IP Library › Granted Patent US 12,338,242
Granted Patent B2
US 12,338,242 · App. 17/448,482 · Granted Jun 24, 2025

TYK2 inhibitors and uses thereof

Inventor: Craig E. Masse (Cambridge, MA)
Assignee: Takeda Pharmaceutical Company Limited
C07D487/04C07D519/00
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Quick Facts
Patent No.
US 12,338,242
App. No.
17/448,482
Filed
Sep 22, 2021
Granted
Jun 24, 2025
Kind
B2
Art Unit
1699
USPC
514/248
Abstract

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.

Claims (140)

1. A method of inhibiting TYK2 in a biological sample comprising contacting the sample with a compound of formula XX:

or a pharmaceutically acceptable salt thereof, wherein:

R 3 is —C(O)NH 2 , —C(O)NHR 3A , —C(O)N(R 3A ) 2 , —C(O)OR, —C(O)NHOR, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein said ring is substituted with m instances of R 3B ,

R 6 is hydrogen, R A , or R B ,

R 7 is hydrogen, halogen, —NH 2 , —NHR 7A , or —NHC(O)R 7A ,

or R 6 and R 7 are taken together with their intervening atoms to form a 4-7 membered partially unsaturated, or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein said ring is substituted by p instances of R C ;

R 3A , R 3B , and R 7A are each independently R B , and are each substituted by q instances of R C , wherein two R C substituents on the same carbon are optionally taken together to form a 3-6 membered saturated or partially unsaturated spiro-fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or wherein two R C substituents on adjacent carbons are optionally taken together to form a 3-6 membered saturated or partially unsaturated fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each instance of R A is independently oxo, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —S(O)NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR 2 , —N(R)C(NR) NR 2 , —N(R)S(O) 2 NR 2 , or —N(R)S(O) 2 R;

each instance of R B is independently C1-6 aliphatic, phenyl, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3-7 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each instance of R C is independently oxo, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —S(O)NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR 2 , —N(R)C(NR) NR 2 , —N(R)S(O) 2 NR 2 , or —N(R)S(O) 2 R or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein two optional substituents on the same carbon are optionally taken together to form a 3-6 membered saturated or partially unsaturated spiro-fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or wherein two optional substituents on adjacent carbons are optionally taken together to form a 3-6 membered saturated or partially unsaturated fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each R is independently hydrogen, or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:

two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur;

wherein each hydrogen bound to carbon can be optionally and independently replaced by deuterium; and

each instance of m, n, p, q, and r is independently 0, 1, 2, 3, or 4.

2. A method of treating a TYK2-mediated disorder, disease, or condition in a patient comprising administering to the patient a compound of formula XX:

or a pharmaceutically acceptable salt thereof, wherein:

R 3 is —C(O)NH 2 , —C(O)NHR 3A , —C(O)N(R 3A ) 2 , —C(O)OR, —C(O)NHOR, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein said ring is substituted with m instances of R 3B ,

R 6 is hydrogen, R A , or R B ;

R 7 is hydrogen, halogen, —NH 2 , —NHR 7A , or —NHC(O)R 7A ,

or R 6 and R 7 are taken together with their intervening atoms to form a 4-7 membered partially unsaturated, or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein said ring is substituted by p instances of R C ;

R 3A , R 3B , and R 7A are each independently R B , and are each substituted by q instances of R C , wherein two R C substituents on the same carbon are optionally taken together to form a 3-6 membered saturated or partially unsaturated spiro-fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or wherein two R C substituents on adjacent carbons are optionally taken together to form a 3-6 membered saturated or partially unsaturated fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each instance of R A is independently oxo, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —S(O)NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR 2 , —N(R)C(NR) NR 2 , —N(R)S(O) 2 NR 2 , or —N(R)S(O) 2 R;

