GRWD5769
| Clinical data | |
|---|---|
| Drug class | ERAP1 inhibitor |
GRWD5769 is a first-in-class anti-cancer drug which acts as a selective inhibitor of the enzyme endoplasmic reticulum aminopeptidase 1 (ERAP1). It is in human clinical trials for the treatment of solid tumours including squamous cell carcinoma and cervical and liver cancers.[1][2][3][4][5] Grey Wolf Therapeutics has filed several patents claiming phenylsulfamoyl benzoic acid derivatives as selective ERAP1 inhibitors useful in the treatment of cancer,[6][7] but the exact chemical structure of GRWD5769 does not appear to have been disclosed as yet.[8][9][10]
References
[edit]- ↑ Leishman A, Paes W, Coulson R, Pinggera M, Sette J, Anderton K, et al. (15 June 2022). "A small molecule approach to drive novel neoantigen generation: First-in-class inhibitors of ERAP1 generate novel neoantigens driving anti-tumor effects". Cancer Research. 82 (12_Supplement): 2065. doi:10.1158/1538-7445.AM2022-2065.
- ↑ Leishman A, Paes W, Sparrow E, Ribeiro A, Cundell M, Aleksic M, et al. (4 April 2023). "GRWD5769: A first-in-class inhibitor of ERAP1, generating novel cancer antigens to drive de novo anti-tumor T cell responses". Cancer Research. 83 (7_Supplement): 3467. doi:10.1158/1538-7445.AM2023-3467.
- ↑ Lillie T, Kichenadasse G, Liu J, Hernandez Guerrero T, Calvo E, Jakobsson H, et al. (2024). "EMITT-1: Proof-of-mechanism immunopeptidome (ImPD) effects at target PK exposure, in a phase 1 study of GRWD5769 (a first-in-class inhibitor of Endoplasmic Reticulum Aminopeptidase 1 [ERAP1]) in patients with solid malignancies". J Clin Oncol. 42 (16): 2589. doi:10.1200/JCO.2024.42.16_suppl.2589.
- ↑ Liu JJ, Kichenadasse G, Guerrero TH, Calvo E, Gan HK, Markman B, et al. (1 September 2025). "1561P EMITT-1: Final clinical, PK & PD data from dose escalation and selection of recommended dose for expansion cohorts in a phase I study of GRWD5769 (a first-in-class ERAP1i) in patients with solid malignancies". Annals of Oncology. 36: S931–2. doi:10.1016/j.annonc.2025.08.2191.
- ↑ Thistlethwaite F, Roda D, Castanon Alvarez E, Moreno V, Hernandez Guerrero T, García-Corbacho J, et al. (2026). "EMITT-1: Clinical and pharmacodynamic activity with the oral ERAP1 inhibitor GRWD5769 and cemiplimab in 6 completed phase 1b expansion cohorts in solid tumors with anti–PD-1 resistance or MSS-CRC". J Clin Oncol. 44 (16): 2500. doi:10.1200/JCO.2026.44.16_suppl.2500.
- ↑ CA 3117916, Quibell MG, Patel AL, Shiers JJ, Sparenberg MG, Joyce PI, "Compounds", published 2019-11-22, assigned to Grey Wolf Therapeutics Ltd [Gb] and Grey Wolf Therapeutics Limited
- ↑ US 20240366595, Quibell M, Shiers JJ, Sparenberg M, "Phenyl-sulfamoyl.benzoyc acids as erap1 modulators", published 2024-04-29, assigned to Grey Wolf Therapeutics Ltd
- ↑ Maben Z, Arya R, Rane D, An WF, Metkar S, Hickey M, et al. (January 2020). "Discovery of Selective Inhibitors of Endoplasmic Reticulum Aminopeptidase 1". Journal of Medicinal Chemistry. 63 (1): 103–121. doi:10.1021/acs.jmedchem.9b00293. PMC 8218592. PMID 31841350.
- ↑ Fougiaxis V, Barcherini V, Petrovic MM, Sierocki P, Warenghem S, Leroux F, et al. (15 December 2024). "First fragment-based screening identifies new chemotypes inhibiting ERAP1-metalloprotease". European Journal of Medicinal Chemistry. 280 116926. doi:10.1016/j.ejmech.2024.116926. PMID 39369482.
- ↑ Fougiaxis V, He B, Khan T, Vatinel R, Koutroumpa NM, Afantitis A, et al. (25 July 2024). "ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights". Journal of Medicinal Chemistry. 67 (14): 11597–11621. doi:10.1021/acs.jmedchem.4c00840. PMC 11284793. PMID 39011823.