USA flag logo/image

An Official Website of the United States Government

Therapeutic Inhibition of MIF in Rheumatoid Arthritis

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2012 / SBIR
Agency Tracking Number:
R44AR056908
Solicitation Year:
2012
Solicitation Topic Code:
NIAMS
Solicitation Number:
PA11-096
Small Business Information
L2 DIAGNOSTICS, LLC
BOX 8175 NEW HAVEN, CT -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 2012
Title: Therapeutic Inhibition of MIF in Rheumatoid Arthritis
Agency: HHS
Contract: 2R44AR056908-02A1
Award Amount: $988,799.00
 

Abstract:

DESCRIPTION (provided by applicant): The long-term product goal of this project is a small molecule therapeutic to treat rheumatoid arthritis (RA), which acts by reducing the inflammatory response triggered by the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF). Since MIF is an upstream regulator of the inflammatory cascade, small molecule therapeutics targeting MIF activity are expected to provide effective treatment for RA, which currently afflicts 4 million people in the US alone and for which there is no curative therapy. To this end, in Phase I of this SBIR project, we screened 200,000 compounds for MIF inhibitors and identified a number of small molecules that block MIF-driven cellular activation pathways that are associated withthe immunopathology of RA. For this proposal we selected two inhibitors that are structurally unique and possess functional groups that have not been previously associated with MIF inhibitory activity. They appear to interact with MIF by distinct mechanisms, and they are not cytotoxic to mammalian cells. In the continuation of this project, we propose to elucidate their precise mechanisms of action by obtaining MIF-inhibitor co-crystal structures. Further, using medicinal chemistry guided by structural data, we propose to obtain structure-activity relationships and modify the compounds to improve their MIF-inhibitory activities in an effort to obtain molecules that are efficacious in the RA mouse model. All of these efforts are expected to yield a lead compound suitable for further development towards a small molecule therapeutic for RA. PUBLIC HEALTH RELEVANCE: The goal of this project is to advance a promising small molecule compound towards development into a new drug for the treatment of rheumatoidarthritis (RA), a disease that afflicts up to 4 million people in the US. This compound appears to inhibit the inflammatory component of RA that is caused by the cytokine macrophage migration inhibitory factor (MIF). Since MIF acts upstream in the inflammatory cascade in RA, inhibition of this activity will address many of the downstream effector pathways that are ultimately responsible for joint destruction.

Principal Investigator:

Karen G. Anthony
203-503-0383
kanthony@L2dx.com

Business Contact:

Martin J. Mattessich
203-393-9439
mmattessich@L2dx.com
Small Business Information at Submission:

L2 DIAGNOSTICS, LLC
BOX 8175 NEW HAVEN, CT -

EIN/Tax ID: 106150994
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No