Sulanemadlin Explained

Drug Name:	Sulanemadlin
Width:	300px
Legal Status:	Investigational
Synonyms:	ALRN-6924
Cas Number:	1451199-98-6
Pubchem:	164182053
Unii:	6BGF28R54M
Drugbank:	DB17285
C:	95
H:	140
N:	20
O:	23

Sulanemadlin (development code ALRN-6924) is an experimental drug for the treatment of cancer.^[1] It is under development by Aileron Therapeutics, and has been studied in clinical trials for myelodysplastic syndrome and acute myeloid leukemia.^[2]

Sulanemadlin is a stapled peptide that mimics the N-terminal domain of p53, a tumor suppressor protein. As such, it binds to MDM2 and MDMX, leading to tumor cell apoptosis.^[3]

Clinical trials

Sulanemadlin is notable as the first stapled peptide, a novel pharmaceutical strategy, to enter clinical trials.^{[1] [4]}

Despite its preclinical promise, concerns about side effects, including severe neutropenia, have terminated Phase 1B clinical trials early in at least one trial.^[5]

Notes and References

1. Guerlavais V, Sawyer TK, Carvajal L, Chang YS, Graves B, Ren JG, Sutton D, Olson KA, Packman K, Darlak K, Elkin C, Feyfant E, Kesavan K, Gangurde P, Vassilev LT, Nash HM, Vukovic V, Aivado M, Annis DA . Discovery of Sulanemadlin (ALRN-6924), the First Cell-Permeating, Stabilized α-Helical Peptide in Clinical Development . Journal of Medicinal Chemistry . 66 . 14 . 9401–9417 . July 2023 . 37439511 . 10.1021/acs.jmedchem.3c00623 .
2. Web site: Stapled peptide sulanemadlin for AML and MDS . Sallman D . 17 December 2018 . The Video Journal of Hematological Oncology (VJHemOnc) . Magdalen Medical Publishing (MMP) .
3. Web site: MDM2/MDMX inhibitor ALRN-6924 . NCI Drug Dictionary . .
4. Web site: The Stapled Peptide That Made It Furthest . Lowe D . Derek Lowe (chemist) . In The Pipeline, Science Magazine . American Association for the Advancement of Science (AAAS) . July 27, 2023 .
5. Web site: Phase 1b Trial of ALRN-6924 for p53-Mutated Breast Cancer Terminated . Targeted Oncology . 18 April 2024 . en . 22 February 2023.