programmed cell death 1 ligand 1

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Ligands
programmed cell death 1 ligand 1 (Human)

GtoPdb Ligand ID: 9606

Abbreviated name: PD-L1

Synonyms: B7 homolog 1 | B7-H1 | PDL1 | programmed death ligand 1

Compound class: Endogenous peptide in human, mouse or rat

Comment: This is one of the ligands for the PD-1 receptor. It is a single-pass type I membrane protein. The PD-L1/PD-1 interaction is an established immune checkpoint. Both the ligand and receptor are targets for novel immuno-oncology therapeutics, as over-expression of either of these proteins is a mechanism used by tumour cells to evade immune detection and destruction. Already the target of approved immunotherapeutics in the form of monoclonal antibodies, small molecules targeting the PD-1/PD-L1 checkpoint are now in development to address the shortcomings associated with the current antibody therapies (including, poor susceptibility rate to single immune checkpoint pathway inhibitors, long half-life of antibodies and association with the development of adverse events, problems connected to the requirement for intravenous infusions) [7,16].

Species: Human

References
1. Chupak LS, Ding M, Martin SW, Zheng X, Hewawasam P, Connolly TP, Xu N, Yeung K-S, Zhu J, Langley DR, et al.. (2015) Compounds useful as immunomodulators. Patent number: WO2015160641A2. Assignee: Bristol-Myers Squibb Company. Priority date: 14/04/2014. Publication date: 22/10/2015.
2. Conesa-Milián L, Falomir E, Murga J, Carda M, Marco JA. (2019) Novel multitarget inhibitors with antiangiogenic and immunomodulator properties. Eur J Med Chem, 170: 87-98. [PMID:30878834]
3. Dietl A, Ralser A, Pelka K. (2024) Dual checkpoint T(h1)eamwork makes the anti-cancer dream work. Immunity, 57 (3): 406-408. [PMID:38479356]
4. Feng Z, Chen X, Zhang L, Yang Y, Laifangfang, Ji M, Zhou C, Zheng Y, Xue N, Li L. (2017) Bromo benzyl ether derivative, preparation method therefor, and pharmaceutical composition and uses thereof =. Patent number: WO2017202275A1. Assignee: Institute of Pharmaceutical Research, Chinese Academy of Medical Sciences. Priority date: 23/05/2016. Publication date: 30/11/2017.
5. Gong J, Cao J, Zhang Q, Xu N, Zhao Y, Xing B, Miao Z, Wu Y, Pan H, Gao Q et al.. (2022) Safety, antitumor activity and biomarkers of sugemalimab in Chinese patients with advanced solid tumors or lymphomas: results from the first-in-human phase 1 trial. Cancer Immunol Immunother, 71 (8): 1897-1908. [PMID:34984540]
6. Greaves P, Gribben JG. (2013) The role of B7 family molecules in hematologic malignancy. Blood, 121 (5): 734-44. [PMID:23223433]
7. Guzik K, Zak KM, Grudnik P, Magiera K, Musielak B, Törner R, Skalniak L, Dömling A, Dubin G, Holak TA. (2017) Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1. J Med Chem, 60 (13): 5857-5867. [PMID:28613862]
8. Irving B, Chiu H, Maecker H, Mariathasan S, Lehar SM, Wu Y, Cheung J. (2012) Anti-PD-L1 antibodies, compositions and articles of manufacture. Patent number: US8217149. Assignee: Genentech, Inc.. Priority date: 09/12/2008. Publication date: 10/07/2012.
9. Janakiram M, Abadi YM, Sparano JA, Zang X. (2012) T cell coinhibition and immunotherapy in human breast cancer. Discov Med, 14 (77): 229-36. [PMID:23114578]
10. Jochems C, Tritsch SR, Pellom ST, Su Z, Soon-Shiong P, Wong HC, Gulley JL, Schlom J. (2017) Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824). Oncotarget, 8 (43): 75217-75231. [PMID:29088859]
11. Johnson DB, Rioth MJ, Horn L. (2014) Immune checkpoint inhibitors in NSCLC. Curr Treat Options Oncol, 15 (4): 658-69. [PMID:25096781]
12. Lu J, Lee-Gabel L, Nadeau MC, Ferencz TM, Soefje SA. (2015) Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy. J Oncol Pharm Pract, 21 (6): 451-67. [PMID:24917416]
13. Miao X, Xu R, Fan B, Chen J, Li X, Mao W, Hua S, Li B. (2018) PD-L1 reverses depigmentation in Pmel-1 vitiligo mice by increasing the abundance of Tregs in the skin. Sci Rep, 8 (1): 1605. [PMID:29371688]
14. Nastri HG, Iffland C, Leger O, An Q, Cartwright M, Mckenna SD, Sood VD, Hao G. (2013) Anti-pd-l1 antibodies and uses thereof. Patent number: WO2013079174 A1. Assignee: Merck Patent Gmbh. Priority date: 28/11/2011. Publication date: 06/06/2013.
15. Queva C, Morrow M, Hammond S, Alimzhanov M, Babcock J, Foltz I, Kang JS, Sekirov L, Boyle M, Chodorge M. (2011) Targeted binding agents against b7-h1. Patent number: WO2011066389. Assignee: Medimmmune, Limited, Astrazeneca Ab, Amgen British Columbia, Medimmune, Llc. Priority date: 24/11/2009. Publication date: 03/06/2011.
16. Sasikumar PG, Ramachandra M. (2017) Small-molecule antagonists of the immune checkpoint pathways: concept to clinic. Future Med Chem, 9 (12): 1305-1308. [PMID:28771036]
17. Sun C, Yin M, Cheng Y, Kuang Z, Liu X, Wang G, Wang X, Yuan K, Min W, Dong J et al.. (2023) Novel Small-Molecule PD-L1 Inhibitor Induces PD-L1 Internalization and Optimizes the Immune Microenvironment. J Med Chem, 66 (3): 2064-2083. [PMID:36579489]
18. Tang PA, Heng DY. (2013) Programmed death 1 pathway inhibition in metastatic renal cell cancer and prostate cancer. Curr Oncol Rep, 15 (2): 98-104. [PMID:23263823]
19. Wu L, Li J, Qi C, Zhang F, Li Z, Zhu W, Xiao K, Lu L, Mei S, Qian DQ et al.. (2018) Benzooxazole derivatives as immunomodulators. Patent number: WO2018119266A1. Assignee: Incyte Corporation. Priority date: 22/12/2016. Publication date: 28/06/2018.
20. Xu Y, Du H, Guo W, Liu B, Yan W, Zhang C, Qin L, Huang J, Wang H, Wu S et al.. (2024) Discovery of Highly Potent Small-Molecule PD-1/PD-L1 Inhibitors with a Novel Scaffold for Cancer Immunotherapy. J Med Chem, 67 (5): 4083-4099. [PMID:38348878]
21. Zhang F, Wei H, Wang X, Bai Y, Wang P, Wu J, Jiang X, Wang Y, Cai H, Xu T et al.. (2017) Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade. Cell Discov, 3: 17004. [PMID:28280600]

