For research use only. Not for therapeutic Use.
LY2603618（Cat No.:I005431）is a selective inhibitor of checkpoint kinase 1 (Chk1), a protein crucial for the DNA damage response and cell cycle regulation. By inhibiting Chk1, LY2603618 impairs the cell’s ability to repair DNA damage, particularly in cancer cells reliant on Chk1 for survival due to their high replication stress. This makes the compound an effective enhancer of DNA-damaging chemotherapies and radiation therapy, as it sensitizes cancer cells to these treatments. LY2603618 has been investigated in preclinical and clinical studies for potential use in treating various cancers, including lung and ovarian cancers.
| Catalog Number | I005431 |
| CAS Number | 911222-45-2 |
| Synonyms | IC-83;LY-2603618 |
| Molecular Formula | C18H22BrN5O3 |
| Purity | ≥95% |
| Target | Chk |
| Solubility | DMSO: ≤ 29.5 mg/mL |
| Storage | 3 years -20C powder |
| IC50 | 7 nM |
| IUPAC Name | 1-[5-bromo-4-methyl-2-[[(2S)-morpholin-2-yl]methoxy]phenyl]-3-(5-methylpyrazin-2-yl)urea |
| InChI | InChI=1S/C18H22BrN5O3/c1-11-5-16(27-10-13-8-20-3-4-26-13)15(6-14(11)19)23-18(25)24-17-9-21-12(2)7-22-17/h5-7,9,13,20H,3-4,8,10H2,1-2H3,(H2,22,23,24,25)/t13-/m0/s1 |
| InChIKey | SYYBDNPGDKKJDU-ZDUSSCGKSA-N |
| SMILES | CC1=CC(=C(C=C1Br)NC(=O)NC2=NC=C(N=C2)C)OC[C@@H]3CNCCO3 |
| Reference | </br>1:A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients. Laquente B, Lopez-Martin J, Richards D, Illerhaus G, Chang DZ, Kim G, Stella P, Richel D, Szcylik C, Cascinu S, Frassineti GL, Ciuleanu T, Hurt K, Hynes S, Lin J, Lin AB, Von Hoff D, Calvo E.BMC Cancer. 2017 Feb 15;17(1):137. doi: 10.1186/s12885-017-3131-x. PMID: 28202004 Free PMC Article</br>2:Phase I Study of CHK1 Inhibitor LY2603618 in Combination with Gemcitabine in Patients with Solid Tumors. Calvo E, Braiteh F, Von Hoff D, McWilliams R, Becerra C, Galsky MD, Jameson G, Lin J, McKane S, Wickremsinhe ER, Hynes SM, Bence Lin A, Hurt K, Richards D.Oncology. 2016;91(5):251-260. Epub 2016 Sep 7. PMID: 27598338 </br>3:Phase II evaluation of LY2603618, a first-generation CHK1 inhibitor, in combination with pemetrexed in patients with advanced or metastatic non-small cell lung cancer. Scagliotti G, Kang JH, Smith D, Rosenberg R, Park K, Kim SW, Su WC, Boyd TE, Richards DA, Novello S, Hynes SM, Myrand SP, Lin J, Smyth EN, Wijayawardana S, Lin AB, Pinder-Schenck M.Invest New Drugs. 2016 Oct;34(5):625-35. doi: 10.1007/s10637-016-0368-1. Epub 2016 Jun 27. PMID: 27350064 </br>4:LY2603618, a selective CHK1 inhibitor, enhances the anti-tumor effect of gemcitabine in xenograft tumor models. Barnard D, Diaz HB, Burke T, Donoho G, Beckmann R, Jones B, Barda D, King C, Marshall M.Invest New Drugs. 2016 Feb;34(1):49-60. doi: 10.1007/s10637-015-0310-y. Epub 2015 Nov 27. PMID: 26612134 </br>5:Phase I study of LY2603618, a CHK1 inhibitor, in combination with gemcitabine in Japanese patients with solid tumors. Doi T, Yoshino T, Shitara K, Matsubara N, Fuse N, Naito Y, Uenaka K, Nakamura T, Hynes SM, Lin AB.Anticancer Drugs. 2015 Nov;26(10):1043-53. doi: 10.1097/CAD.0000000000000278. PMID: 26288133 </br>6:Evaluation of the likelihood of a selective CHK1 inhibitor (LY2603618) to inhibit CYP2D6 with desipramine as a probe substrate in cancer patients. Hynes SM, Wickremsinhe E, Zhang W, Decker R, Ott J, Chandler J, Mitchell M.Biopharm Drug Dispos. 2015 Jan;36(1):49-63. doi: 10.1002/bdd.1922. Epub 2014 Nov 14. PMID: 25296725 </br>7:Preclinical analyses and phase I evaluation of LY2603618 administered in combination with pemetrexed and cisplatin in patients with advanced cancer. Calvo E, Chen VJ, Marshall M, Ohnmacht U, Hynes SM, Kumm E, Diaz HB, Barnard D, Merzoug FF, Huber L, Kays L, Iversen P, Calles A, Voss B, Lin AB, Dickgreber N, Wehler T, Sebastian M.Invest New Drugs. 2014 Oct;32(5):955-68. doi: 10.1007/s10637-014-0114-5. Epub 2014 Jun 20. PMID: 24942404 </br>8:The checkpoint 1 kinase inhibitor LY2603618 induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Wang FZ, Fei HR, Cui YJ, Sun YK, Li ZM, Wang XY, Yang XY, Zhang JG, Sun BL.Apoptosis. 2014 Sep;19(9):1389-98. doi: 10.1007/s10495-014-1010-3. PMID: 24928205 </br>9:Disposition and metabolism of LY2603618, a Chk-1 inhibitor following intravenous administration in patients with advanced and/or metastatic solid tumors. Wickremsinhe ER, Hynes SM, Palmieri MD, Mitchell MI, Abraham TL, Rehmel JF, Chana E, Jost LM, Cassidy KC.Xenobiotica. 2014 Sep;44(9):827-41. doi: 10.3109/00498254.2014.900589. Epub 2014 Mar 26. PMID: 24666335 </br>10:Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. King C, Diaz H, Barnard D, Barda D, Clawson D, Blosser W, Cox K, Guo S, Marshall M.Invest New Drugs. 2014 Apr;32(2):213-26. doi: 10.1007/s10637-013-0036-7. Epub 2013 Oct 10. PMID: 24114124 |
