Tahoe Blog to stay up to date with our latest findings blog.tahoebio.ai 🚀 #buildingopenly

1/ 🧵 THREAD: Here’s how we solved a 30-year mystery about an HIV drug. 💊 A drug used for over two decades ⚠️ Pulled from the market for cardiac risk 🤯 And no one knew why — until now We found the missing mechanism using our single-cell mosaic dataset, Tahoe-100M. Let’s talk

2/ This all started with Tahoe-100M—a massive single-cell dataset profiling ~400 drugs across human cell states. We asked: Can transcriptional signatures reveal off-target effects and mechanisms of action no one else can see? Absolutely.

3/ 🧪 Saquinavir, some quick facts: -Developed by Roche -HIV protease inhibitor -FDA-approved in 1995 -Used in patients for decades -Later pulled due to ⚠️ QT prolongation + arrhythmias (cardiac toxicity) FDA flagged the safety risk, and Roche pulled the drug from market. But

4/ We compared Saquinavir’s transcriptional profile against every other drug in our dataset. Surprisingly - what ranked the highest was: ✅ Norepinephrine ✅ Vilanterol = Classic adrenoceptor agonists Despite zero chemical resemblance!

5/ Adrenoceptor agonists ramp up: 📈 cAMP 📈 pCREB 🫀 Blood pressure So we ran a pCREB western blot after Saquinavir treatment to validate if the biology was similar. Saquinavir lit up exactly like Norepinephrine.

6/ Why does this matter? Norepinephrine is used to raise blood pressure. Saquinavir wasn’t designed to affect the heart at all. But it mimics adrenergic activation. This is likely the real reason for its long-known cardiotoxicity that took clinicians two decades of trial and

7/ Even the FDA flagged cardiac risk: ⚠️ QT prolongation ⚠️ Arrhythmia But cited no mechanistic basis. Our discovery connects the dots — not via ion channels, but via transcriptional mimicry of adrenoceptor agonism. 📜

8/ Here’s the kicker: 🧠 Saquinavir, Vilanterol, and Norepinephrine have very different structures... …but converge on the same biological effect. It's only through this type of new data modality in Tahoe100M where we could see this biological similarity!

9/ We didn’t design this experiment to investigate Saquinavir. We just included it in our 400-drug map. And thanks to the resolution of Tahoe-100M, the transcriptional MoA was instantly obvious. This is the new playbook for safety + repurposing.

10/ Imagine what else is hiding in the pipeline today. Drugs headed for market with mechanisms we think we know... Until single-cell data shows otherwise. 🧬 Tahoe-100M lets you: – Infer MoA fast – Detect off-targets – Repurpose smarter – De-risk development

11/ Read the full story on our blog 👇 🔗 blog.tahoebio.ai/p/saquinavir-u… And if you’re building or studying drugs with unknown effects — or want to use Tahoe-100M — get in touch: 📬 [email protected] 📥 DMs open Follow us Tahoe Therapeutics (Formerly Vevo) for more. #drugdiscovery #singlecell #pharma

We're getting ready to kick-off the Hackathon Weekend 🚀 #TahoeDeepDive

Hugging Face 🤝 Tahoe Therapeutics Hackathon now in full swing! Looking forward to some cool projects!

Late night hackathon project planning #TahoeDeepDive

💙

#TahoeDeepDive 💙

On a personal level, it's special to see a dataset go from an idea -> an experiment -> a community like this. What a smart and curious group of people at the leading edge of the Virtual Cell! This will definitely be a moment in time.