each instance of R B is independently C 1-6 aliphatic, phenyl, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3-7 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each instance of R C is independently oxo, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —S(O)NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR 2 , —N(R)C(NR) NR 2 , —N(R)S(O) 2 NR 2 , or —N(R)S(O) 2 R or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein two optional substituents on the same carbon are optionally taken together to form a 3-6 membered saturated or partially unsaturated spiro-fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or wherein two optional substituents on adjacent carbons are optionally taken together to form a 3-6 membered saturated or partially unsaturated fused heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

each R is independently hydrogen, or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:

two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur;

wherein each hydrogen bound to carbon can be optionally and independently replaced by deuterium; and

each instance of m, n, p, q, and r is independently 0, 1, 2, 3, or 4,

wherein the TYK2-mediated disorder, disease, or condition is psoriasis, Crohn's disease, ulcerative colitis, inflammatory bowel disease, asthma, cutaneous lupus erythematosus, systemic lupus erythematosus, or chronic obstructive pulmonary disease.

3. The method of claim 2 , wherein each of R 3A and R 7A is independently R B , and is substituted by q instances of R C , provided that neither of R 3A or R 7A is phenyl.

4. The method of claim 2 , wherein R 7A is C 1-6 aliphatic.

5. The method of claim 2 , wherein R 7 is selected from —NH 2 , —NHMe, —NHCD 3 ,

6. The method of claim 2 , wherein R 3 is selected from

7. The method of claim 2 , wherein R 3 is selected from

8. The method of claim 2 , wherein R 3 is selected from

9. The method of claim 2 , wherein R 3 is selected from

10. The method of claim 2 , wherein R C is selected from

11. A compound selected from one of the following:

I-1 

(racemic)

I-2 

(racemic)

I-3 

I-4 

I-5 

I-6 

I-7 

(enantiopure)

I-8 

(enantiopure)

I-9 

(enantiopure)

I-10

(enantiopure)

I-11

(enantiopure)

I-12

(enantiopure)

I-13

(enantiopure)

I-14

(enantiopure)

I-15

(racemic)

I-16

(racemic)

I-17

I-18

I-19

I-20

I-21

I-22

I-23

I-24

(enantiopure)

I-25

(enantiopure)

I-26

(enantiopure)

I-27

(enantiopure)

I-28

(enantiopure)

I-29

(enantiopure)

I-30

(racemic)

I-31

(racemic)

I-32

(racemic)

I-33

(enantiopure)

I-34

(enantiopure)

I-35

(enantiopure)

I-36

(enantiopure)

I-37

(enantiopure)

I-38

(enantiopure)

I-39

(enantiopure)

I-40

(enantiopure)

I-41

(enantiopure)

I-42

(enantiopure)

I-43

(enantiopure)

I-44

(enantiopure)

I-45

(enantiopure)

I-46

(enantiopure)

I-47

(racemic)

I-48

(enantiopure)

I-49

(enantiopure)

I-50

(racemic)

I-51

(enantiopure)

I-52

(enantiopure)

or a pharmaceutically acceptable salt thereof.

