(S)-2-chloro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-6-carboxamide

Modify Date: 2024-01-08 17:04:48

(S)-2-chloro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-6-carboxamide Structure
(S)-2-chloro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-6-carboxamide structure
Common Name (S)-2-chloro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-6-carboxamide
CAS Number 848193-72-6 Molecular Weight 262.73500
Density N/A Boiling Point N/A
Molecular Formula C14H15ClN2O Melting Point N/A
MSDS Chinese USA Flash Point N/A
Symbol GHS06
GHS06
Signal Word Danger

 Use of (S)-2-chloro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-6-carboxamide


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].

 Names

Name (6S)-2-chloro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-6-carboxamide
Synonym More Synonyms

  Biological Activity

Description 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].
Related Catalog
Target

SIRT1:0.124 μM (IC50)

SIRT2:2.8 μM (IC50)

SIRT3:>100 μM (IC50)

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].
References

[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

[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.

 Chemical & Physical Properties

Molecular Formula C14H15ClN2O
Molecular Weight 262.73500
Exact Mass 262.08700
PSA 59.87000
LogP 4.26630
Storage condition 2-8°C

 Safety Information

Symbol GHS06
GHS06
Signal Word Danger
Hazard Statements H301-H315-H319-H335
Precautionary Statements P261-P301 + P310-P305 + P351 + P338
Personal Protective Equipment dust mask type N95 (US);Eyeshields;Faceshields;Gloves
RIDADR UN 2811 6.1 / PGIII

 Synonyms

chic-35
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