DesignMedix Technology and Publications: a unique rapid approach for developing drugs to overcome drug resistance.

DesignMedix, Inc. has a unique, rapid approach for developing drugs to overcome drug resistance. This platform approach is a way of making novel compounds by covalently linking a chemical moiety derived from a resistance reversal agent to a drug that has had strong resistance evolve against it, thereby creating a new drug that can fulfill both roles - drug and resistance reversal. This approach enables the design and synthesis of novel drugs very rapidly to enter the optimization stage of development far sooner than widely-used screening approaches. Development risk is reduced because the approach leverages the safety and efficacy properties of the original drug.

Technology

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Targeting drug-resistant diseases with dual-action drugs

Novel patentable drugs are created with the ability to reverse drug-resistance. The molecules created may have dual or multiple actions that confer efficacy by a known mode of action as well as reversal of drug resistance. The mechanism of drug resistance has been demonstrated for the anti-malarial drugs.

Andrews S, Burgess SJ, Skaalrud D, Kelly JX, Peyton DH: Reversal agent and linker variants of reversed chloroquines: activities against Plasmodium falciparum. J. Med. Chem. 2010, 53(2):916-919.

Burgess SJ, Selzer A, Kelly JX, Smilkstein MJ, Riscoe MK, Peyton DH: A Chloroquine-like Molecule Designed to Reverse Resistance in Plasmodium falciparum. J. Med. Chem. 2006, 49(18):5623-5625.

Kelly, JX, Smilkstein, MJ, Brun, R, Wittlin, S, Cooper, RA, Lane, KD, Janowsky, A, Johnson, RA, Dodean, RA, Winter, R, Hinrichs, DJ, Riscoe, MK: Discovery of dual function acridones as a new antimalarial chemotype. Nature 2009, 459: 270-273.

Kelly, JX, Smilktein, M, Cooper, RA, Lane, KD, Johnson, RA, Janowsky, A, Dodean, RA, Hinrichs, DJ, Winter, RW, Riscoe, MK: Design, synthesis, and evaluation of 10-N-substituted acridones as novel chemosensitizers in Plasmodium falciparum. Antimicrob Agents Chemother 2007, 51(11), 4133-4140.

Smilkstein, M, Sriwilaijaroen, N, Kelly JX, Wilairat P, Riscoe, MK: Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening. Antimicrob Agents Chemother 2004, 48,1803-1806.

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