Chemistry:GRWD5769
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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]
See also
References
- ↑ "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. 15 June 2022. doi:10.1158/1538-7445.AM2022-2065.
- ↑ "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. 4 April 2023. doi:10.1158/1538-7445.AM2023-3467.
- ↑ "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. 2024. doi:10.1200/JCO.2024.42.16_suppl.2589.
- ↑ "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. 1 September 2025. doi:10.1016/j.annonc.2025.08.2191.
- ↑ "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. 2026. doi:10.1200/JCO.2026.44.16_suppl.2500.
- ↑ Quibell MG, Patel AL, Shiers JJ, Sparenberg MG, Joyce PI, "Compounds", CA patent 3117916, published 2019-11-22, assigned to Grey Wolf Therapeutics Ltd [Gb]and Grey Wolf Therapeutics Limited
- ↑ Quibell M, Shiers JJ, Sparenberg M, "Phenyl-sulfamoyl.benzoyc acids as erap1 modulators", US patent 20240366595, published 2024-04-29, assigned to Grey Wolf Therapeutics Ltd
- ↑ "Discovery of Selective Inhibitors of Endoplasmic Reticulum Aminopeptidase 1". Journal of Medicinal Chemistry 63 (1): 103–121. January 2020. doi:10.1021/acs.jmedchem.9b00293. PMID 31841350.
- ↑ "First fragment-based screening identifies new chemotypes inhibiting ERAP1-metalloprotease". European Journal of Medicinal Chemistry 280. 15 December 2024. doi:10.1016/j.ejmech.2024.116926. PMID 39369482.
- ↑ "ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights". Journal of Medicinal Chemistry 67 (14): 11597–11621. 25 July 2024. doi:10.1021/acs.jmedchem.4c00840. PMID 39011823.
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