Natick, MA, United States
Natick, MA, United States

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Patent
Karyopharm Therapeutics | Date: 2014-06-20

The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds of formula (I) or their pharmaceutically acceptable salts, and methods of using said compounds, salts and compositions in the treatment of various disorders associated with CRM1 activity.


Patent
Karyopharm Therapeutics | Date: 2014-07-03

The invention generally relates to substituted benzofuranyl and substituted benzoxazolyl compounds, and more particularly to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of Structural Formula (A), or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment of cancer (e.g., mantle cell lymphoma), and other diseases and disorders.


Patent
Karyopharm Therapeutics | Date: 2016-01-06

The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds of formula I, and methods of using said compounds, salts and compositions in the treatment of various disorders associated with CRM1 activity.


Patent
Karyopharm Therapeutics | Date: 2015-06-10

The invention generally relates to nuclear transport modulators, e.g., CRM1 inhibitors, and more particularly to a compound represented by structural formula I: or a pharmaceutically acceptable salt thereof, wherein the values and alternative values for the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of structural formula I, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment, modulation and/or prevention of physiological conditions associated with CRM1 activity.


Patent
Karyopharm Therapeutics and Catholic University of Leuven | Date: 2014-03-14

The invention generally relates to nuclear transport modulators, e.g., CRM1 inhibitors, and, more particularly, to a compound represented by structural formula (I), or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of structural formula I, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment, modulation and/or prevention of physiological conditions associated with CRM1 activity.


Patent
Karyopharm Therapeutics | Date: 2015-11-13

The invention generally relates to nuclear transport modulators, e.g., CRM1 inhibitors, and more particularly to a compound represented by structural formula I: or a pharmaceutically acceptable salt thereof, wherein the values and alternative values for the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of structural formula I, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment, modulation and/or prevention of physiological conditions associated with CRM1 activity.


Patent
Karyopharm Therapeutics | Date: 2014-03-14

The invention generally relates to the use of nuclear transport modulators, e.g., CRM1 inhibitors, and more particularly to a compound represented by structural formula (I) or a pharmaceutically acceptable salt thereof, wherein Ring A, X, R^(1), R^(2 )and n are as defined and described herein, in a method for promoting wound healing in a subject.


Patent
Karyopharm Therapeutics | Date: 2015-06-23

The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds of formula I, and methods of using said compounds, salts and compositions in the treatment of various disorders associated with CRM1 activity.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2016

DESCRIPTION provided by applicant Systemic lupus erythematosus SLE is a complex autoimmune disease with a broad spectrum of clinical manifestations affecting several organs and associated with dysregulation of the immune system This disease affects millions of individuals with women and underserved minorities disproportionately burdened It is associated with significant morbidity and mortality yet treatment approaches remain broadly immunosuppressive anti inflammatory or palliative Despite the considerable progress on understanding SLE immune pathogenesis only one drug has been approved for the treatment of lupus patients in the last years emphasizing the urgent need for novel therapies Considering the central role of auto antibodies in the amplification of auto immunity a goal in lupus therapy is the elimination of auto reactive antibody secreting cells ASC Karyopharm Therapeutics has pioneered the development of Selective Inhibitors of Nuclear Export SINE compounds and wishes to investigate their potential utility in auto immune diseases In collaboration with the Anolik laboratory at the University of Rochester Medical Center we will evaluate a novel approach to the treatment of autoimmune disease that targets the generation and survival of autoreactive plasma cells PCs via inhibition of nuclear export SINE compounds have a potent effect on the generation of splenic T follicular helper cells TFH and germinal center GC B cells and selectively inhibit production of auto reactive ASCs specific for double stranded DNA SINEs had a compelling effect on GC formation stability prevented expansion of memory TFH and B cells and markedly reduced mRNA expression of molecules critical for survival and recruitment of auto reactive ASC including certain cytokines interleukin and interferon induced chemokines Thus SINE drugs strongly and selectively ablated auto reactive PCs by targeting pathways that are critical for their generation and survival recruitment into inflamed kidneys In the proposed project we will define the efficacy of SINE compounds in SLE in order to accelerate the translation of these novel compounds into lupus clinical trials In Aim we will identify the optimal treatment strategy of SINE compounds in murine SLE model by i refining the dose and time required for GCs and PCs to exhibit a response in vivo ii optimizing the induction treatment strategy and iii determining the duration of SINE compound effect and define the need for maintenance therapy In Aim we will examine the protective immunity effects of the SINE compounds by i evaluating the immune responses in murine SLE during treatment and ii determining the recovery of protective immune responses after cessation of therapy Successful completion of these studies will lead to a Phase II proposal to move SINE compounds into extensive preclinical safety testing in preparation for clinical trials The goal is to develop an efficacious dosing strategy using a novel treatment approach that targets key synergistic pathways in SLE disease pathogenesis with the long term goal of delivering an improved therapy for SLE and other autoimmune diseases PUBLIC HEALTH RELEVANCE Systemic Systemic lupus erythematosus SLE is a complex autoimmune disease affecting multiple organs and with limited treatment options We seek to investigate the potential utility of Selective Inhibitors of Nuclear Export SINE compounds in auto immune diseases like SLE


Patent
Karyopharm Therapeutics | Date: 2014-03-19

The invention generally relates to nuclear transport modulators, e.g., CRM1 inhibitors, and more particularly to a compound represented by structural formula I: or a pharmaceutically acceptable salt thereof, wherein the values and alternative values for the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of structural formula I, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment, modulation and/or prevention of physiological conditions associated with CRM1 activity.

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