12. The method of claim 2 , wherein the disorder, disease, or condition is psoriasis.

13. The method of claim 2 , wherein the disorder, disease, or condition is Crohn's disease.

14. The method of claim 2 , wherein the disorder, disease, or condition is ulcerative colitis.

15. The method of claim 2 , wherein the disorder, disease, or condition is inflammatory bowel disease.

16. The method of claim 2 , wherein the disorder, disease, or condition is systemic lupus erythematosus.

17. The method of claim 2 , wherein the disorder, disease, or condition is asthma.

18. The method of claim 2 , wherein the disorder, disease, or condition is chronic obstructive pulmonary disease.

19. The method of claim 2 , wherein the endocrine disorder is cutaneous lupus erythematosus.

Assignments (3)
INTERCOMPANY AGREEMENT Recorded Sep 11, 2023
From: NIMBUS LAKSHMI, INC.
To: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Reel/Frame 064867/0415 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 23, 2021
From: MASSE, CRAIG E.
To: NIMBUS DISCOVERY, INC.
Reel/Frame 057581/0515 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 23, 2021
From: NIMBUS DISCOVERY, INC.
To: NIMBUS LAKSHMI, INC.
Reel/Frame 057581/0552 →
Continuity (4)
Division 16750610 · Jan 23, 2020
Provisional Application 62880754 · Jul 31, 2019
Provisional Application 62795735 · Jan 23, 2019
Related Publication 20220073528A1 · Mar 10, 2022
References Cited (91)
US 4650750A · Giese · 1987 [cited by applicant]
US 4709016A · Giese · 1987 [cited by applicant]
US 5360819A · Giese · 1994 [cited by applicant]
US 5516931A · Giese et al. · 1996 [cited by applicant]
US 5602273A · Giese et al. · 1997 [cited by applicant]
US 5604104A · Giese et al. · 1997 [cited by applicant]
US 5610020A · Giese et al. · 1997 [cited by applicant]
US 5650270A · Giese et al. · 1997 [cited by applicant]
US 6552065B2 · Remiszewski et al. · 2003 [cited by applicant]
US 7390799B2 · Bruncko et al. · 2008 [cited by applicant]
US 8138347B2 · Knight et al. · 2012 [cited by applicant]
US 20180155349A1 · Greenwood et al. · 2018 [cited by applicant]
US 20180325899A1 · Weinstein et al. · 2018 [cited by applicant]
US 20200231594A1 · Masse · 2020 [cited by applicant]
JP 2009509961A · 2009 [cited by applicant]
WO 2001042246A2 · 2001 [cited by applicant]
WO 2002088112A1 · 2002 [cited by applicant]
WO 2003063794A2 · 2003 [cited by applicant]
WO 2004019973A1 · 2004 [cited by applicant]
WO 2004089925A1 · 2004 [cited by applicant]
WO 2004106328A1 · 2004 [cited by applicant]
WO 2005007623A2 · 2005 [cited by applicant]
WO 2005113554A2 · 2005 [cited by applicant]
WO 2006078846A1 · 2006 [cited by applicant]
WO 2006122806A2 · 2006 [cited by applicant]
WO 2007016176A2 · 2007 [cited by applicant]
WO 2007038314A2 · 2007 [cited by applicant]
WO 2007044729A2 · 2007 [cited by applicant]
WO 2007053452A1 · 2007 [cited by applicant]
WO 2007070514A1 · 2007 [cited by applicant]
WO 2007084786A1 · 2007 [cited by applicant]
WO 2007129161A2 · 2007 [cited by applicant]
WO 2008039218A2 · 2008 [cited by applicant]
WO 2008109943A1 · 2008 [cited by applicant]
WO 2008118802A1 · 2008 [cited by applicant]
WO 2009100375A1 · 2009 [cited by applicant]
WO 2009114512A1 · 2009 [cited by applicant]
WO 2011090760A1 · 2011 [cited by applicant]
WO 2014074660A1 · 2014 [cited by applicant]
WO 2014074661A1 · 2014 [cited by applicant]
WO 2015026574A1 · 2015 [cited by applicant]
WO 2015089143A1 · 2015 [cited by applicant]
WO 2015131080A1 · 2015 [cited by applicant]
WO 2017087590A1 · 2017 [cited by applicant]
WO 2018067432A1 · 2018 [cited by applicant]
WO 2018093968A1 · 2018 [cited by applicant]
Choy “Clinical significance of Janus Kinase inhibitor selectivity” Rheumatology 2018, pp. 1-10. [cited by examiner]
