ChemicalBook CAS DataBase List 2449301-27-1

2449301-27-1

Name	1H-Indole-3-carbonitrile, 2-amino-6-[2-(3-fluorophenyl)ethenyl]-
CAS	2449301-27-1
Molecular Formula	C17H12FN3
Molecular Weight	277.3
MOL File	2449301-27-1.mol

Chemical Properties

Boiling point	540.4±50.0 °C(Predicted)
density	1.33±0.1 g/cm3(Predicted)
solubility	DMSO:90.0(Max Conc. mg/mL);324.56(Max Conc. mM) Ethanol:8.0(Max Conc. mg/mL);28.85(Max Conc. mM)
form	Solid
pka	16.49±0.30(Predicted)
color	Light yellow to yellow

Hazard Information

Uses

GSK2643943A is a deubiquitinating enzyme (DUB) inhibitor targeting USP20. GSK2643943A has affinity with an IC50 of 160 nM for USP20/Ub-Rho. GSK2643943A has anti-tumor efficacy and can be used for the research of oral squamous cell carcinoma (OSCC) [1][2].

in vivo

GSK2643943A (5 mg/kg, i.p., daily, for 6 days) potentiates oHSV-1-induced oncolysis in SCC9 tumors^[2].
? GSK2643943A (2.5 mg/kg, i.p., daily, for 9 days) plays a regulatory role in oHSV-1 T1012G replication and oncolysis in SCC7 cells^[2].

Animal Model:	The subcutaneous xenograft model^[2]. (SCC9 or SCC7 cells (8×10⁶ cells or 1×10⁶ cells), 5-week-old, female, BALB/c nude mice or C3H/HeN mice, four groups, n = 6-7, per group)^[2]
Dosage:	5 mg/kg
Administration:	GSK2643943A (alone): intraperitoneal administration, daily, for 6 days. GSK2643943A (combination): intraperitoneal administration, daily for 6 days + intratumoral injection with 50 mL of 1×10⁶ PFU T1012G in PBS on day 1, day 4, and day 7.
Result:	Caused a visible drop of tumor volumes and significantly reduced the tumor volumes in mice with combined treatment of GSK2643943A and oHSV-1 T1012G. Increased slightly viral ICP0 and gD mRNA accumulation in SCC9 tumors.

Animal Model:	The SCC7 mouse model^[2].
Dosage:	2.5 mg/kg
Administration:	GSK2643943A (alone): intraperitoneal administration, daily, for 9 days. GSK2643943A (combination): intraperitoneal administration, daily, for 9 days + intratumoral injection, with 50 mL of 1×10⁷ PFU T1012G in PBS on days 1, 4, 7, and 10.
Result:	Caused a visible drop of tumor volumes, significantly reduced in mice with combined treatment of GSK and oHSV-1 T1012G. Increased slightly viral ICP0 and gD mRNA accumulation in SCC7 tumors.

References

[1] Nishi Kumari, et al. Targeting the Ubiquitin Proteasome System in Cancer. Shahzad, Hafiz Naveed (2018). Neoplasm Targeting the Ubiquitin Proteasome System in Cancer. , 10.5772/intechopen.69560(Chapter 8).
[2] Ruitao Lu, et al. USP18 and USP20 restrict oHSV-1 replication in resistant human oral squamous carcinoma cell line SCC9 and affect the viability of SCC9 cells. Mol Ther Oncolytics. 2021 Nov 11;23:477-487. DOI:10.1016/j.omto.2021.11.004

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