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]. In Vitro: 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].