Barnes “Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease” Pharmacological Reviews 68:788-815, Jul. 2016. [cited by examiner]
Thoma “Selective inhibitors of the Janus kinase Jak3—Are they effective?” Bioorganic & Medicinal Chemistry Letters 24 (2014) 4617-462. [cited by examiner]
Lin “A Novel Selective JAK2 Inhibitor Identified Using Pharmacological Interactions” Frontiers in Pharmacology Dec. 2018 | vol. 9 | Article 1379 pp. 1-14. [cited by examiner]
O'Shea “Janus kinase Inhibitors in autoimmune diseases” Ann Rheum Dis. Apr. 2013 ; 72(0 2): ii111-ii115. [cited by examiner]
Liang “Lead Optimization of a 4-Aminopyridine Benzamide Scaffold To Identify Potent, Selective, and Orally Bioavailable TYK2 Inhibitors” J. Med. Chem. 2013, 56, 4521-4536. [cited by examiner]
Vardiman “The World Health Organization (WHO) classification of the myeloid neoplasms” Blood (2002), 100(7), 2292-2302. [cited by examiner]
Pui “Treatment of Acute Lymphoblastic Leukemia” New England Journal of Medicine 2006, 354, 166-78. [cited by examiner]
FS14 Myelofibrosis Facts | p. 1 Revised Apr. 2012, pp. 1-9. [cited by examiner]
Ocana, A. “Preclinical development of molecular targeted agents for cancer” Nat. Rev. Clin. Oncol. 2011, 8, 200-209. [cited by examiner]
Johnson, et al. “Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials.” British Journal of Cancer 2001, 84, 1424-1431. [cited by examiner]
Makrilakis “Pathophysiology of Type 2 diabetes” Chapter 3 in Diabetes in Clinical Practice: Questions and Answers from Case Studies, Nicholas Katsilambros et al. eds. John Wiley & Sons: 2006, pp. 43-58. [cited by examiner]
University of Cambridge John van Geest Centre for Brain Repair School of Clinical Medicine “Alzheimer's disease and tauopathy” Online “http://www.brc.cam.ac.uk/research/alzheimers-disease-and-tauopathy/” accessed Sep. 1… [cited by examiner]
Tomohiro Chiba “Emerging Therapeutic Strategies in Alzheimer's Disease” Intech 2013, 181-225. [cited by examiner]
Bacon et al., “Interleukin 12 (IL-12) induces tyrosine phosphorylation of Jak2 and Tyk2: differential use of Janus family kinases by IL-2 and IL-12,” The Journal of Experimental Medicine, vol. 181, No. 1, Jan. 1995 (pp.… [cited by applicant]
Ban et al., “Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor,” European Journal of Human Genetics, vol. 17, No. 10, Oct. 2009 (pp. 1309-1313). [cited by applicant]
Berge et al., “Pharmaceutical salts,” Journal Pharmaceutical Sciences, vol. 66, No. 1, Jan. 1977 (pp. 1-19). [cited by applicant]
Cho et al., “Genomics and the multifactorial nature of human auto-immune disease,” The New England Journal Medicine, vol. 365, No. 17, Oct. 2011 (pp. 1612-1623). [cited by applicant]
Cortes et al., “Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci,” Nature Genetics, vol. 45, No. 7, Jul. 2013 (pp. 730-738). [cited by applicant]
Duerr et al., “A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene,” Science, vol. 314, No. 5804, Dec. 2006 (pp. 1461-1463). [cited by applicant]
Finbloom et al., “IL-10 induces the tyrosine phosphorylation of Tyk2 and Jak1 and the differential assembly of Stat1 and Stat3 complexes in human T cells and monocytes,” Journal immunology, vol. 155, No. 3, Aug. 1995 (p… [cited by applicant]
Fontan et al. “Discovering What Makes STAT Signaling TYK in T-ALL,” Cancer Discovery, vol. 3, No. 5, May 2013 (pp. 494-496). [cited by applicant]
Graham et al., “Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with Systemic Lupus Erythematosus,” PLoS Genetics, vol. 7, No. 10, Oct. 2011 (9 pages). [cited by applicant]
Harel et al., “Pharmacologic inhibition of JAK-STAT signaling promotes hair growth,” Science Advances, vol. 1, No. 9, Oct. 2015 (12 pages). [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2020/014746, dated Apr. 14, 2020 (12 pages). [cited by applicant]