References

1. Chupak LS, Ding M, Martin SW, Zheng X, Hewawasam P, Connolly TP, Xu N, Yeung K-S, Zhu J, Langley DR, et al.. (2015)
Compounds useful as immunomodulators.
Patent number: WO2015160641A2. Assignee: Bristol-Myers Squibb Company. Priority date: 14/04/2014. Publication date: 22/10/2015.

2. Conesa-Milián L, Falomir E, Murga J, Carda M, Marco JA. (2019)
Novel multitarget inhibitors with antiangiogenic and immunomodulator properties.
Eur J Med Chem, 170: 87-98. [PMID:30878834]

3. Dietl A, Ralser A, Pelka K. (2024)
Dual checkpoint T(h1)eamwork makes the anti-cancer dream work.
Immunity, 57 (3): 406-408. [PMID:38479356]

4. Feng Z, Chen X, Zhang L, Yang Y, Laifangfang, Ji M, Zhou C, Zheng Y, Xue N, Li L. (2017)
Bromo benzyl ether derivative, preparation method therefor, and pharmaceutical composition and uses thereof =.
Patent number: WO2017202275A1. Assignee: Institute of Pharmaceutical Research, Chinese Academy of Medical Sciences. Priority date: 23/05/2016. Publication date: 30/11/2017.

