ixekizumab

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Ligands
ixekizumab

GtoPdb Ligand ID: 7541

Synonyms: LY-2439821 | LY2439821 | Taltz®

ixekizumab is an approved drug (FDA & EMA (2016))

Comment: Ixekizumab binds to IL-17A and blocks its action.
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record. A protein BLAST search using the variable region of the heavy chain of ixekizumab identifies this as sequence 118 from patent US7838638 [1]. In this patent binding affinity data for human IL-17 is provided for several antibody clones, but it does not specify which was chosen as ixekizumab, although mAbs 126, 121 and 104 did undergo additional experimental investigations.

References
1. Allan A, Chow C-K , Liu L, Lu J, Tetreault JW. (2010) Interleukin specific monoclonal antibody for use in treatment and prevention of autoimmune, cell proliferative, inflammatory and developmental disorders. Patent number: US7838638. Assignee: Eli Lilly And Company. Priority date: 13/12/2005. Publication date: 23/11/2010.
2. Blauvelt A, Papp KA, Griffiths CE, Puig L, Weisman J, Dutronc Y, Kerr LF, Ilo D, Mallbris L, Augustin M. (2017) Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3). Am J Clin Dermatol, 18 (2): 273-280. [PMID:28074446]
3. Burkett PR, Kuchroo VK. (2016) IL-17 Blockade in Psoriasis. Cell, 167 (7): 1669. [PMID:27984714]
4. Dong J, Goldenberg G. (2017) New biologics in psoriasis: an update on IL-23 and IL-17 inhibitors. Cutis, 99 (2): 123-127. [PMID:28319618]
5. Farahnik B, Beroukhim K, Zhu TH, Abrouk M, Nakamura M, Singh R, Lee K, Bhutani T, Koo J. (2016) Ixekizumab for the Treatment of Psoriasis: A Review of Phase III Trials. Dermatol Ther (Heidelb), 6 (1): 25-37. [PMID:26910853]
6. Genovese MC, Greenwald M, Cho CS, Berman A, Jin L, Cameron GS, Benichou O, Xie L, Braun D, Berclaz PY et al.. (2014) A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors. Arthritis Rheumatol, 66 (7): 1693-704. [PMID:24623718]
7. Girolomoni G, Mrowietz U, Paul C. (2012) Psoriasis: rationale for targeting interleukin-17. Br J Dermatol, 167 (4): 717-24. [PMID:22716185]
8. Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, Reich K, Amato D, Ball SG, Braun DK et al.. (2016) Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med, 375 (4): 345-56. [PMID:27299809]
9. Krueger JG, Fretzin S, Suárez-Fariñas M, Haslett PA, Phipps KM, Cameron GS, McColm J, Katcherian A, Cueto I, White T et al.. (2012) IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol, 130 (1): 145-54.e9. [PMID:22677045]
10. Nash P, Kirkham B, Okada M, Rahman P, Combe B, Burmester GR, Adams DH, Kerr L, Lee C, Shuler CL et al.. (2017) Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet, 389 (10086): 2317-2327. [PMID:28551073]

References

1. Allan A, Chow C-K , Liu L, Lu J, Tetreault JW. (2010)
Interleukin specific monoclonal antibody for use in treatment and prevention of autoimmune, cell proliferative, inflammatory and developmental disorders.
Patent number: US7838638. Assignee: Eli Lilly And Company. Priority date: 13/12/2005. Publication date: 23/11/2010.

2. Blauvelt A, Papp KA, Griffiths CE, Puig L, Weisman J, Dutronc Y, Kerr LF, Ilo D, Mallbris L, Augustin M. (2017)
Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3).
Am J Clin Dermatol, 18 (2): 273-280. [PMID:28074446]

3. Burkett PR, Kuchroo VK. (2016)
IL-17 Blockade in Psoriasis.
Cell, 167 (7): 1669. [PMID:27984714]

4. Dong J, Goldenberg G. (2017)
New biologics in psoriasis: an update on IL-23 and IL-17 inhibitors.
Cutis, 99 (2): 123-127. [PMID:28319618]

5. Farahnik B, Beroukhim K, Zhu TH, Abrouk M, Nakamura M, Singh R, Lee K, Bhutani T, Koo J. (2016)
Ixekizumab for the Treatment of Psoriasis: A Review of Phase III Trials.
Dermatol Ther (Heidelb), 6 (1): 25-37. [PMID:26910853]

6. Genovese MC, Greenwald M, Cho CS, Berman A, Jin L, Cameron GS, Benichou O, Xie L, Braun D, Berclaz PY et al.. (2014)
A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors.
Arthritis Rheumatol, 66 (7): 1693-704. [PMID:24623718]

7. Girolomoni G, Mrowietz U, Paul C. (2012)
Psoriasis: rationale for targeting interleukin-17.
Br J Dermatol, 167 (4): 717-24. [PMID:22716185]

8. Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, Reich K, Amato D, Ball SG, Braun DK et al.. (2016)
Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis.
N Engl J Med, 375 (4): 345-56. [PMID:27299809]

9. Krueger JG, Fretzin S, Suárez-Fariñas M, Haslett PA, Phipps KM, Cameron GS, McColm J, Katcherian A, Cueto I, White T et al.. (2012)
IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis.
J Allergy Clin Immunol, 130 (1): 145-54.e9. [PMID:22677045]

10. Nash P, Kirkham B, Okada M, Rahman P, Combe B, Burmester GR, Adams DH, Kerr L, Lee C, Shuler CL et al.. (2017)
Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial.
Lancet, 389 (10086): 2317-2327. [PMID:28551073]