135897-06-2 Usage
Description
SB218078 is a potent and selective inhibitor of checkpoint kinase 1 (Chk1), a protein that plays a crucial role in the regulation of cell cycle progression and the maintenance of genomic stability. It works by blocking the phosphorylation of cdc25, an essential step in the activation of cyclin-dependent kinases (CDKs), with an IC50 value of 15 nM. SB218078 also less potently inhibits cdc2 and PKC (IC50s = 250 and 1,000 nM, respectively) and causes 85% inhibition of PKD1 at 1 μM. By releasing G2 cell cycle arrest induced by γ-irradiation or the topoisomerase I inhibitor topotecan, SB218078 enhances the cytotoxicity of DNA-damaging compounds, making it a valuable tool in the study and treatment of various diseases, particularly cancer.
Uses
Used in Cancer Research and Treatment:
SB218078 is used as a research tool for studying the role of Chk1 in the regulation of cell cycle progression and DNA damage response. Its ability to inhibit Chk1 activity makes it a valuable compound for investigating the mechanisms underlying cell cycle arrest and DNA repair processes.
SB218078 is also used as a therapeutic agent in the treatment of cancer. By enhancing the cytotoxicity of DNA-damaging compounds, it can potentially improve the efficacy of chemotherapy and radiotherapy in cancer patients. Its selective inhibition of Chk1 may also help to minimize side effects associated with non-selective inhibitors.
Used in Drug Development:
SB218078 serves as a lead compound in the development of new drugs targeting Chk1 for the treatment of cancer and other diseases. Its potent and selective inhibition of Chk1 makes it an attractive starting point for the design and synthesis of more potent and selective Chk1 inhibitors with improved pharmacological properties.
Used in Drug Delivery Systems:
In order to improve the delivery, bioavailability, and therapeutic outcomes of SB218078, various drug delivery systems have been explored. These systems aim to enhance the efficacy of SB218078 by protecting it from degradation, targeting it specifically to cancer cells, and controlling its release in a controlled manner.
Used in Pharmaceutical Industry:
SB218078 is used in the pharmaceutical industry as a selective inhibitor of Chk1 for the development of novel therapeutic strategies against cancer. Its ability to enhance the cytotoxicity of DNA-damaging compounds makes it a promising candidate for combination therapies, potentially leading to more effective treatments with fewer side effects.
Biological Activity
Inhibitor of checkpoint kinase 1 (Chk1) that displays selectivity over other protein kinases (IC 50 values are 15, 250 and 1000 nM for Chk1, cdc2 and PKC respectively). Abrogates G 2 cell cycle arrest caused by γ -irradiation and topoisomerase I inhibition. Potentiates cytotoxicity of DNA-damaging drugs, enhancing the efficacy of some chemotherapeutics.
in vitro
SB-218078 (2.5-5 μM; 18 hours; HeLa cells) treatment abrogates G2 cell cycle arrest caused by either γ-irradiation or a topoisomerase I Topotecan inhibition.SB-218078 (500-625 μM; 96 hours; HeLa and HT-29 cells) treatment significantly increases the cytotoxicity of DNA damage .
in vivo
SB-218078 (5 mg/kg; intraperitoneal injection; for 16 hours; C57/Bl6 mice) treatment could promote a strong increase of γ-H2AX and apoptosis throughout the lymphoma, while having no effect on a healthy spleen in Myc-induced lymphomas mouse model.
target
chk1, cdc2 and pkc
IC 50
15, 250 and 1000 nm for chk1, cdc2 and pkc respectively
references
[1] jackson j r, gilmartin a g, imburgia c s, et al. an indolocarbazole inhibitor of human checkpoint kinase (chk1) abrogates cell cycle arrest caused by dna damage[j]. cancer research, 2000, 60(3): 566-572.[2] gasser s, orsulic s, brown e j, et al. the dna damage pathway regulates innate immune system ligands of the nkg2d receptor[j]. nature, 2005, 436(7054): 1186-1190.[3] alderton g k, galbiati l, griffith e, et al. regulation of mitotic entry by microcephalin and its overlap with atr signalling[j]. nature cell biology, 2006, 8(7): 725-733.[4] murga m, campaner s, lopez-contreras a j, et al. exploiting oncogene-induced replicative stress for the selective killing of myc-driven tumors[j]. nature structural & molecular biology, 2011, 18(12): 1331-1335.
Check Digit Verification of cas no
The CAS Registry Mumber 135897-06-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,5,8,9 and 7 respectively; the second part has 2 digits, 0 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 135897-06:
(8*1)+(7*3)+(6*5)+(5*8)+(4*9)+(3*7)+(2*0)+(1*6)=162
162 % 10 = 2
So 135897-06-2 is a valid CAS Registry Number.
InChI:InChI=1/C24H15N3O3/c28-23-19-17-11-5-1-3-7-13(11)26-15-9-10-16(30-15)27-14-8-4-2-6-12(14)18(22(27)21(17)26)20(19)24(29)25-23/h1-8,15-16H,9-10H2,(H,25,28,29)