5. Gong J, Cao J, Zhang Q, Xu N, Zhao Y, Xing B, Miao Z, Wu Y, Pan H, Gao Q et al.. (2022)
Safety, antitumor activity and biomarkers of sugemalimab in Chinese patients with advanced solid tumors or lymphomas: results from the first-in-human phase 1 trial.
Cancer Immunol Immunother, 71 (8): 1897-1908. [PMID:34984540]

6. Greaves P, Gribben JG. (2013)
The role of B7 family molecules in hematologic malignancy.
Blood, 121 (5): 734-44. [PMID:23223433]

7. Guzik K, Zak KM, Grudnik P, Magiera K, Musielak B, Törner R, Skalniak L, Dömling A, Dubin G, Holak TA. (2017)
Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1.
J Med Chem, 60 (13): 5857-5867. [PMID:28613862]

8. Irving B, Chiu H, Maecker H, Mariathasan S, Lehar SM, Wu Y, Cheung J. (2012)
Anti-PD-L1 antibodies, compositions and articles of manufacture.
Patent number: US8217149. Assignee: Genentech, Inc.. Priority date: 09/12/2008. Publication date: 10/07/2012.

9. Janakiram M, Abadi YM, Sparano JA, Zang X. (2012)
T cell coinhibition and immunotherapy in human breast cancer.
Discov Med, 14 (77): 229-36. [PMID:23114578]

10. Jochems C, Tritsch SR, Pellom ST, Su Z, Soon-Shiong P, Wong HC, Gulley JL, Schlom J. (2017)
Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824).
Oncotarget, 8 (43): 75217-75231. [PMID:29088859]

11. Johnson DB, Rioth MJ, Horn L. (2014)
Immune checkpoint inhibitors in NSCLC.
Curr Treat Options Oncol, 15 (4): 658-69. [PMID:25096781]

12. Lu J, Lee-Gabel L, Nadeau MC, Ferencz TM, Soefje SA. (2015)
Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy.
J Oncol Pharm Pract, 21 (6): 451-67. [PMID:24917416]

13. Miao X, Xu R, Fan B, Chen J, Li X, Mao W, Hua S, Li B. (2018)
PD-L1 reverses depigmentation in Pmel-1 vitiligo mice by increasing the abundance of Tregs in the skin.
Sci Rep, 8 (1): 1605. [PMID:29371688]

14. Nastri HG, Iffland C, Leger O, An Q, Cartwright M, Mckenna SD, Sood VD, Hao G. (2013)
Anti-pd-l1 antibodies and uses thereof.
Patent number: WO2013079174 A1. Assignee: Merck Patent Gmbh. Priority date: 28/11/2011. Publication date: 06/06/2013.

15. Queva C, Morrow M, Hammond S, Alimzhanov M, Babcock J, Foltz I, Kang JS, Sekirov L, Boyle M, Chodorge M. (2011)
Targeted binding agents against b7-h1.
Patent number: WO2011066389. Assignee: Medimmmune, Limited, Astrazeneca Ab, Amgen British Columbia, Medimmune, Llc. Priority date: 24/11/2009. Publication date: 03/06/2011.

16. Sasikumar PG, Ramachandra M. (2017)
Small-molecule antagonists of the immune checkpoint pathways: concept to clinic.
Future Med Chem, 9 (12): 1305-1308. [PMID:28771036]

17. Sun C, Yin M, Cheng Y, Kuang Z, Liu X, Wang G, Wang X, Yuan K, Min W, Dong J et al.. (2023)
Novel Small-Molecule PD-L1 Inhibitor Induces PD-L1 Internalization and Optimizes the Immune Microenvironment.
J Med Chem, 66 (3): 2064-2083. [PMID:36579489]

18. Tang PA, Heng DY. (2013)
Programmed death 1 pathway inhibition in metastatic renal cell cancer and prostate cancer.
Curr Oncol Rep, 15 (2): 98-104. [PMID:23263823]

19. Wu L, Li J, Qi C, Zhang F, Li Z, Zhu W, Xiao K, Lu L, Mei S, Qian DQ et al.. (2018)
Benzooxazole derivatives as immunomodulators.
Patent number: WO2018119266A1. Assignee: Incyte Corporation. Priority date: 22/12/2016. Publication date: 28/06/2018.

20. Xu Y, Du H, Guo W, Liu B, Yan W, Zhang C, Qin L, Huang J, Wang H, Wu S et al.. (2024)
Discovery of Highly Potent Small-Molecule PD-1/PD-L1 Inhibitors with a Novel Scaffold for Cancer Immunotherapy.
J Med Chem, 67 (5): 4083-4099. [PMID:38348878]

21. Zhang F, Wei H, Wang X, Bai Y, Wang P, Wu J, Jiang X, Wang Y, Cai H, Xu T et al.. (2017)
Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade.
Cell Discov, 3: 17004. [PMID:28280600]