CLK
he CDC-like protein kinases are a widespread family of splice factor kinases involved in normal physiology and in several diseases including cancer. In humans they include the CLK1, CLK2, CLK3 and CLK4 genes. The expression of CLK1 is regulated through alternative splicing producing both full-length catalytically active and truncated catalytically inactive isoforms, CLKT1 (arising from exon 4 skipping) and CLKT2 (arising from intron 4 retention). CLK kinases phosphorylate the so-called ‘SR protein’ splice factors, facilitating their activation and release from nuclear speckles. CLK kinases can also phosphorylate non-SR protein splice factors including the spliceosome-associated SPF45. CLK activity is increasingly associated with the development and progression of cancer. As a result there is considerable interest in developing selective CLK inhibitors that block tumour growth. CLK1 is also a potential target in the treatment of Alzheimer's and has been earmarked for the treatment of Duchenne's muscular dystrophy as its inhibition causes the skipping of a mutated exon. CLK targeting has also been proposed for the treatment of viral infection including HIV-1 and influenza.
References
1.Dale P Corkery,et al. Nucleus. 2015; 6(4): 279–288.
References
1.Dale P Corkery,et al. Nucleus. 2015; 6(4): 279–288.
Cell Cycle/DNA Damage
ABC(12)
AChR(104)
Antifolate(12)
ATM/ATR(26)
Aurora Kinase(51)
CLK(15)
c-Myc(22)
DHFR(16)
DNA Alkylator(34)
DNA gyrase(11)
DNA Repair Protein(21)
DNA/RNA Synthesis(187)
DNA-PK(15)
GPR(97)
HDAC(152)
Hec1/Nek2(9)
Integrin(77)
LIM Kinase (LIMK)(7)
Mps1/TTK(2)
Nucleoside Antimetabolite/Analog(48)
Other Targets(4)
PARP(67)
PLK(26)
Potassium Channel(146)
RAD51(1)
Rho(16)
ROCK(42)
Telomerase(12)
Topoisomerase(88)
Wee1(7)
CLK
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KuWal151
catalog no : M16943
cas no: ——
KuWal151 is a potent, selective cdc2-like kinase (CLK) inhibitor with IC50 of 88/510/28 nM for CLK1/2/4, respectively. -
T-025
catalog no : M16935
cas no: ——
T-025 (T025, CLK inhibitor T-025) is an orally available, potent inhibitor of Cdc2-like kinases (CLKs) with Kd of 4.8, 0.096, 6.5, and 0.61 nM for CLK1, CLK2, CLK3, and CLK4, also inhibits DYRK1A and DYRK1B with IC50 of 0.074 and 1.5 nM. -
CLK2 inhibitor Indazole1
catalog no : M16934
cas no: ——
CLK2 inhibitor Indazole1 is a novel potent, selective inhibitor of CLK2 with IC50 of 2.7 nM. -
TG693
catalog no : M16408
cas no: 885272-55-9
TG693 is an orally available, selective, ATP-competitive CLK1 inhibitor with IC50 of 112.6 nM. -
K00546
catalog no : M14518
cas no: 443798-47-8
K00546 is a potent inhibitor of the CDC2-like kinase CLK1 and CLK3 with IC50 of 8.9 and 29.2 nM, respectively.