Preclinical Data

JAK Pathway | Explore JAK signaling, one pathway involved in cytokine-mediated cellular processes

Preclinical Data

JAK Signaling in Disease | Some key disease-related cytokines that signal through the JAK pathway

Preclinical Data

Preclinical Data | Cytokine inhibition profiles of Pfizer JAK inhibitors that informed clinical research efforts

Preclinical Data

Pfizer I&I Pipeline | Scientific innovation and discovery in Inflammation & Immunology1,2,a

Pfizer I&I Pipeline | Scientific innovation and discovery in JAK inhibitors1,2,a

JAK PATHWAY JAK PATHWAY JAK PATHWAY
Select to view pathway changes caused by JAK inhibitors
Examples of cytokines that signal through the JAK pathway2-4
Cytokine
type JAK
enzyme
pairings Cellular
processes
Gamma-chain family cytokines (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21)
JAK PATHWAY
Inflammation, growth/ maturation of immune cells, differentiation of T-cells and natural killer cells
Type I IFNs (IFN-α/β) IL-10 family (IL-10, IL-20, IL-22)
JAK PATHWAY
Antiviral, inflammation, antitumor activity
IL-6, IL-11, IL-13, IL-27, IL-31, IL-35, OSM, LIF
JAK PATHWAY
Naive T-cell differentiation, T-cell regulation, inflammation
Type II IFN (IFN-γ), TSLP
JAK PATHWAY
Antiviral, inflammation, antimycobacterial activity, differentiation of T- cells
IL-12, IL-23
JAK PATHWAY
Innate immunity, differentiation of T-cells, inflammation activity, differentiation of T-cells
Explore disease-related cytokines
that signal through the JAK pathway
Select a
therapeutic
area
DERMATOLOGY1-11,a
JAK PATHWAY JAK PATHWAY
RHEUMATOLOGY1-17,a
JAK PATHWAY JAK PATHWAY
GASTROENTEROLOGY1-5,a
JAK PATHWAY JAK PATHWAY
DERMATOLOGY1-11,a
JAK PATHWAY JAK PATHWAY

Some of these cytokines have been observed to play a role in certain disease states. Select a tappable cytokine to learn more.

JAK PATHWAY
ALOPECIA
AREATA
IFN-γ IL-2 IL-15 IL-21
JAK PATHWAY
VITILIGO
IFN-γ IL-15
JAK PATHWAY
ATOPIC
DERMATITIS
IL-4 IL-13 IL-22
IL-24 IL-31 TSLP
JAK PATHWAY
PLAQUE
PSORIASIS
IL-7 IL-12 IL-15 IL-19
IL-20 IL-22 IL-23 IL-24
JAK PATHWAY
HIDRADENITIS
SUPPURATIVA
IL-6 IL-23
RHEUMATOLOGY1-17,a
JAK PATHWAY JAK PATHWAY
GASTROENTEROLOGY1-5,a
JAK PATHWAY JAK PATHWAY

Some of these cytokines have been observed to play a role in certain disease states. Select a clickable cytokine on the left to learn more.

Explore preclinical cytokine
inhibition by Pfizer JAK inhibitors
Slider Plots blue Slider Plots orange Slider Plots green Slider Plots red Slider Plots
Select up to 4 compounds below to view the different cytokine inhibition profiles.1-4
Compound
Color
PF-06826647 TYK2 inhibitor
Ritlecitinib (PF-06651600) JAK3/TEC inhibitor
Brepocitinib (PF-06700841) TYK2/JAK1 inhibitor
Abrocitinib (PF-04965842) JAK1 inhibitor
Cytokine inhibition profiles are based on preclinical data and are not a representation of clinical efficacy.

About the data

These profiles represent the ability of a compound to inhibit a specific biological or biochemical function in vitro. Whole blood assays were used to assess JAK inhibition by stimulating cells with cytokines and measuring the level of STAT phosphorylation.4,5 It is important to note that these plots may vary between assays depending on the parameters of the assay, such as the dose of compound used or the cytokines measured.6,7 Additionally, many factors other than preclinical selectivity are relevant to the clinical profile of a JAK inhibitor.6,8 These additional factors also influence the effectiveness and safety of a JAK inhibitor in the clinical setting.6-8

Explore JAK inhibitors in the Pfizer I&I pipeline

Swipe left or right to view the diferent phases.

