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Overview

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Endocrinology and Metabolic Disease

Other Diseases

Small molecule drug

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Endocrinology and Metabolic Disease	1

Top 5 Drug Type	Count

Small molecule drug	2

Top 5 Target	Count

GABAA receptor(Gamma-aminobutyric acid A receptor)	1
α-glucosidase(Acidic alpha-glucosidase)	1

alpha-Difluoromethylornithine (DFMO; eflornithine), an inhibitor of polyamine biosynthesis, was used to treat 14 patients with late stage gambiense sleeping sickness, 12 cases having been previously treated with and considered refractory to melarsoprol. alpha-Difluoromethylornithine was administered intravenously at a dose of 400 mg/kg/day for 14 days followed by oral treatment, 300 mg/kg/day, for 21-28 days. In all patients treatment was associated with rapid disappearance of trypanosomes from body fluids (in several cases within 24 hr) and decreased cerebrospinal fluid white blood cell counts. In all but one patient, who died of a pulmonary infection during treatment, alpha-difluoromethylornithine produced a dramatic reversal of clinical signs and symptoms of the disease. Determination of drug concentrations in serum and cerebrospinal fluid of 5 patients demonstrated that alpha-difluoromethylornithine diffuses into the central nervous system with cerebrospinal fluid levels representing up to 51% of corresponding serum concentrations. Diarrhea, abdominal pain, and anemia were the most frequent side effects associated with therapy, but were reversible and did not necessitate discontinuation of treatment. Four patients have been followed for more than 2 years post-treatment without evidence of relapse.

01 Jan 1987·The American Journal of Tropical Medicine and HygieneQ4 · MEDICINE

Effects of the Ornithine Decarboxylase Inhibitors Dl-α-Difluoromethylornithine and α-Monofluoromethyldehydroornithine Methyl Ester Alone and in Combination with Suramin against Trypanosoma brucei brucei Central Nervous System Models

Q4 · MEDICINE

Article

Author: Clarkson, A. B. ; McCann, P. P. ; Bacchi, C. J. ; Nathan, H. C. ; Sjoerdsma, A. ; Bitonti, A. J. ; Bienen, E. J.

Two ornithine decarboxylase inhibitors, DL-alpha-difluoromethylornithine (eflornithine; DFMO) and a-monofluoromethyldehydroornithine methyl ester (delta MFMO X CH3) were compared in their ability to cure two distinct Trypanosoma brucei brucei central nervous system murine model infections. Both inhibitors cured the TREU 667 and LUMP 1001 isolates if used in combination with a single (20 mg/kg) injection of suramin, a trypanocide in current clinical use. The curative dose of delta MFMO X CH3 in combination with suramin was 1.09 g/kg/day, administered in the drinking water for 14 days; used with suramin, the curative dose of DFMO was 5.3 g/kg/day for 14 days (5 times the delta MFMO X CH3 dose required). In host animals, delta MFMO X CH3 was not toxic and was accumulated by trypanosomes 6-8 times faster than DFMO. Since DFMO by itself has been highly effective against T. b. gambiense infections in humans (12-15 g/day for 6 weeks) the present data suggest that delta MFMO X CH3 might be effective in a shorter regimen and at lower doses.

01 Nov 1986·The American Journal of Tropical Medicine and HygieneQ4 · MEDICINE

Inhibition of Polyamine Biosynthesis by α-Difluoromethylornithine in African Trypanosomes and Pneumocystis carinii as a Basis of Chemotherapy: Biochemical and Clinical Aspects

Q4 · MEDICINE

Article

Author: Walzer, Peter D. ; Sjoerdsma, Albert ; Bacchi, Cyrus J. ; Schecter, Paul J. ; McCann, Peter P. ; Clarkson, Allen B. ; Barlow, John L. R. ; Bey, Philippe

The symposium provided dramatic evidence of the value of the use of polyamine inhibition via alpha-difluoromethylornithine (DFMO, eflornithine) for advances in chemotherapy of Trypanosoma brucei gambiense sleeping sickness and Pneumocystis carinii pneumonia in acquired immune deficiency syndrome (AIDS) and also for further understanding the metabolic importance of the ubiquitous polyamines in these organisms.

100 Deals associated with Merrell Dow Research Institutes

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100 Translational Medicine associated with Merrell Dow Research Institutes

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Pipeline

Pipeline Snapshot as of 23 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

2

1

Other

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Camiglibose ( α-glucosidase )	Diabetes Mellitus More	Preclinical
Suritozole ( GABAA receptor )	Depressive Disorder More	Preclinical
MDL-28050	Thrombosis More	Discontinued