growth differentiation factor 15   Click here for help

GtoPdb Ligand ID: 9735

Abbreviated name: GDF15
Synonyms: macrophage inhibitory cytokine-1 | MIC-1 | MIC1 | PTGFB
Compound class: Endogenous peptide in human, mouse or rat
Comment: GDF15 is a TGFβ family protein. A commentary on the function(s) of GDF15 was published in 2017 [8]. Experimental evidence indicates that the biological effects of GDF15 are mediated by signalling via a GFRAL/Ret complex [4,7-8,10].
GDF15 promotes nausea and vomiting (emesis), and elevated levels have been associated with pregnancy-induced morning sickness and the risk of hyperemesis gravidarum [5]. Disrupting the formation or function of the GDF15/GFRAL/Ret complex is a mechanism being explored for the mitigation of chemotherapy-induced nausea, cachexia and malaise [1,6,9]. GDF15/GFRAL signalling is also a major driver of nausea, elevated catabolism and weight loss in patients with advanced cancer [2-3].
Species: Human
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
References
1. Borner T, Tinsley IC, Milliken BT, Doebley SA, Najjar NR, Kerwood DJ, De Jonghe BC, Hayes MR, Doyle RP. (2023)
Creation of a Peptide Antagonist of the GFRAL-RET Receptor Complex for the Treatment of GDF15-Induced Malaise.
J Med Chem, 66 (16): 11237-11249. [PMID:37506293]
2. Breen DM, Kim H, Bennett D, Calle RA, Collins S, Esquejo RM, He T, Joaquim S, Joyce A, Lambert M et al.. (2020)
GDF-15 Neutralization Alleviates Platinum-Based Chemotherapy-Induced Emesis, Anorexia, and Weight Loss in Mice and Nonhuman Primates.
Cell Metab, 32 (6): 938-950.e6. [PMID:33207247]
3. da Fonseca GWP, Sato R, de Nazaré Nunes Alves MJ, von Haehling S. (2023)
Current advancements in pharmacotherapy for cancer cachexia.
Expert Opin Pharmacother, 24 (5): 629-639. [PMID:36995115]
4. Emmerson PJ, Wang F, Du Y, Liu Q, Pickard RT, Gonciarz MD, Coskun T, Hamang MJ, Sindelar DK, Ballman KK et al.. (2017)
The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL.
Nat Med, 23 (10): 1215-1219. [PMID:28846098]
5. Fejzo M, Rocha N, Cimino I, Lockhart SM, Petry C, Kay RG, Burling K, Barker P, George AL, Yasara N et al.. (2023)
Fetally-encoded GDF15 and maternal GDF15 sensitivity are major determinants of nausea and vomiting in human pregnancy.
biorxiv, Preprint. DOI: 10.1101/2023.06.02.542661
6. Lee BY, Jeong J, Jung I, Cho H, Jung D, Shin J, Park JK, Park E, Noh S, Shin S et al.. (2023)
GDNF family receptor alpha-like antagonist antibody alleviates chemotherapy-induced cachexia in melanoma-bearing mice.
J Cachexia Sarcopenia Muscle, 14 (3): 1441-1453. [PMID:37017344]
7. Mullican SE, Lin-Schmidt X, Chin CN, Chavez JA, Furman JL, Armstrong AA, Beck SC, South VJ, Dinh TQ, Cash-Mason TD et al.. (2017)
GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates.
Nat Med, 23 (10): 1150-1157. [PMID:28846097]
8. O'Rahilly S. (2017)
GDF15-From Biomarker to Allostatic Hormone.
Cell Metab, 26 (6): 807-808. [PMID:29195860]
9. Suriben R, Chen M, Higbee J, Oeffinger J, Ventura R, Li B, Mondal K, Gao Z, Ayupova D, Taskar P et al.. (2020)
Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice.
Nat Med, 26 (8): 1264-1270. [PMID:32661391]
10. Yang L, Chang CC, Sun Z, Madsen D, Zhu H, Padkjær SB, Wu X, Huang T, Hultman K, Paulsen SJ et al.. (2017)
GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand.
Nat Med, 23 (10): 1158-1166. [PMID:28846099]