AFN-1252

• CAS: 620175-39-5
• Catalog Number: ACM620175395
• Category: Inhibitors
• Molecular Weight: 375.43
• Molecular Formula: C22H21N3O3
• Description: AFN-1252, also known as AFN-12520000; API-1252; Debio-1452, is FASII Inhibitor which is potentially for the treatment of acute bacterial skin. AFN-1252 exhibits typical MIC(90) values of ≤0·015 μg/ml against diverse clinical isolates of S. aureus, oral absorption, long elimination half-live and efficacy in animal models. AFN-1252 efficiently blocked daptomycin-induced phospholipid decoy production, even in the case of isolates resistant to AFN-1252, which prevented the inactivation of daptomycin and resulted in sustained bacterial killing. In turn, daptomycin prevented the fatty acid-dependent emergence of AFN-1252-resistant isolates in vitro
• Synonyms: AFN-1252; AFN 1252; AFN1252; API-1252; API1252; API 1252; AFN12520000; AFN 12520000; AFN12520000; Debio1452; Debio 1452; Debio1452
• IUPAC Name: (E)-N-methyl-N-((3-methylbenzofuran-2-yl)methyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide
• Canonical SMILES: O=C(N(C)CC1=C(C)C2=CC=CC=C2O1)/C=C/C3=CC(CC4)=C(N=C3)NC4=O
• InChI: InChI=1S/C22H21N3O3/c1-14-17-5-3-4-6-18(17)28-19(14)13-25(2)21(27)10-7-15-11-16-8-9-20(26)24-22(16)23-12-15/h3-7,10-12H,8-9,13H2,1-2H3,(H,23,24,26)/b10-7+
• InChI Key: QXTWSUQCXCWEHF-JXMROGBWSA-N
• Solubility: Soluble in DMSO
• Appearance: White to off-white solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 1047981-31-6 (tosylate); 620175-39-5 (free base); 1047981-30-5 (tosylate hydrate)
• Biological Target: AFN-1252 (Debio 1452) is a potent inhibitor of enoyl-acyl carrier protein reductase (FabI).
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 70.38; H, 5.64; N, 11.19; O, 12.78
• Exact Mass: 375.1583
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: The effect of increasing concentrations of AFN-1252 on the growth rate of L. monocytogenes in planktonic culture was measured to determine the contribution of LmFabI versus LmFabK1 to fatty acid synthesis and growth. AFN-1252 caused the cessation of cell growth after 1 to 2 cellular doublings in bacterial genes encoding a single, essential FabI. In contrast, increasing concentrations of AFN-1252 slowed but did not stop the growth of L. monocytogenes (Fig. 3A). Pathway labeling experiments showed that AFN-1252 selectively inhibited lipid synthesis, with minimal perturbation to protein, DNA, and RNA synthesis (Fig. 3B). Therefore, the reduction of growth rate by AFN-1252 was attributed to on-target inhibition of LmFabI and fatty acid synthesis.; Reference: Infect Immun. 2016 Dec; 84(12): 3597-3607. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116736/
• In Vivo Activity: The first experiments involved administering a single oral dose of AFN-1252 (100 mg/kg) 2 h after infecting the granuloma pouches and examining the effect of AFN-1252 on pouch-associated CFU within 48 h of dosing (Fig. 3A). Little change in the bacterial load was detected within the first 12 h of AFN-1252 treatment, but between 24 and 48 h, there was a 3.0-log10 reduction in the mean CFU/ml of pouch fluid collected from AFN-1252-treated mice compared to untreated mice (Fig. 3A). Wood46 counts in untreated pouch fluid increased to 7.5 log10 CFU/ml at 24 h, while bacterial counts in AFN-1252-treated pouches dropped to 4.4 log10 CFU/ml in 24 h. When 100 mg/kg of AFN-1252 was orally administered once a day for 3 days (+2, +26, and +50 h), AFN-1252 reduced 72-hour S. aureus CFU counts in the pouches of treated animals by 5 orders of magnitude compared to untreated controls, which was near the detection limit for this model (Fig. 3B). These data illustrate that orally administered AFN-1252 can reach therapeutic levels in the mouse granuloma pouch and effectively resolve the S. aureus infection associated with the pouch fluid.; Reference: Antimicrob Agents Chemother. 2013 May; 57(5): 2182-2190. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632907/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).