Kevin A. Scott
@sculpturatus
Director of Discovery Chemistry at Stealth Medicines www.sculpturatus.com Evolution-Guided Pharmacology, Drug Discovery, Chemical Immunology, Aging
the whitehouse just removed 7 vaccines from the childhood recommendation list. here's who manufactures them.
the back half of 2026 is stacked for FDA decisions 👀 a new mechanism for hypertension (lorundrostat), maybe the first BTK inhibitor for primary CNS lymphoma (tirabrutinib), and a sodium-current drug for rare pediatric epilepsies (relutrigine) i'm really pulling for. good time to be in this field
one thing we don’t think about enough with covalent drugs is hapten-mediated immunogenicity. if your drug can covalently modify proteins, some of those modified peptides can end up on MHC and look like completely new antigens to the immune system. covalency creates some pretty unique liabilities.
urushiol is the poison in poison oak. it covalently modifies proteins which get displayed on MHC and lead to a T cell autoimmune response. wild.
Viagra has an off target effect on PDE6, an enzyme in the eye involved in phototransduction. This leads to blue tinted vision. Pfizer then patented the blue pill and made their commercials blue.
why do like 99% of structures for lactose online include 2 extra carbons in the linkage? this is grossly incorrect.
why do so many websites have the wrong structure for HATU #chemsky
Chirality abounds! And we're on track to a solid year of small molecule approvals with several first in class drugs to be excited about.
A subset of CysDB fragments occupies chemical space with no overlap with approved drugs — likely flat, aromatic, low-complexity chemotypes underrepresented in drug space. The overlapping subset probes cysteine sites with drug-like physicochemistry. sculpturatus.com/surveyorchemscape
Check out my post a couple minutes ago. S stereocenters used to be 67% in 1960 and it's been declining ever since we moved away from amino acids for chiral centers. Feel free to use these or let me know if you have a specific interest. Happy to share the structural data if you want to analyze
In 1960, 67% of stereocenters in FDA drugs were S. By 2025: 53%. A 65-year erasure of biosynthetic bias by synthetic chemistry — written in R and S. (n=1,212 drugs, RDKit)
Half of FDA-approved drugs are achiral. Of the chiral half, R/S splits 53/47 favoring S — statistically real, but barely. Natural product biosynthetic bias, slowly erased by synthetic chemistry. (n=1,217, RDKit)
eplore the chemical space of drugs for free with zero coding using Surveyor Chemscape. just point, click, and analyze. sculpturatus.com/chemscape/
thia-aza-bicyclooctenone is my new favorite heterocycle. see the full synthesis here. chemistrybydesign.oia.arizona.edu/app/#Sword%2...
Surveyor Chemscape is now available as a webapp. you can begin by uploading your own CSV molecule datasets or by using the available ones (click compute projection). play around, have fun, let me know if you want new datasets. sculpturatus.com/chemscape
Want to compare your molecules to FDA-approved drugs or the Enamine 10k library? I made an open-source tool that visualizes physicochemical properties and metrics like Böttcher complexity as 2D/3D PCA or UMAP plots. Fast and easy. Mac only. github.com/sculpturatus...
the number of clinical trials we would have to do to achieve that goal vastly exceeds the number of patients eligible for those trials
there's a Rapamycin Renaissance going on with over 15 current clinical trials
one of the reasons i like to photograph reflections in water is because they offer the enantiomers of every day chiral objects.
alphafold uses covariation in evolutionary sequence alignments to predict structural contacts. evolution-guided pharmacology uses covariation networks to identify functional hotspots — evolutionarily constrained regions that may be pharmacologically targetable. more soon.
most “world-changing equations” aren’t independent of one another. rather, they’re different views of the same underlying math. Maxwell → wave equation Black–Scholes → heat equation Schrödinger → complex wave equation Fourier → solves them all Entropy → explains the normal distribution