DERMATOLOGY

Over 5 compounds under investigation in multiple dermatology disease states
DISEASE STATE

alopecia areata

VITILIGO

atopic dermatitis

plaque psoriasis

STASIS DERMATITIS

HIDRADENITIS SUPPURATIVA

PHASE 1
PHASE 2
Recruiting
JAK3/
TECb

INHIBITOR

Completed
TYK2/
JAKc,d

INHIBITOR

Active, not recruiting
JAK3/
TEC

INHIBITOR

Active, not recruiting
TYK2/
JAK1d

INHIBITOR

Recruiting
TYK2/
JAK1g

INHIBITOR

Recruiting
PDE4

INHIBITOR

Recruiting
TYK2

INHIBITOR

Recruiting
TYK2/
JAK1g

INHIBITOR

Recruiting
PDE4

INHIBITOR

Recruiting
PDE4h

INHIBITOR

Recruiting
IRAK4

INHIBITOR

Recruiting
TYK2

INHIBITOR

Recruiting
TYK2/
JAK1d

INHIBITOR

PHASE 3
Recruiting
JAK3/
TECb,e,f

INHIBITOR

Recruiting
PDE4g

INHIBITOR

Recruiting
JAK1e

INHIBITOR

GASTROENTEROLOGY

Over 3 compounds under investigation in multiple gastroenterology disease states
DISEASE STATE

crohn's disease

ulcerative colitis

NAFLD/NASHk

PHASE 1
Completed
DGAT2

INHIBITOR

Recruiting
JAK3/
TEC

INHIBITOR

Recruiting
TYK2/
JAK1d

INHIBITOR

Recruiting
IL-10j

IMMUNO-
CYTOKINE

Recruiting
TNFSF15

BLOCKER

Recruiting
JAK3/
TEC

INHIBITOR

Recruiting
TYK2/
JAK1d

INHIBITOR

Completed
ACCi+
DGAT2

INHIBITOR

Completed
ACCj

INHIBITOR

Recruiting
KHK

INHIBITOR

PHASE 3

RHEUMATOLOGY

Over 6 compounds under investigation in multiple rheumatology disease states
DISEASE STATE

DERMATOMYOSITIS

Lupus

PSORIATIC ARTHRITIS

Rheumatoid arthritis

SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

JUVENILE IDIOPATHIC ARTHRITIS

PHASE 1
Recruiting
CHEMOKINE

INHIBITOR

Recruiting
IFNB1

BLOCKER

More info coming soon
IFNB1

BLOCKER

Recruiting
TYK2/
JAK1d

INHIBITOR

Active, not recruiting
TYK2/
JAK1d

BLOCKER

No information available
IL-10l

IMMUNO-
CYTOKINE

Recruiting
JAK3/
TECm

INHIBITOR

Recruiting
IRAK4

INHIBITOR

Recruiting
JAK1/
JAK3n

INHIBITOR

Recruiting
IRAK4+
JAK1/
TECm

INHIBITORS

Recruiting
IRAK4+
JAK1/
JAK3n

INHIBITORS

Recruiting
JAK1/
JAK3

INHIBITOR

Recruiting
JAK1/
JAK3o

INHIBITOR

JAK inhibitors

Select to reveal the diversity of our JAK inhibitor program

IFN=interferon; IL=interleukin; JAK=Janus kinase; LIF=leukemia inhibitory factor; OSM=oncostatin M; P=phosphorylation; STAT=signal transducer and activator of transcription; TSLP=thymic stromal lymphopoietin; TYK=tyrosine kinase.

References: 1. Doginton DW, et al. Trends Endocrinol Metab. 2018;29(1):55-65. 2. Bao L, et al. JAKSTAT. 2013;2(3):e24137. 3. Clark JD, et al. J Med Chem. 2014;57(12):5023-5038. 4. Breakthroughs.com. Cytokines of interest: understanding their paths to disease. https://breakthroughs.com/biology-explained/cytokines-interest-understanding-their-paths-disease. Accessed June 16, 2020. 5. Hodge JA, et al. Clin Exp Rheumatol. 2016;34(2):318-328. 6. Hsu L, Armstrong AW. J Immunol Res. 2014:283617. 7. Danese S, et al. Am J Physiol Gastrointest Liver Physiol. 2016;310(3):G155-162.

IFN=interferon; IL=interleukin; JAK=Janus kinase; TSLP=thymic stromal lymphopoietin.

aThis may not be a complete representation of all disease states under investigation in the Pfizer Inflammation & Immunology pipeline.

