CDK5
CDK5 is a proline-directed serine/threonine kinase that controls neuronal development, postsynaptic signal integration, neurotransmitter release, and neurite outgrowth[1][2]. Mechanistically, CDK5 activity depends on neural activators such as p35, and p35-deficient mice show cortical lamination defects, seizures, and adult lethality[3][4]. In disease models, calpain-mediated conversion of p35 to p25 deregulates CDK5 activity and promotes neurodegeneration, linking the CDK5-p25 axis to tau phosphorylation research[5]. Compared with proliferative CDKs, CDK5 differs because p35 or p39 binding activates it, whereas Tyr-15 phosphorylation does not activate the CDK5-p35 complex[6]. For experimental applications, roscovitine inhibits cdc2, CDK2, and CDK5, while p35-derived peptides specifically inhibit deregulated CDK5 activity[7][8].
References:
- [1]. Kim SH, et al. CDK5 serves as a major control point in neurotransmitter release. Neuron. 2010 Sep 9;67(5):797-809. [Content Brief]
- [2]. Nikolic M, et al. The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation. Genes Dev. 1996 Apr 1;10(7):816-25. [Content Brief]
- [3]. Tsai LH, et al. p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature. 1994 Sep 29;371(6496):419-23. [Content Brief]
- [4]. Chae T, et al. Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron. 1997 Jan;18(1):29-42. [Content Brief]
- [5]. Patrick GN, et al. Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature. 1999 Dec 9;402(6762):615-22. [Content Brief]
- [6]. Kobayashi H, et al. Phosphorylation of cyclin-dependent kinase 5 (Cdk5) at Tyr-15 is inhibited by Cdk5 activators and does not contribute to the activation of Cdk5. J Biol Chem. 2014 Jul 11;289(28):19627-36. [Content Brief]
- [7]. Meijer L, et al. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem. 1997 Jan 15;243(1-2):527-36. [Content Brief]
- [8]. Kesavapany S, et al. Peptides derived from Cdk5 activator p35, specifically inhibit deregulated activity of Cdk5. Biotechnol J. 2007 Aug;2(8):978-87. [Content Brief]
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CDK5 Related Products (97)
Related Products (97)
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Recombinant Proteins (5)
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Antibodies (3)
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(S)-Roscovitine
0 ImagesSynonyms: (S)-Seliciclib; (S)-CYC202(S)-Roscovitine ((S)-Seliciclib; (S)-CYC202) is a potent and cross the blood-brain barrier CDKs inhibitor. (S)-Roscovitine shows neuroprotective efficacy. (S)-Roscovitine has the potential for the research of stroke.
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TMX-2172
0 ImagesTMX-2172 is a selective bivalent cereblon-recruiting PROTAC-based dual CDK2 and CDK5 degrader with IC50 values of 6.5 nM and 6.8 nM, respectively. TMX-2172 shows selectivity for CDK2 and CDK5 over other cell cycle CDKs (CDK1, CDK4, and CDK6) and transcriptional CDKs (CDK7 and CDK9). TMX-2172 inhibits CDK2/CDK5 enzymatic activity, induces their proteasomal degradation, reduces ASCL1 protein levels and half-life, induces cancer cell death, and exerts antiproliferative effects. TMX-2172 can be used for the research of ovarian cancer and small cell lung cancer.
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Manzamine A hydrochloride
0 ImagesSynonyms: Keramamine A hydrochlorideManzamine A hydrochloride, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 μM and 1.5 μM, respectively. Manzamine A hydrochloride targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Manzamine A hydrochloride has antimalarial and anticancer activities. Manzamine A hydrochloride also shows potent activity against HSV-1.
