CLK
CLKs (Cdc2-like kinases) belong to the dual-specificity protein kinase family and regulate transcript splicing through phosphorylation of SR proteins[1]. Mechanistically, CLK activity supports spliceosome molecular machinery and alternative pre-mRNA splicing, processes linked to cancer, neurodegeneration, inflammation, viral replication, and Duchenne muscular dystrophy[1]. In cellular models, CLK inhibitors reduce phosphorylated SR proteins, alter pre-mRNA splicing, suppress cancer cell growth, and induce apoptosis[2]. Compared with related isoforms, CLK1-CLK4 share splicing-control functions, but inhibitor selectivity remains difficult, especially because many CLK1 inhibitors also target CLK4, DYRK kinases, or haspin[3]. Structural studies show that CX-4945 inhibits CLK1, CLK2, and CLK3, with the strongest inhibitory effect on CLK2, supporting isoform-aware inhibitor design[4]. For experimental applications, TG003 suppresses CLK-mediated phosphorylation, SR-protein phosphorylation, nuclear-speckle dissociation, and CLK1-dependent alternative splicing in mammalian cells[5].
Referencias:
- [1]. Song M, et al. Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases. Signal Transduct Target Ther. 2023 Apr 7;8(1):148. [Content Brief]
- [2]. Araki S, et al. Inhibitors of CLK protein kinases suppress cell growth and induce apoptosis by modulating pre-mRNA splicing. PLoS One. 2015 Jan 12;10(1):e0116929. [Content Brief]
- [3]. ElHady AK, et al. An overview of cdc2-like kinase 1 (Clk1) inhibitors and their therapeutic indications. Med Res Rev. 2023 Mar;43(2):343-398. [Content Brief]
- [4]. Lee JY, et al. Structural Basis for the Selective Inhibition of Cdc2-Like Kinases by CX-4945. Biomed Res Int. 2019 Aug 18;2019:6125068. [Content Brief]
- [5]. Muraki M, et al. Manipulation of alternative splicing by a newly developed inhibitor of Clks. J Biol Chem. 2004 Jun 4;279(23):24246-54. [Content Brief]
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Productos relacionados con CLK (31)
Productos relacionados con (31)
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DYRK2-IN-2
0 ImagesReferencia número: HY-402805No. CAS: 2416195-65-6DYRK2-IN-2 (Compound C17) is a selective inhibitor of DYRK2, with its IC50 value being 40.3 nM. The inhibitory activity of DYRK2-IN-2 on DYRK1A (IC50 = 1842 nM), DYRK1B (IC50 = 1335 nM), DYRK4 (IC50 = 1931 nM), DYRK3 (IC50 = 112 nM), and CLKs (IC50 = 540-6496 NM) is relatively low. DYRK2-IN-2 inhibits the phosphorylation of Tau protein at Thr212 and shows moderate cytotoxicity in HT22 cells. DYRK2-IN-2 can be used in cancer research.
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AO-365/43472821
0 ImagesAO-365/43472821 is a selective, brain-penetrant Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitor (IC50 = 0.29 μM) and shows a significant inhibitory effect on (CDC-like kinase 1) CLK1 (IC50 = 0.08 μM). AO-365/43472821 could protect the human neuroblastoma cell line SH-SY5Y from Okadaic acid (HY-N6785) (OA)-induced injury. AO-365/43472821 decreased tau (pSer396)/tau and Aβ1-42 protein expression. AO-365/43472821 can be used for the study of Alzheimer's disease.
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(R)-(+)-O-Demethylbuchenavianine
0 Images(R)-(+)-O-Demethylbuchenavianine is an inhibitor for Cyclin-dependent kinases (CDK). (R)-(+)-O-Demethylbuchenavianine inhibits CDK1, CDK5, glycogen synthase kinase-3 (GSK3), cdc2-like kinase (CLK1) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), with IC50s of 1.1, 0.95, >10, >10 and >10 μM, respectively.
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Haspin-IN-2
0 ImagesReferencia número: HY-146587No. CAS: 2768474-47-9
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CLK1/4-IN-1
0 ImagesReferencia número: HY-146335No. CAS: 3029431-90-8CLK1/4-IN-1 (compound 31) is a potent and selective Clk1 and Clk4 inhibitor with an IC50 value of 9.7 nM and 6.6 nM, respectively. CLK1/4-IN-1 has growth inhibitory activities against T24 cancer cells with GI50 of 1.1 μM. CLK1/4-IN-1 can be used for researching anticancer.
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Indazole 1
0 ImagesReferencia número: HY-125201No. CAS: 2252153-37-8Indazole 1 is a potent CDC2-like kinase 2 (CLK2) inhibitor (IC50=12.3 nM). Indazole 1 inhibits the phosphorylation of SR proteins (e.g., SRSF1, SRSF3) and modulates alternative splicing of Wnt signaling-related genes. Indazole 1 is promising for research of osteoarthritis.
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GSK3-IN-10
0 ImagesReferencia número: HY-172198No. CAS: 844441-56-1GSK3-IN-10 (Compound 4) is a multi-target inhibitor, that mainly targets GSK3α and GSK3β with IC50 of 1.0 nM and 2.0 nM. GSK3-IN-10 inhibits the activation of β-catenin, promotes the neuronal survival, and exhibits a protective effect against endoplasmic reticulum stress.
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CLK1/2-IN-3
0 ImagesReferencia número: HY-113831No. CAS: 1005784-60-0LK1/2-IN-3 (compound 3) is a potent and selective CLK1 and CLK2 inhibitor with IC50 values of 1.1, 2.1, 130, 260, 260 nM for CLK1, CLK2, SRPK1, SRPK2, SRPK3, respectively. CLK1/2-IN-3 shows anti-proliferative activity. CLK1/2-IN-3 reduces the levels of endogenous phosphorylated SR proteins and increases the expression of S6K mRNAs.
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Haspin-IN-1
0 ImagesReferencia número: HY-146586No. CAS: 2768474-30-0
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