References: 1. Solimani F, et al. Front Immunol. 2019;10:2847. 2. Welsch K, et al. Eur J Immunol. 2017;47(7):1096-1107. 3. Triyangkulsri K, Suchonwanit P. Drug Des Devel Ther. 2018;12:2323-2335. 4. Damsky W, King BA. J Am Acad Dermatol. 2017;76(4):736-744. 5. Frisoli ML, et al. Annu Rev Immunol. 2020;38:621-648. 6. Howell MD, et al. Front Immunol. 2019;10:2342. 7. Mitamura Y, et al. Allergol Int. 2020 Jan 21 [epub ahead of print]. 8. Kumari S, et al. Immunity. 2013;39(5):899-911. 9. Wang F, et al. Br J Dermatol. 2012;167(1):92-102. 10. Krueger J, et al. J Allergy Clin Immunol. 2016;137(4):1079-1090. 11. Richmond JM, et al. Sci Transl Med. 2018;10(450):eaam7710. 12. Pollard KM, et al. Discov Med. 2013;16(87):123-131. 13. Bao L, et al. JAKSTAT. 2013;2(3):e24137. 14. Xing L, et al. Nat Med. 2014;20(9):1043-1049. 15. Schlapbach C, et al. J Am Acad Dermatol. 2011;65(4):790-798. 16. Fotiadou C, et al. Psoriasis (Auckl). 2018;8:1-5. 17. Leng RX, et al. Arch Med Res. 2010;41(3):221-225. 18. Suzuki E, et al. Autoimmun Rev. 2014;13(4-5):496-502. 19. Salas A, et al. Nat Rev Gastroenterol Hepatol. 2020;17:323-337. 20. Műzes G, et al. World J Gastroenterol. 2012;18(41):5848-5861. 21. Hawro T, et al. Allergy. 2014;69(1):113-117. 22. Furue M, et al. Allergy. 2018;73(1):29-36. 23. Hao J-Q. Inflammation. 2014;37(1):94-99. 24. Cianferoni A, Spergel J. Expert Rev Clin Immunol. 2014;10(11):1463-1474. 25. Han N-R, et al. J Invest Dermatol. 2014;134(10):2521-2530. 26. Bracaglia C, et al. Pediatr Rheumatol Online J. 2017;15:5. 27. Crayne CB, et al. Front Immunol. 2019;10:119. 28. Throm AA, et al. JCI Insight. 2018;3(15):e121544.

GM-CSF=granulocyte-macrophage colony-stimulating factor; IFN=interferon; IL=interleukin; JAK=Janus kinase.

aThis may not be a complete representation of all disease states under investigation in the Pfizer Inflammation & Immunology pipeline.

References: 1. Rönnblom L, Leonard D. Lupus Sci Med. 2019;6(1):e000270. 2. Crow MK. J Immunol. 2014;192(12):5459-5468. 3. Leng RX, et al.Arch Med Res. 2010;41(3):221-225. 4. Alunno A, et al. Cells. 2019;8(8):898. 5. Sharif MN, et al. Immunol. 2004;172(10):6476-6481. 6. Huang Z, et al. Pediatrics. 2019;143(5):e20182845. 7. Bracaglia C, et al. Pediatr Rheumatol Online J. 2017;15:5. 8. Crayne CB, et al. Front Immunol. 2019;10:119. 9. Akioka S. Mod Rheumatol. 2019;29(2):275-286. 10. Throm AA, et al. JCI Insight. 2018;3(15):e121544. 11. Cutolo M. Ther Adv Musculo. 2013;5(1):3-11. 12. Kim KW, et al. Arthritis Rheum. 2012;64(4):1015-1023. 13. Yoshida Y, Tanaka T. Biomed Res Int. 2014;2014:698313. 14. Lotfi N, et al. Front Immunol. 2019;10:1265. 15. Chen M, Sheng-Ming D. Chin Med J (Engl). 2020;133(8):959-967. 16. Veale DJ, et al. Lancet. 2018;391(10136):2273-2284. 17. Deng X-M, et al. Cell Mol Immunol. 2015;12(1):31-39. 18. Dinesh P, Rasool M. J Cell Physiol. 2018;233(5):3918-3928. 19. Yuan F-L, et al. Mol Biol Rep. 2011;38(3):1717-1721. 20. Suzuki E, et al. Autoimmun Rev. 2014;13(4-5):496-502. 21. Salas A, et al. Nat Rev Gastroenterol Hepatol. 2020;17:323-337. 22. Műzes G, et al. World J Gastroenterol. 2012;18(41):5848-5861. 23. Solimani F, et al. Front Immunol. 2019;10:2847. 24. Schlapbach C, et al. J Am Acad Dermatol. 2011;65(4):790-798. 25. Fotiadou C, et al. Psoriasis (Auckl). 2018;8:1-5. 26. Pollard KM, et al. Discov Med. 2013;16(87):123-131. 27. Damsky W, King BA. J Am Acad Dermatol. 2017;76(4):736-744. 28. Avci AB, et al. Clin Exp Rheumatol. 2016;34(4 suppl 98):39-44. 29. Cornish AL, et al. Nat Rev Rheumatol. 2009;5(10):554-559.

IFN=interferon; IL=interleukin; JAK=Janus kinase.

aThis may not be a complete representation of all disease states under investigation in the Pfizer Inflammation & Immunology pipeline.

