For research use only. Not for therapeutic Use.
SCH900776（Cat No.:I005338）is a potent and selective inhibitor of checkpoint kinase 1 (CHK1), an enzyme crucial for the DNA damage response and cell cycle regulation. By inhibiting CHK1, SCH900776 sensitizes cancer cells to DNA-damaging agents, such as chemotherapy and radiation, by impairing their ability to repair damaged DNA and manage replication stress. This leads to increased apoptosis and enhanced anticancer activity. SCH900776 is primarily used in oncology research to investigate its potential in combination therapies, particularly for cancers that rely heavily on CHK1 for survival under genotoxic stress conditions.
| Catalog Number | I005338 |
| CAS Number | 891494-63-6 |
| Synonyms | (R)-6-bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine |
| Molecular Formula | C15H18BrN7 |
| Purity | ≥95% |
| Target | Checkpoint Kinase (Chk) |
| Solubility | DMSO > 50 mg/mL Ethanol 3 mg/mL |
| Storage | 3 years -20C powder |
| IC50 | 3 nM(Chk1) |
| IUPAC Name | 6-bromo-3-(1-methylpyrazol-4-yl)-5-[(3R)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidin-7-amine |
| InChI | InChI=1S/C15H18BrN7/c1-22-8-10(6-19-22)11-7-20-23-14(17)12(16)13(21-15(11)23)9-3-2-4-18-5-9/h6-9,18H,2-5,17H2,1H3/t9-/m1/s1 |
| InChIKey | GMIZZEXBPRLVIV-SECBINFHSA-N |
| SMILES | CN1C=C(C=N1)C2=C3N=C(C(=C(N3N=C2)N)Br)[C@@H]4CCCNC4 |
| Reference | 1:Mol Cancer Ther. 2012 Feb;11(2):427-38. doi: 10.1158/1535-7163.MCT-11-0406. Epub 2011 Dec 27. Preclinical development of the novel Chk1 inhibitor SCH900776 in combination with DNA-damaging agents and antimetabolites.Montano R,Chung I,Garner KM,Parry D,Eastman A, PMID: 22203733 PMCID: PMC3277678 DOI: 10.1158/1535-7163.MCT-11-0406 </br><span>Abstract:</span> Many anticancer agents damage DNA and arrest cell-cycle progression primarily in S or G(2) phase of the cell cycle. Previous studies with the topoisomerase I inhibitor SN38 have shown the efficacy of the Chk1 inhibitor UCN-01 to overcome this arrest and induce mitotic catastrophe. UCN-01 was limited in clinical trials by unfavorable pharmacokinetics. SCH900776 is a novel and more selective Chk1 inhibitor that potently inhibits Chk1 and abrogates cell-cycle arrest induced by SN38. Like UCN-01, abrogation of SN38-induced arrest enhances the rate of cell death but does not increase overall cell death. In contrast, SCH900776 reduced the growth-inhibitory concentration of hydroxyurea by 20- to 70-fold. A similar magnitude of sensitization was observed with cytarabine. A 5- to 10-fold sensitization occurred with gemcitabine, but no sensitization occurred with cisplatin, 5-fluorouracil, or 6-thioguanine. Sensitization occurred at hydroxyurea concentrations that marginally slowed DNA replication without apparent activation of Chk1, but this led to dependence on Chk1 that increased with time. For example, when added 18 hours after hydroxyurea, SCH900776 induced DNA double-strand breaks consistent with rapid collapse of replication forks. In addition, some cell lines were highly sensitive to SCH900776 alone, and these cells required lower concentrations of SCH900776 to sensitize them to hydroxyurea. We conclude that some tumors may be very sensitive to the combination of SCH900776 and hydroxyurea. Delayed administration of SCH900776 may be more effective than concurrent treatment. SCH900776 is currently in phase I clinical trials, and these results provide the rationale and schedule for future clinical trials. |
