PF-06700841 Tosylate is the p-toluenesulfonate salt of brepocitinib, the dual TYK2 and JAK1 inhibitor Pfizer took through a wide autoimmune programme. Catalogs list it under CAS 1883299-62-4 (free base), and that parenthesis matters: the number belongs to the parent, not the salt.
The PF-06700841 chemical structure centres on an aminopyrimidine that reads the kinase hinge, with an N-methylpyrazole on one side and a rigid 3,8-diazabicyclo[3.2.1]octane linking it to an (S)-2,2-difluorocyclopropyl carboxamide. The gem-difluorocyclopropane is the unusual piece: a small, stereodefined cap tuning potency and metabolic stability.
Salt formation changes mass, not pharmacology: free base runs 389.41 g/mol against 561.61 for the tosylate, so only about 69% of what you weigh is drug. Databases index the unhyphenated PF 06700841 too.
Application of PF-06700841 Tosylate
This compound answers one question: what happens when TYK2 and JAK1 are blocked together while JAK2 is left mostly alone?
The combination is deliberate. Together they carry most inflammatory cytokine traffic in psoriasis, lupus and bowel disease. JAK2 is the one to avoid: it runs erythropoietin, thrombopoietin and GM-CSF, and shutting it down brings cytopenias.
Which brings the caveat. The window over JAK2 is roughly threefold to fivefold, not the hundredfold gap the word selective implies. Push into the high nanomolar range and JAK2 joins in, so a phenotype at 1 micromolar is not clean TYK2 and JAK1 pharmacology. Titrate against the enzyme numbers.
It pairs usefully with deucravacitinib: one binds the ATP site, the other stabilises the TYK2 pseudokinase domain, so running both separates active-site inhibition from allosteric control of one kinase.
In Vitro
Enzyme potency lands at 22.7 nM for TYK2 and 16.8 nM for JAK1, against 76.6 nM for JAK2 and 6490 nM for JAK3. The JAK3 gap is real selectivity; the JAK2 gap is only a working margin. Human whole blood gives the ladder: PF-06700841 blocks IFN-alpha driven pSTAT3 near 30 nM, IL-12 driven pSTAT4 at 65 nM, IL-23 driven pSTAT3 at 120 nM. One oddity: IL-6 splits by readout, pSTAT1 in CD3 positive cells falling near 81 nM, pSTAT3 needing 641 nM.
In Vivo
The in vivo record here is clinical rather than murine, unusual for a catalogue compound. Phase 1 ran single doses to 200 mg and daily doses to 175 mg without triggering stopping rules. In psoriasis patients dosed 28 days, placebo-adjusted PASI fell 9.6 points at 30 mg and 14.2 at 100 mg, benefit lasting about a month after the last dose. A phase 2b in psoriatic arthritis then hit ACR50, PASI75 and PASI90 significance at 30 and 60 mg. PF-06700841 went on into phase 2 across alopecia areata, ulcerative colitis, lupus and vitiligo.
Biochemical and Physiological Actions
Janus kinases work in pairs beneath cytokine receptors, phosphorylating each other and then the STAT proteins that carry signal inward. The PF-06700841 structure fills the ATP pocket of the catalytic domain, so inhibition is ATP-competitive and catches any pair including TYK2 or JAK1.
Pairing explains the selectivity logic. TYK2 partners JAK2 for IL-12 and IL-23, JAK1 for type I interferon; JAK1 partners JAK2 for IL-6 and JAK3 for gamma-chain cytokines. Catching two of four silences a wide but defined set, while JAK2 homodimer receptors keep working.
Features and Benefits of PF-06700841 Tosylate
PF-06700841 Tosylate suits a narrow set of jobs:
- Dual TYK2 and JAK1 coverage in one ATP-competitive molecule.
- Published whole blood potencies for translational anchoring.
- A clinical dataset across several indications.
- Room-temperature handling, no shipping restrictions.
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