References: 1. Salas A, et al. Nat Rev Gastroenterol Hepatol. 2020;17:323-337. 2. Műzes G, et al. World J Gastroenterol. 2012;18(41):5848-5861. 3. Fragoulis GE, et al. Rheumatology (Oxford). 2019;58(Suppl 1):i43-i54. 4. Schwartz DM, et al. Nat Rev Drug Discov. 2017;17(1):78. 5. De Vries LCS, et al. J Crohns Colitis. 2017;11(7):885-893. 6. Nielsen OH, et al. Scand J Gastroenterol. 2003;38(2):180-185. 7. Heller J, et al. Gastroenterology. 2005;129(2):550-564. 8. Hoving JC. Front Cell Infect Microbiol. 2018;8:395. 9. Solimani F, et al. Front Immunol. 2019;10:2847. 10. Schlapbach C, et al. J Am Acad Dermatol. 2011;65(4):790-798. 11. Fotiadou C, et al. Psoriasis (Auckl). 2018;8:1-5. 12. Leng RX, et al. Arch Med Res. 2010;41(3):221-225. 13. Suzuki E, et al. Autoimmun Rev. 2014;13(4-5):496-502.

EPO=erythropoietin; IFN=interferon; IL=interleukin; JAK=Janus kinase; STAT=signal transducer and activator of transcription; TEC=tyrosine kinase expressed in hepatocellular carcinoma; TYK=tyrosine kinase.

References: 1. Pfizer pipeline. Pfizer website. https://www.pfizer.com/science/drug-product-pipeline. Published October 27, 2020. Accessed November 4, 2020.
2. Telliez JB, et al. ACS Chem Biol. 2016;11(12):3442-3451. 3. Vazquez ML, et al. J Med Chem. 2018;61(3):1130-1152. 4. Fensome A, et al. J Med Chem. 2018;61(19):8597-8612. 5. Clark JD, et al. J Med Chem. 2014;57(12):5023-5038. 6. Choy EH. Rheumatology (Oxford). 2019;58(6):953-962. 7. Danese S, et al. Gut. 2019;68(10):1893-1899. 8. Schwartz DM, et al. Nat Rev Drug Discov. 2017;16(12):843-862. Data on file. Pfizer Inc, New York, NY.

Efficacy and safety of these compounds, for the uses identified within, have not been established and are currently under investigation. Regulatory approval of any of these compounds or uses is dependent on the completion of the study programs and review and approval by regulatory authorities. This is not a complete representation of all Pfizer pipeline compounds. This information is current as of October 27, 2020. The clinical trial information is available at www.clinicaltrials.gov.

ACCi=acetyl-CoA carboxylase inhibitor; DGAT2=diacylglycerol acyltransferase 2; IL=interleukin; INFB1=interferon beta 1; IRAK=interleukin-1 receptor-associated kinase; JAK=Janus kinase; KHK=ketohexokinase; NAFLD=non-alcoholic fatty liver disease; NASH=non-alcoholic steatohepatitis; PDE=phosphodiesterase; TEC=tyrosine kinase expressed in hepatocellular carcinoma; TNFSF15=tumor necrosis factor superfamily member 15;
TYK=tyrosine kinase.

aAs of October 27, 2020.
bRitlecitinib, a JAK3/TEC inhibitor, is being evaluated in phase 2 and phase 3 studies.
cPhase 2 study with brepocitinib (PF-06700841) and ritlecitinib (PF-06651600).
dThe oral formulation of brepocitinib (PF-06700841) is being evaluated in this study.
ePhase 2b/3 and phase 3 trials with ritlecitinib (PF-06651600), not all of which are currently enrolling.
fRitlecitinib (PF-06651600; for alopecia areata) and abrocitinib (PF-04965842; for atopic dermatitis) received Breakthrough Therapy designation from the FDA.
gThe topical formulation of brepocitinib (PF-06700841) is being evaluated in this study.
hStudy with crisaborole.
iMultiple phase 3 trials with abrocitinib (PF-04965842).
jPfizer has an exclusive license from Philogen to develop this compound.
kNAFLD and NASH are metabolic disorders that are included here under gastroenterology for their relevance to the gastroenterology community. The NAFLD/NASH indication can be found within the internal medicine
pipeline.
lThis study is being sponsored by Philogen. Pfizer has an exclusive license to develop this compound.
mMultiple phase 2 trials with ritlecitinib (PF-06651600), not all of which are currently enrolling.
nTofacitinib is under investigation in combination with PF-06650833 and serves as an active comparator.
oPhase 2/3 study with tofacitinib.

References: 1.. Pfizer pipeline. Pfizer website. https://www.pfizer.com/science/drug-product-pipeline. Published October 27, 2020. Accessed November 4, 2020. 2. Study to assess efficacy, safety, tolerability and pharmacokinetics of PF-07038124 ointment in participants with atopic dermatitis or plaque psoriasis (EMPORIA). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT04664153. Published December 11, 2020. Updated January 15, 2021. Accessed January 28, 2021.

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