Compound class:
Synthetic organic
Comment: EG-001's chemical structure was derived from that of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib [1], but it does not inhibit BTK or any other kinase. It has potent anti-proliferative and anti-tumour effects in vivo, against a wide range of lymphomas and leukaemias. A preprint has reported the molecular mechanism of EG-001 [2]; it acts to convert the auto-inhibited (closed) form of the Wiskott-Aldrich syndrome protein (WASp; WAS; P42768) to its activated allosteric conformation. WASp is one of a family of actin/cytoskeleton-regulating proteins that is expressed only in cells of haematopoietic origin. Activated WASp increases actin polymerisation (via interactions with the Arp2/3 complex), induces cytoskeleton reorganisation, and promotes cell death.
|
|
References |
1. Gaudio E, Bertoni F, Pazzi N, Guala M. (2019)
New compounds with enhanced anti-tumor effects. Patent number: WO2019185117A1. Assignee: Fondazione Per L'istituto Oncologico Di Ricerca (Ior). Priority date: 26/03/2018. Publication date: 03/10/2019. |
2. Spriano F, Sartori G, Barnabei L, Arribas AJ, Guala M, Carrasco del Amor MA, Tomasso MR, Tarantelli C. Cascione L et al.. (2022)
A first-in-class Wiskott-Aldrich syndrome protein (WASp) activator with anti-tumor activity in hematological cancers. biorxiv, Preprint. DOI: 10.1101/2022.11.25.517686 |