PLK
Genetic screens led to the discovery of the first PLKs, Cdc5 and Polo, in budding yeast and Drosophila melanogaster, respectively. PLKs are involved at multiple stages during mitosis and meiosis. PLKs are present in all branches of the Eukarya, and that vertebrates have five paralogues: the Ser/Thr protein kinases PLK1–5. These motifs can be organized in different configurations to regulate PLK activity, localization and function. The ancestral member of the family is PLK1; at least three duplication events gave rise to PLK2–5. All PLKs share similar architecture: they have an amino-terminal (Ser/Thr) catalytic kinase domain and a carboxy-terminal region containing two or more PBs, which are organized in different domains. PLK1–3 have very similar catalytic domains, whereas that of PLK4 has a divergent primary sequence, and PLK5 includes a pseudokinase domain. PLK1 target proteins are usually ‘primed’ through phosphorylation by a Pro-directed kinase, such as cyclin-dependent kinase 1 (CDK1) and MAPKs, for optimal binding to PLK1.
PLK1 inactivates the G2 DNA damage checkpoint in different ways: it phosphorylates claspin, which targets it for degradation and leads to the inactivation of Ser/Thr protein kinase CHK1 and ATR; it phosphorylates tumour suppressor p53-binding protein 1 (p53BP1), which promotes p53BP1 dissociation from DNA and inactivation of CHK2, rendering it unable to bind to its ligands. PLK1 also participates in DNA damage repair through phosphorylation of DNA repair protein RAD51 homologue 1 (RAD51), which results in p53BP1 accumulation at the sites of damage. PLK2 and PLK4 control centriole duplication. PLK3 is required for G1/S transition, promotes DNA replication, and might also have a role in mitotic progression. In contrast to PLK1 and PLK4, the other three members PLK2, PLK3 and PLK5 are mostly found in non-proliferative tissues, in which they are involved in cell differentiation and, in the case of PLK2 and PLK5, in neuronal activity. Interestingly, PLK2 regulates mitotic spindle orientation in the mammary gland and is required for its development. PLK3 has also been ascribed various functions, such as in programmed cell death148, in the hypoxia signalling pathway, in oxidative and hyperosmotic stress responses, and in the regulation of Golgi fragmentation during the cell cycle. The importance of PLKs in key cell cycle processes is apparent, as the perturbation of these kinases causes multiple diseases.
PLK1 inactivates the G2 DNA damage checkpoint in different ways: it phosphorylates claspin, which targets it for degradation and leads to the inactivation of Ser/Thr protein kinase CHK1 and ATR; it phosphorylates tumour suppressor p53-binding protein 1 (p53BP1), which promotes p53BP1 dissociation from DNA and inactivation of CHK2, rendering it unable to bind to its ligands. PLK1 also participates in DNA damage repair through phosphorylation of DNA repair protein RAD51 homologue 1 (RAD51), which results in p53BP1 accumulation at the sites of damage. PLK2 and PLK4 control centriole duplication. PLK3 is required for G1/S transition, promotes DNA replication, and might also have a role in mitotic progression. In contrast to PLK1 and PLK4, the other three members PLK2, PLK3 and PLK5 are mostly found in non-proliferative tissues, in which they are involved in cell differentiation and, in the case of PLK2 and PLK5, in neuronal activity. Interestingly, PLK2 regulates mitotic spindle orientation in the mammary gland and is required for its development. PLK3 has also been ascribed various functions, such as in programmed cell death148, in the hypoxia signalling pathway, in oxidative and hyperosmotic stress responses, and in the regulation of Golgi fragmentation during the cell cycle. The importance of PLKs in key cell cycle processes is apparent, as the perturbation of these kinases causes multiple diseases.
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)
PAK(13)
PARP(67)
PLK(26)
Potassium Channel(146)
RAD51(1)
Rho(16)
ROCK(42)
Telomerase(12)
Topoisomerase(88)
Wee1(7)
PLK
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Dihydrobaicalein
产品货号 : M37769
cas no: 35683-17-1
DiHydrobaicalein 是一种 PLK1 抑制剂,IC50 为 6.3 μM。DiHydrobaicalein 还抑制 VRK2 和 PLK2。DiHydrobaicalein 是一种可以从黄芩中分离得到的天然产物。 -
Plogosertib
产品货号 : M36368
cas no: 1137212-79-3
Plogosertib (CYC140) 是一种选择性的、有效的、具有口服活性的 ATP 竞争性的 PLK1 抑制剂 (IC50: 3 nM)。Plogosertib 是一种有抗增殖活性的抗癌剂,可用于多种肿瘤的研究,包括食管癌、胃癌、白血病、非小细胞肺癌、卵巢癌和鳞状细胞癌。 -
T521
产品货号 : M34437
cas no: 891020-54-5
T521 is a selective inhibitor of the PBD of Plk1 and shows no inhibitory effect on Plk2 and Plk3. -
Poloxin-2
产品货号 : M34116
cas no: 321695-37-8
Poloxin-2 is a potent and selective Plk1 PBD inhibitor with anti-tumour activity that reduces the protein level of Plk1 in HeLa cells. -
Cyclapolin 9
产品货号 : M33843
cas no: 40533-25-3
Cyclapolin 9 是一种有效的,选择性的和 ATP 竞争性 polo-like kinase 1 (PLK1) 抑制剂,IC50 为 500 nM,对其他激酶没有活性。