Ishizaki et al., “Tyk2 deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice,” International Immunology, vol. 23, No. 9, Sep. 2011 (pp. 575-582). [cited by applicant]
Ishizaki et al., “Tyk2 is a therapeutic target for psoriasis-like skin inflammation,” International Immunology, vol. 26, No. 5, Dec. 2013 (pp. 257-267). [cited by applicant]
Moslin et al., “Identification of imidazo[1,2-b]pyridazine TYK2 pseudokinase ligands as potent and selective allosteric inhibitors of TYK2 signalling,” Med. Chem. Commun., vol. 8, 2017, pp. 700-712. [cited by applicant]
Oyamada et al., “Tyrosine Kinase 2 Plays Critical Roles in the Pathogenic CD4 T Cell Responses for the Development of Experimental Autoimmune Encephalomyelitis,” Journal of Immunology, vol. 183, No. 11, Dec. 2009 (pp. 7… [cited by applicant]
Parham et al., “A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rß1 and a novel cytokine receptor subunit, IL-23R,” Journal of Immunology, vol. 168, No. 11, Jun. 2002 (pp. 5699-5708). [cited by applicant]
Ramirez et al., “Defining Causative Factors Contributing in the Activation of Hedgehog Signaling in Diffuse Large B-Cell Lymphoma,” Leukemia Research, vol. 36, No. 10, Oct. 2012 (pp. 1267-1273). [cited by applicant]
Remmers et al., “Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease,” Nature Genetics, vol. 42, No. 8, Aug. 2010 (pp. 698-702). [cited by applicant]
Rostovtsev et al., “A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective ”Ligation“ of Azides and Terminal Alkynes,” Angew. Chem. Int. Ed., vol. 41, No. 14, Jul. 2002 (pp. 2596-2599). [cited by applicant]
Sanda et al. “TYK2-STAT1-BCL2 Pathway Dependence in T-Cell Acute Lymphoblastic Leukemia,” Cancer Discovery, vol. 3, No. 5, May 2013 (pp. 564-577). [cited by applicant]
Sigurdsson et al., “Polymorphisms in the Tyrosine Kinase 2 and Interferon Regulatory Factor 5 Genes Are Associated with Systemic Lupis Erythematosus,” American Journal of Human Genetics, vol. 76, No. 3, Mar. 2005 (pp. 5… [cited by applicant]
Simma et al., “Identification of an Indispensable Role for Tyrosine Kinase 2 in CTL-Mediated Tumor Surveillance,” Cancer Research, vol. 69, No. 1, Jan. 2009 (pp. 203-211). [cited by applicant]
Stahl et al., “Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6ß receptor components,” Science, vol. 263, No. 5143, Jan. 1994 (pp. 92-95). [cited by applicant]
Strange et al., “A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1,” Nature Genetics, vol. 42, No. 11, Nov. 2010 (pp. 985-990). [cited by applicant]
STN Registry database entry for CAS RN 1797511-85-3, Entered STN, Jul. 8, 2015, Accessed Feb. 13, 2021. [cited by applicant]
Sun et al., “Carbohydrate and protein immobilization onto solid surfaces by sequential Diels-Alder and azide-alkyne cycloadditions,” Bioconjugate Chemistry, vol. 17, No. 1, Jan.-Feb. 2006 (52-57). [cited by applicant]
Velasquez et al., “A protein kinase in the interferon a/ß signaling pathway,” Cell, vol. 70, No. 2, Jul. 1992 (pp. 313-322). [cited by applicant]
Wan et al. “Tyk/STAT3 Signaling Mediates ß-Amyloid-Induced Neuronal Cell Death: Implications in Alzheimer's Disease,” Journal of Neuroscience, vol. 30, No. 20, May 2010 (pp. 6873-6881). [cited by applicant]
Welham et al., “Interleukin-13 signal transduction in lymphohemopoietic cells: similarities and differences in signal transduction with interleukin-4 and insulin,” The Journal of Biological chemistry, vol. 270, No. 20, … [cited by applicant]
Xing et al., “Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition,” Nature Medicine, vol. 20, No. 9, Sep. 2014 (pp. 1043-1049). [cited by applicant]
Zhang et al., “Docking protein Gab2 regulates mucin expression and goblet cell hyperplasia through TYK2/STAT6 pathway,” The FASEB Journal, vol. 26, No. 11, Nov. 2012 (pp. 4603-4613). [cited by applicant]