Delving into the Latest Updates on WRX606 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

mTORC1

Mechanism

mTORC1 inhibitors(Mammalian target of Rapamycin (mTORC1) inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Riken Corp.

Active Organization

Riken Corp.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Cancer-specific metabolic alterations hyperactivate the kinase activity of the mammalian/mechanistic target of rapamycin (mTOR) for overcoming stressful environments. Rapalogs, which allosterically inhibit mTOR complex 1 (mTORC1), have been approved as anticancer agents. However, the immunosuppressive side effect of these compounds results in the promotion of tumor metastasis, thereby limiting their therapeutic efficacy. We first report a nonrapalog inhibitor, WRX606, identified by a hybrid strategy of in silico and in cell selections. Our studies showed that WRX606 formed a ternary complex with FK506-binding protein-12 (FKBP12) and FKBP-rapamycin-binding (FRB) domain of mTOR, resulting in the allosteric inhibition of mTORC1. WRX606 inhibited the phosphorylation of not only the ribosomal protein S6 kinase 1 (S6K1) but also eIF4E-binding protein-1 (4E-BP1). Hence, WRX606 efficiently suppressed tumor growth in mice without promotion of metastasis. These results suggest that WRX606 is a potent lead compound for developing anticancer drugs discovered by in silico and in cell methods.

100 Deals associated with WRX606

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