CHIC35 

CHIC35, an analog of EX-527, is a potent and selective inhibitor of SIRT1 (IC₅₀=0.124 µM). CHIC35 shows potential selective inhibition against SIRT1 over SIRT2 (IC₅₀=2.8 µM) or SIRT3 (IC₅₀>100 µM)^[1]. CHIC35 has anti-inflammatory effects and can be used for CHARGE syndrome research^[1][2].

CHIC-35 (0.5 μM; 16 hours) increases acetylation of histone H4 in BMDMs similar to Cambinol (200 μM)^[1].
CHIC-35 (5 μM; 72 hours) exhibits no significant difference in the survival of embryos at early stages^[2].
Zebrafish embryos are microinjected with 2.4 ng of chd7 MO to develop to different stages of development. chd7 morphant embryos are treated with CHIC-35 from 8hpf to 24hpf. CHIC-35 (5 μM) is removed at 24hpf and embryos are incubated in fresh egg water until 4dpf. The chd7 morphant larvae has a severely reduced and disrupted pattern of cartilage elements in comparison to the control, CHIC-35 shows partial recovery in craniofacial cartilage elements^[2].
At 4dpf, zebrafish embryos show a well-formed lower jaw in controls, while chd7 morphants exhibits reduced lower jaw. Treatment with CHIC-35 (5 μM) rescues the expression of sox9a inchd7 morphants^[2].
Nearly 30% of chd7 morphant embryos (24hpf to 72hpf) shows a near complete loss of isl2a expression in the cranial region compared to 10% of the wildtype controls. CHIC-35 reduces this to 7.5% significantly. However, CHIC-35 shows no discernible effect on the enteric neurons marked by Tg^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

262.73

C₁₄H₁₅ClN₂O

848193-72-6

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• [1]. Jérôme Lugrin, et al. The sirtuin inhibitor cambinol impairs MAPK signaling, inhibits inflammatory and innate immune responses and protects from septic shock. Biochim Biophys Acta. 2013 Jun;1833(6):1498-510  [Content Brief]

  [2]. Zainab Asad, et al. Chemical screens in a zebrafish model of CHARGE syndrome identifies small molecules that ameliorate disease-like phenotypes in embryo. Eur J Med Genet. 2020 Feb;63(2):103661.  [Content Brief]