FPFT-2216, a “molecular glue” compound, degrades phosphodiesterase 6D (PDE6D), zinc finger transcription factors Ikaros (IKZF1), Aiolos (IKZF3), and casein kinase 1α (CK1α). FPFT-2216 can be used for the research of cancer and inflammatory disease[1][2].
IC50 & Target[1]
PDE6D
CK1α
IKZF1
IKZF3
体外研究 (In Vitro)
FPFT-2216 (1 μM; 5 hours) is able to degrade PDE6D, in addition to its known targets IKZF1, IKZF3, and CK1α in MOLT4 cells[1]. FPFT-2216 (1 μM; 0 h, 2 h, 4 h, 6 h, 16 h, 24 h) shows complete degradation of PDE6D within 2 h, and the degradation of PDE6D persists for at least 24 h in MOLT4 cells[1]. FPFT-2216 (0 nM, 1.6 nM, 8 nM, 40 nM, 200 nM, 1 μM; 4 h) exhibits over 50% degradation of PDE6D at a dose of 8 nM, while maximum degradation of PDE6D along with IKZF1, IKZF3, and CK1α at a dose of 200 nM in MOLT4 cells[1]. FPFT-2216 does not impede the growth of KRASG12C-dependent MIA PaCa-2 cells[1]. FPFT-2216 (10, 20, 40 µM; 14 or 24 h) highly up-regulates the production of IL-2 although it is less potent than that of Pomalidomide in Naive CD4+ T cells[2]. FPFT-2216 (10 µM; 14 or 24 h) degrades IKZF1 and CK-1α among ubiquitin–proteasomal degradative substrates of immunomodulatory drugs (IMiDs) in Naive CD4+ T cells[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
MOLT4 cells
Concentration:
1 μM
Incubation Time:
0 h, 2 h, 4 h, 6 h, 16 h, 24 h
Result:
Showed complete degradation of PDE6D within 2 h, and the degradation of PDE6D persisted for at least 24 h.
Western Blot Analysis[1]
Cell Line:
MOLT4 cells
Concentration:
0 nM, 1.6 nM, 8 nM, 40 nM, 200 nM, 1 μM
Incubation Time:
4 h
Result:
Exhibited over 50% degradation of PDE6D at a dose of 8 nM, while maximum degradation of PDE6D along with IKZF1, IKZF3, and CK1α at a dose of 200 nM.
体内研究 (In Vivo)
FPFT-2216 (30 mg/kg; p.o. or i.p.) induces significant degradation of CK-1α, and IKZF1 in CRBNI391V mice[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
CRBNI391V mice[2]
Dosage:
30 mg/kg (solubilized in 0.5% carboxymethylcellulose/sodium and 0.25% Tween 80)
Administration:
p.o. or i.p.
Result:
Induced significant degradation of CK-1α, and IKZF1.
分子量
292.31
Formula
C12H12N4O3S
CAS 号
2367619-87-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Teng M, et al. Development of PDE6D and CK1α Degraders through Chemical Derivatization of FPFT-2216. J Med Chem. 2022 Jan 13;65(1):747-756.
[2]. Gemechu Y, et al. Humanized cereblon mice revealed two distinct therapeutic pathways of immunomodulatory drugs. Proc Natl Acad Sci U S A. 2018;115(46):11802-11807.
