Iclaprim

Source: Wikipedia, the free encyclopedia.
Iclaprim
Clinical data
Routes of
administration		intravenous
ATC code
Legal status
Legal status
  • Investigational
Identifiers
  • (RS)-5-[(2-Cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl)methyl]pyrimidine-2,4-diamine
JSmol)
ChiralityRacemic mixture
  • COC1=C(C2=C(C=CC(O2)C3CC3)C(=C1)CC4=CN=C(N=C4N)N)OC
  • InChI=1S/C19H22N4O3/c1-24-15-8-11(7-12-9-22-19(21)23-18(12)20)13-5-6-14(10-3-4-10)26-16(13)17(15)25-2/h5-6,8-10,14H,3-4,7H2,1-2H3,(H4,20,21,22,23) ☒N
  • Key:HWJPWWYTGBZDEG-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Iclaprim is an

Gram positive organisms.[1][2] It is administered intravenously.[3]
: 3 

In vitro, iclaprim is active against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA), strains of Streptococcus pneumoniae resistant to several common antibiotics, and some Gram-negative bacteria.[4] It is of the diaminopyrimidine dihydrofolate reductase (DHFR)-inhibiting type.

History

Iclaprim is an optimized analog of

Roche.[5] Arpida was spun out of Roche in 1998,[5][6] and acquired iclaprim from Roche in 2001.[7]: 77  Arpida held an initial public offering on the Swiss stock exchange in 2005.[8]

Arpida ran two

new drug application was filed with the United States Food and Drug Administration based on these trials, and was rejected due to failure to show non-inferiority and due to safety concerns, especially drug-induced QT prolongation.[2][9] The FDA advisory committee said that the drug "should not be developed further" based on the results presented.[10] A parallel application for marketing approval to the European Medicines Agency was withdrawn in 2009; in the announcement of the withdrawal, the EMA said that there was insufficient data from clinical studies to justify the dosage proposed by the company and that resistance to the drug had already been seen in the clinical trial data.[11]

Arpida collapsed after the rejection by the FDA and the EMA withdrawal.

reverse merger in September 2009.[12] Arpida sold off iclaprim to Acino Pharma in November 2009,[13] and in December 2009, Arpida and Evolva completed their transaction.[14]

Acino sold the rights to iclaprim, its data and regulatory filings, and manufactured drug to a group called Life Sciences Management Group of

qualified infectious disease product status for iclaprim.[10]

In September 2017, the FDA granted orphan drug status to iclaprim for the treatment of Staphylococcus aureus lung infections in people with cystic fibrosis.[16] Iclaprim was non-inferior to vancomycin when it was studied in two phase III studies of acute skin and skin structure infections published in 2018.[17][18] As of February 2019, it is still not approved.

Chemistry

Iclaprim contains a stereocenter and is a

racemate, a 1: 1 mixture of (R)- and (S)-enantiomers
:

Enantiomers of iclaprim

CAS number: 1208116-65-7
CAS number: 1208116-66-8

Names

During its development, other names for the drug have included AR-100, MTF-100, RO-48-2622,[19] and the brand name Mersarex.[11] It received its INN name in 2003.[20]

References

  1. PMID 19917023
    .
  2. ^
    PMID 28642145
    .
  3. ^ "Iclaprim for the Treatment of Complicated Skin and Skin Structure Infections" (PDF). FDA. November 20, 2008.
  4. S2CID 219289697
    .
  5. ^ a b Firn D (11 October 2004). "Arpida takes advice on stock market flotation". Financial Times.
  6. ^
    PMID 21233508
    .
  7. ^ a b c "Form F-1". Motif Bio plc via SEC Edgar. July 12, 2016.
  8. ^ Thompson V (April 12, 2005). "Roche spin-off plans float to fund drug trials". SWI swissinfo.ch.
  9. ^ "Summary Minutes of the Anti-Infective Drugs Advisory Committee November 18-20, 2008" (PDF). US Food and Drug Administration.. "Iclaprim for the Treatment of Complicated Skin and Skin Structure Infections FDA Briefing Document for Anti-Infective Drugs Advisory Committee Meeting" (PDF). US Food and Drug Administration. 20 November 2008.
  10. ^ a b King A (3 August 2015). "FDA veteran questions science behind antibiotics fast track". In-PharmaTechnologist.
  11. ^ a b "Questions and answers on the withdrawal of the marketing authorisation application for Mersarex (iclaprim)" (PDF). EMA. 19 November 2009.
  12. ^ "Privately owned Evolva takes over biotech Arpida". Reuters. September 10, 2009.
  13. ^ "Press Release: Acino Acquires Iclaprim Activities from Arpida". Acino, Roche, Arpida via Evaluate Group. November 4, 2009.
  14. ^ "Press Release: Evolva SA Completes Merger With Arpida Ltd". Evolva Holding, Novartis, Arpida via Evaluate Group. December 14, 2009.
  15. ^ "Press release: Motif Bio Announces Intention to Float on AIM". Motif Bio plc. February 2, 2015. Archived from the original on 17 March 2016.
  16. ^ "Iclaprim Orphan Drug Designation". FDA. Retrieved 16 September 2017.
  17. PMID 29281036
    .
  18. PMID 29530858
    .
  19. ^ "Iclaprim". AdisInsight. Springer Nature Switzerland AG. Retrieved 13 September 2017.
  20. ^ "Recommended INN List 50" (PDF). WHO Drug Information. 17 (4). 2003.

External links

Further reading

  • Schneider P, Hawser S, Islam K (December 2003). "Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria". Bioorganic & Medicinal Chemistry Letters. 13 (23): 4217–4221.
    PMID 14623005
    .
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