Gridegalutamide Explained

Cas Number:	2446929-86-6
Pubchem:	153513643
Unii:	VA228VR2DI
Kegg:	D12866
Synonyms:	BMS-986365; CC-94676
Iupac Name:	2-[(2R)-4-[2-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-ethylphenoxy]ethyl]-2-methylpiperazin-1-yl]-N-[3-[[(3R)-2,6-dioxopiperidin-3-yl]amino]phenyl]acetamide| chemical_formula = | C=41 | H=45 | F=3 | N=8 | O=5 | S=1| molecular_weight = | SMILES = CCC1=C(C=CC(=C1)N2C(=S)N(C(=O)C2(C)C)C3=CC(=C(C=C3)C#N)C(F)(F)F)OCCN4CCN([C@@H](C4)C)CC(=O)NC5=CC=CC(=C5)N[C@@H]6CCC(=O)NC6=O| Jmol = | StdInChI = InChI=1S/C41H45F3N8O5S/c1-5-26-19-31(52-39(58)51(38(56)40(52,3)4)30-10-9-27(22-45)32(21-30)41(42,43)44)11-13-34(26)57-18-17-49-15-16-50(25(2)23-49)24-36(54)47-29-8-6-7-28(20-29)46-33-12-14-35(53)48-37(33)55/h6-11,13,19-21,25,33,46H,5,12,14-18,23-24H2,1-4H3,(H,47,54)(H,48,53,55)/t25-,33-/m1/s1| StdInChI_comment = | StdInChIKey = YUVGVJYLOFTILT-INJOXJOKSA-N| density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation =

Gridegalutamide is an investigational oral androgen receptor (AR) degrader being developed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). It belongs to a class of drugs called proteolysis targeting chimeras (PROTACs), which are designed to selectively degrade specific proteins by hijacking the ubiquitin-proteasome system.^{[1] [2]} CC-94676 employs a unique dual mechanism of action, combining AR degradation with AR antagonism, potentially offering advantages over traditional AR inhibitors in overcoming resistance mechanisms.^[3] Initially developed by Celgene and now under Bristol Myers Squibb, CC-94676 has demonstrated AR protein degradation and suppression of tumor growth in CRPC mouse models. As of 2024, CC-94676 is being evaluated in phase I clinical trials for patients with mCRPC who have progressed on androgen-deprivation therapy and at least one prior secondary hormonal therapy.

Notes and References

1. Salama AK, Trkulja MV, Casanova E, Uras IZ . Targeted Protein Degradation: Clinical Advances in the Field of Oncology . International Journal of Molecular Sciences . 23 . 23 . December 2022 . 15440 . 36499765 . 9741350 . 10.3390/ijms232315440 . free .
2. Xie H, Liu J, Alem Glison DM, Fleming JB . The clinical advances of proteolysis targeting chimeras in oncology . Exploration of Targeted Anti-tumor Therapy . 2 . 6 . 511–521 . 2021 . 36046114 . 9400722 . 10.37349/etat.2021.00061 .
3. Rathkopf DE, Patel MR, Choudhury AD, Rasco D, Lakhani N, Hawley JE, Srinivas S, Aparicio A, Narayan V, Runcie KD, Emamekhoo H, Reichert ZR, Nguyen MH, Wells AL, Kandimalla R, Liu C, Suryawanshi S, Han J, Wu J, Arora VK, Pourdehnad M, Armstrong AJ . Safety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer . Annals of Oncology . September 2024 . 39293515 . 10.1016/j.annonc.2024.09.005 . free .