drug · small molecule

XPOVIO

updated 2mo ago

by $KPTI Karyopharm Therapeutics Inc.🔗 ChEMBL

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Small molecule drug with a maximum clinical stage of Approval (across all indications), with 3 approved and 29 investigational indications.

targets

Exportin-1

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brand

XPOVIO

trade names

Nexpovio, Xpovio

generic

SELINEXOR

MOA

12.1 Mechanism of Action In nonclinical studies, selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). XPO1 inhibition by selinexor leads to accumulation of TSPs in the nucleus and reductions in several oncoproteins, such as c-myc and cyclin D1, cell cycle arrest, and apoptosis of cancer cells. Selinexor demonstrated pro-apoptotic activity in vitro in multiple myeloma cells and showed anti-tumor activity in murine xenograft models of multiple myeloma and diffuse large B cell lymphoma. The combination of selinexor and dexamethasone or bortezomib demonstrated synergistic cytotoxic effects in multiple myeloma in vitro and increased anti-tumor activity in murine xenograft multiple myeloma models in vivo, including those resistant to proteasome inhibitors.

indication

1 INDICATIONS AND USAGE XPOVIO is a nuclear export inhibitor indicated: In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy ( 1.1 ). In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody ( 1.1 ). For the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s) ( 1.2 ). 1.1 Multiple Myeloma XPOVIO in combination with bortezomib and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. XPOVIO in combination with dexamethasone is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. 1.2 Diffuse Large B-Cell Lymphoma XPOVIO is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate [see Clinical Studies ( 14.2 )] . Continued approval for this indication may be contingent upon verification and description

XPOVIO

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