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Samuraciclib hydrochloride hydrate
0 ImagesCat. No.: HY-103712CPurity: 99.80%Synonyms: CT7001 hydrochloride hydrate; ICEC0942 hydrochloride hydrateSamuraciclib (CT7001) hydrochloride hydrate is a potent, selective, ATP-competitive and orally active CDK7 inhibitor, with an IC50 of 41 nM. Samuraciclib hydrochloride hydrate displays 45-, 15-, 230- and 30-fold selectivity over CDK1, CDK2 (IC50 of 578 nM), CDK5 and CDK9, respectively. Samuraciclib hydrochloride hydrate inhibits the growth of breast cancer cell lines with GI50 values between 0.2-0.3 μM. Samuraciclib hydrochloride hydrate has anti-tumor effects.
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7BIO
0 ImagesSynonyms: 7-Bromoindirubin-3-Oxime7BIO (7-Bromoindirubin-3-Oxime) is the derivate of indirubin. 7BIO (7-Bromoindirubin-3-Oxime) has inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β). 7BIO (7-Bromoindirubin-3-Oxime) inhibits Aβ oligomer-induced neuroinflammation, synaptic impairments, tau hyper-phosphorylation, activation of astrocytes and microglia, and attenuates Aβ oligomer-induced cognitive impairments in mice[1].
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GSK-3 inhibitor 3
0 ImagesGSK-3 inhibitor 3 is a selective, orally active and brain-penetrant inhibitor of GSK-3, with IC50s of 0.35 nM and 0.25 nM for GSK-3α and GSK-3β, respectively. GSK-3 inhibitor 3 lowers levels of tau protein phosphorylation at S396 in a triple-transgenic mouse Alzheimer’s disease model, with IC50 of 10 nM. GSK-3 inhibitor 3 can be used for neurological disease research.
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SB1-G-187
0 ImagesSB1-G-187 is a multi-target kinase PROTAC degrader with activity against various kinases including GCK, YES1, IRAK1 and LYN. SB1-G-187 induces degradation of target kinases via a p97-dependent pathway, and forms ternary complexes with CRBN and specific functional kinases. SB1-G-187 can be used in tumor-related research.
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PNU-292137
0 ImagesPNU-292137 is an orally active, potent CDK2 inhibitor with IC50s of 37 nM and 92 nM for CDK2/cyclin A and CDK2/cyclin E, respectively. PNU-292137 makes interactions with the hydrophobic pocket at the back of the CDK2 ATP pocket. PNU-292137 efficiently inhibits tumor cell proliferation in human colon and prostate tumor cell lines. PNU-292137 exhibits antitumor activity (TGI>50%) in a mouse xenograft model.
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AG-012986
0 ImagesAG-012986 is a pan-CDK inhibitor with Ki values of 44 nM (CDK1), 9.2 nM (CDK4), 94 nM (CDK2), and IC50 values of 22 nM (CDK5), 4 nM (CDK9). AG-012986 causes apoptosis of T-cells by targeting upstream kinases in the p38 Mitogen-activated protein kinase (MAPK) pathway and impairing cellular survival. AG-012986 induces cell cycle arrest, retinoblastoma protein hypophosphorylation, and reduces Ki-67 expression. AG-012986 exerts antiproliferative activity in tumor cells, demonstrates antitumor efficacy in human xenograft models, and causes retinal and peripheral neurotoxicity, plus immune cell toxicity. AG-012986 can be used for the research of colon carcinoma, non-small cell lung carcinoma, lung carcinoma, breast carcinoma, ovarian tumor, pancreatic carcinoma, osteosarcoma, lymphoma, leukemia, retinotoxicity.
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NVP-LCQ195
0 ImagesSynonyms: LCQ-195; AT9311NVP-LCQ195 (LCQ-195) is an inhibitor of CDK1/2/3/5/9. NVP-LCQ195 induces cell cycle arrest and eventual apoptotic cell death of multiple myeloma (MM) cells. NVP-LCQ195 triggers decreased amplitude of transcriptional signatures related to oncogenesis, drug resistance and stem cell renewal in MM cell lines.
