cGAS PROTAC TH35

Chemical Structure : cGAS PROTAC TH35

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货号: PC-24090Not For Human Use, Lab Use Only.

cGAS PROTAC TH35 is an effective, selective CRBN-recruiting cGAS-targeting PROTAC degrader with DC50 of 0.9 uM and 4.6 uM in THP-1 and RAW 264.7 cells respectively, Dmax >90% at 20 uM.

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100 mg		Get quote

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生物&药学活性

cGAS PROTAC TH35 is an effective, selective CRBN-recruiting cGAS-targeting PROTAC degrader with DC50 of 0.9 uM and 4.6 uM in THP-1 and RAW 264.7 cells respectively, Dmax >90% at 20 uM.
TH35 inhibits dsDNA-induced cGAS activation in both THP1-Lucia ISG and RAW-Lucia ISG cells, with IC50 values of 1.8 and 4.8 uM respectively.
TH35 efficiently induces degradation of both human cGAS (h-cGAS) and murine cGAS (m-cGAS).
TH35 effectively induces cGAS degradation mediated by the ubiquitin–proteasome pathway in a CRBN-dependent manner.
TH35 specifically targets cGAS to inhibit the expression of interferon regulatory factor (IRF)-inducible genes rather than acting on downstream proteins of the cGAS-STING pathway.
TH35 dose-dependently inhibits the phosphorylation of STING, TBK1 and IRF3 in both THP-1 and RAW 264.7 cells.
TH35 suppresses the mRNA expression of IFNB in response to dsDNA, including 45-bp immune stimulatory DNA (ISD), herpes simplex virus-1 (HSV-1), and HT-DNA, in THP-1 cells.
TH35 (20 and 50 mg/kg, i.p.) ameliorates DSS-induced colitis in mouse model of DSS-induced ulcerative colitis (UC), alleviates cGAS-mediated inflammation responses in vivo.

物理化学性质&存储条件

分子量	714.60
分子式	C36H33Cl2N7O5
外观性状	Solid
CAS No.
储存条件	固体粉末 -20°C 12 个月; 4°C 6 个月	配置液 -80°C 6 个月; -20°C 6 个月
Shipping
Solubility	10 mM in DMSO
Chemical Name/SMILES	N-(2-(6,7-Dichloro-9-(1-methyl-1H-pyrazol-3-yl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)-2-oxoethyl)-6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-ynamide

参考文献

1. He P, et al. J Med Chem. 2025 Feb 26. doi: 10.1021/acs.jmedchem.4c02774.

cGAS PROTAC TH35

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cGAS PROTAC TH35

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