Sharon Shacham, Karyopharm's founder, Chief Scientific Officer, and head of research and development commented, "This broad and growing list of publications demonstrates the potential for our novel, oral CRM1
antagonists - SINEs - to restore the body's own anti-cancer TSPs to the cell nucleus, where they can carry out their tumor killing function.
Romero Garzon, MD, PhD, and colleagues at the Ohio State University published a plenary paper in the journal Blood entitled, "Pre-clinical activity of a novel CRM1 inhibitor in acute myeloid leukemia" (PubMed ID: 22677130).
This paper describes the discovery of the SINE compounds based on the X-ray crystal structure of CRM1 using proprietary in silico screening methods developed by Karyopharm's founder, Chief Scientific Officer and head of research and development, Sharon Shacham, PhD, MBA.
Karyopharm's first program is directed towards the Selective Inhibition of Nuclear Export - its SINE program - targeting CRM1, a major non-redundant nuclear export protein.
Cheryl London of Ohio State University will present "Preliminary results of a phase I study of the novel CRM1 inhibitors KPT-276 and KPT-335 in dogs with spontaneous cancer" on Tuesday, April 3, 2012 in the Poster Section: Late-Breaking Research: Clinical Trials (8:00 AM - 12:00 PM), Hall F (Abstract LB-232; Section 40).
Roberto Fragomeni and James Cusack of Massachusetts General Hospital will present "Potent anticancer activity against both BRAF-mutant and BRAF wild-type melanoma cell lines using a novel CRM1 nuclear export inhibitor" (Abstract 1914; Section 34).
a leader in the new field of nuclear transport modulators, announces seven presentations by collaborators covering its Selective Inhibitors of Nuclear Export (SINE) modulators of the CRM1 protein at the American Society of Hematology (ASH) meeting on December 10-13, 2011, in San Diego.
John Byrd at the Ohio State University, will discuss the role of CRM1 inhibition in the treatment of CLL on Monday, December 12, at 7:45 AM.
Ken Anderson's lab at Dana Farber Cancer Institute will present "Blockade of Nuclear Export Protein CRM1 (chromosomal region maintenance 1, XPO1) by a Novel, Potent and Selective CRM1 Inhibitor KPT-185 Induces Significant Antitumor Activity Against Human MM"
Michael Wang from the MD Anderson Cancer Center will present "Novel CRM1 Inhibitors for Therapy In Mantle Cell Lymphoma," a form of NHL.
Many cargo proteins that depend on CRM1 for nuclear export, such as p53, Bcr-Abl and FOXO-3a, function as tumor suppressors or transcription factors that protect normal cells by regulating cell growth and apoptosis (cell death).
Abstract 1591: "Mechanistic Analyses of the Therapeutic Activity of Nuclear Export Inhibitors (NEIs) in Cancer" presented data demonstrating a direct correlation between target (CRM1) occupancy and the downstream consequences of CRM1 inhibition, including nuclear export inhibition and cytotoxicity.