| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
SB-218078 targets checkpoint kinase 1 (Chk1), a serine/threonine protein kinase that plays a critical role in the DNA damage response and cell cycle checkpoint control. By inhibiting Chk1 with an IC50 of 15 nM, SB-218078 prevents the phosphorylation of cdc25C, a key regulator of the G2/M checkpoint. This inhibition abrogates the DNA damage-induced cell cycle arrest, leading to premature mitotic entry and apoptosis in cells with DNA damage. The compound also weakly inhibits Cdc2 (IC50 = 250 nM) and PKC (IC50 = 1000 nM), and is a potent inhibitor of type I 5-phosphatase.
|
|---|---|
| ln Vitro |
Treatment with SB-218078 (2.5-5 μM; 18 hours; HeLa cells) reverses G2 cell cycle arrest brought on by topoisomerase I Topotecan inhibition or γ-irradiation[1]. Treatment with SB-218078 (500–625 μM; 96 hours) greatly improves the cytotoxicity of DNA damage in HeLa cells and HT-29 cells [1].
In vitro, SB-218078 acts as a potent and selective inhibitor of Chk1, inhibiting Chk1 phosphorylation of cdc25C with an IC50 of 15 nM. It shows weak inhibition of Cdc2 (IC50 = 250 nM) and PKC (IC50 = 1000 nM). The compound induces apoptosis through DNA damage and cell cycle arrest. SB-218078 is cell-permeable and has been used in various cellular models to study the role of Chk1 in the DNA damage response. Its selectivity for Chk1 over other kinases makes it a valuable tool for studying checkpoint signaling. |
| ln Vivo |
In a mouse model of Myc-induced lymphomas, SB-218078 (5 mg/kg; intraperitoneal injection; for 16 hours; C57/Bl6 mice) therapy may strongly enhance γ-H2AX and apoptosis within the lymphoma, but have no effect on a healthy spleen[2].
In vivo, SB-218078 has been studied as a potential therapeutic agent for cancer, particularly in combination with DNA-damaging agents. By inhibiting Chk1, the compound abrogates the G2/M checkpoint, sensitizing cancer cells to DNA-damaging chemotherapy and radiotherapy. However, specific in vivo efficacy data in animal models are not extensively detailed in the available literature. The compound is primarily a research tool for studying the DNA damage response. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for SB-218078 are kinase activity assays using purified recombinant Chk1, Cdc2, or PKC proteins. The enzyme is incubated with a peptide substrate and ATP in the presence of varying concentrations of SB-218078, and the extent of substrate phosphorylation is measured. The IC50 for inhibition of Chk1 kinase activity is determined from dose-response curves. Selectivity is assessed by testing the compound against a panel of other kinases. These assays confirm the compound's selective inhibition of Chk1.
|
| Cell Assay |
Cell Cycle Analysis[1]
Cell Types: HeLa cells Tested Concentrations: 2.5 μM, 5 μM Incubation Duration: 18 hrs (hours) Experimental Results: Abrogated G2 cell cycle arrest caused by γ-irradiation and topoisomerase I inhibition. Cell Cytotoxicity Assay[1] Cell Types: HeLa and HT-29 cells Tested Concentrations: 500 nM, 625 nM Incubation Duration: 96 hrs (hours) Experimental Results: Enhanced cytotoxicity of DNA damage. In vitro cellular assays for SB-218078 are performed using cancer cell lines treated with DNA-damaging agents (e.g., cisplatin, doxorubicin, or ionizing radiation). Cells are treated with SB-218078, and Chk1 phosphorylation of cdc25C is assessed by Western blotting. Cell cycle distribution is analyzed by flow cytometry to assess abrogation of the G2/M checkpoint. Apoptosis is evaluated using annexin V staining or caspase activity assays. DNA damage markers such as γ-H2AX are measured to confirm the induction of DNA damage. These assays confirm the compound's ability to inhibit Chk1 signaling in cells. |
| Animal Protocol |
Animal/Disease Models: C57/BL6 black mouse injected with ARF-/- lymphomas[2]
Doses: 5 mg/kg Route of Administration: intraperitoneal (ip)injection; for 16 hrs (hours) Experimental Results: Promoted a strong increase of γ-H2AX and apoptosis throughout the lymphoma. In vivo animal experiments for SB-218078 are conducted in xenograft mouse models of human cancers. Immunocompromised mice are implanted with human tumor cells and treated with SB-218078 in combination with DNA-damaging agents (e.g., cisplatin or radiation) via oral or intraperitoneal administration. Tumor growth inhibition is monitored, and endpoints include tumor volume, tumor weight, and survival. Pharmacodynamic markers such as Chk1 phosphorylation and apoptosis in tumor tissues are assessed. |
| ADME/Pharmacokinetics |
SB-218078 has a molecular weight of 393.40 g/mol and a molecular formula of C24H15N3O3. The compound is an indolocarbazole derivative. It is soluble in DMSO and other organic solvents. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability have not been extensively reported. As a research compound, SB-218078 is primarily used in in vitro studies, and its in vivo pharmacokinetics would require further investigation.
|
| Toxicity/Toxicokinetics |
SB-218078 has been evaluated in preclinical studies and has been reported to be well-tolerated at effective doses. No significant toxicity has been reported in the available literature. However, comprehensive toxicology studies would be necessary to fully assess the compound's safety profile for clinical development. As a Chk1 inhibitor, SB-218078 may have potential toxicity to normal cells, particularly in combination with DNA-damaging agents.
|
| References |
|
| Additional Infomation |
LSM-1274 is an indolecarbazole compound. SB-218078 is a specific inhibitor of CHK1.
SB-218078 is a potent, selective, ATP-competitive, and cell-permeable inhibitor of checkpoint kinase 1 (Chk1). It inhibits Chk1 phosphorylation of cdc25C with an IC50 of 15 nM and weakly inhibits Cdc2 (IC50 = 250 nM) and PKC (IC50 = 1000 nM). The compound induces apoptosis through DNA damage and cell cycle arrest. SB-218078 is also a potent inhibitor of type I 5-phosphatase. It is a research compound used to study the DNA damage response and is not an approved drug. |
| Molecular Formula |
C24H15N3O3
|
|---|---|
| Molecular Weight |
393.39
|
| Exact Mass |
393.111
|
| CAS # |
135897-06-2
|
| PubChem CID |
3387354
|
| Appearance |
Light yellow to yellow solid powder
|
| Index of Refraction |
1.97
|
| LogP |
4.363
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
0
|
| Heavy Atom Count |
30
|
| Complexity |
754
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
OTPNDVKVEAIXTI-IYBDPMFKSA-N
|
| InChi Code |
InChI=1S/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)/t15-,16+
|
| Chemical Name |
(5R,8S)-7,8-dihydro-5H-16-oxa-4b,8a,14-triaza-5,8-methanodibenzo[b,h]cycloocta[jkl]cyclopenta[e]-as-indacene-13,15(6H,14H)-dione
|
| Synonyms |
SB 218078 SB218078 SB-218078.
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5420 mL | 12.7100 mL | 25.4201 mL | |
| 5 mM | 0.5084 mL | 2.5420 mL | 5.0840 mL | |
| 10 mM | 0.2542 mL | 1.2710 mL | 2.5420 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
