( RS)-5-[(2- cyclopropyl-7,8-dimethoxy-2 H-chromen-5-yl)methyl]pyrimidine-2,4-diamine
Bioavailability Good (oral)
C 19 H 22 N 4 O 3
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Iclaprim ( INN), codenamed AR-100 and RO-48-2622, is a diaminopyrimidine dihydrofolate reductase (DHFR)- inhibiting extended-spectrum antibiotic active against gram positive organisms being developed for the treatment of complicated skin and soft tissue infections caused by antibiotic-resistant bacteria. It is structurally related to [2 ] trimethoprim. In Phase III clinical trials, intravenously-administered iclaprim was found to be as effective as and better tolerated than linezolid in people with skin and soft tissue infections, many caused by methicillin-resistant (MRSA). Staphylococcus aureus [3 ] [4 ] , iclaprim is highly active against MRSA, In vitro vancomycin-resistant (VRSA), strains of Staphylococcus aureus resistant to several common antibiotics, and some Streptococcus pneumoniae Gram-negative bacteria. [1 ]
new drug application for iclaprim was filed with the U.S. Food and Drug Administration in March 2008, and a marketing authorisation application (MAA) was accepted by the [3 ] European Medicines Agency on August 21, 2008. Phase II clinical trials are being conducted to assess whether iclaprim can be taken by mouth as well as intravenously and whether it is effective for the treatment of hospital-acquired pneumonia. [4 ] [5 ]
Iclaprim was granted
fast track status by the FDA, but approval of the drug was eventually declined in 2009 [6 ] and no further development has taken place since then. [7 ]
Iclaprim & NADPH bound to DHFR.
PDB entry: 3FRA
. The different amino acids are color coded.
References [ edit ]
^ a b Kohlhoff SA, Sharma R (September 2007). "Iclaprim". Expert Opin Investig Drugs 16 (9): 1441–8. doi: 10.1517/135437188.8.131.521. PMID 17714029.
^ Kohlhoff, SA; Sharma, R (September 2007). "Iclaprim.". Expert Opinion on Investigational Drugs 16 (9): 1441–8. doi: 10.1517/135437184.108.40.2061. PMID 17714029.
^ a b "Arpida Submits New Drug Application for Intravenous Iclaprim for Treatment of Skin Infections" (Press release). Reuters. March 19, 2008 . Retrieved . 2008-08-24
^ a b "Arpida's iclaprim MAA Accepted for Review by EMEA" (Press release). PR Newswire. August 21, 2008 . Retrieved . 2008-08-24
^ Peppard, WJ; Schuenke, CD (February 2008). "Iclaprim, a diaminopyrimidine dihydrofolate reductase inhibitor for the potential treatment of antibiotic-resistant staphylococcal infections". Current Opinion on Investigational Drugs 9 (2): 210–25. PMID 18246524.
^ Morgan A, Cofer C, Stevens DL (March 2009). "Iclaprim: a novel dihydrofolate reductase inhibitor for skin and soft tissue infections". Future Microbiol 4 (2): 131–44. doi: 10.2217/174609220.127.116.11. PMID 19257839.
^ Arpida receives FDA complete response letter for Iclaprim
Further reading [ edit ]