Back to products

Browse products

Approved anticancer agents

Anticancer agents in trials

Anticancer agents in preclinical trials

Anticancer molecular libraries

MedKoo product information:

KRX-0601

Description of KRX-0601: KRX-0601, also known as UCN-01, is a synthetic derivative of staurosporine with antineoplastic activity. 7-hydroxystaurosporine inhibits many phosphokinases, including the serine/threonine kinase AKT, calcium-dependent protein kinase C, and cyclin-dependent kinases. This agent arrests tumor cells in the G1/S of the cell cycle and prevents nucleotide excision repair by inhibiting the G2 checkpoint kinase chk1, resulting in apoptosis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus) .

Current developer:    Kyowa Pharmaceutical, Inc. .

KRX-0601 is a novel multi-kinase inhibitor for the treatment of cancer which, in pre-clinical models, has demonstrated a synergistic effect with agents inhibiting the PI3K pathway, including KRX-0401. KRX-0601 is currently in several Phase II clinical trials both as a single agent and in combination with other anticancer agents which are being conducted under the direction and sponsorship of the National Cancer Institute. KRX-0601 is an anticancer drug that belongs to the family of drugs called staurosporine analogs which have demonstrated an ability to inhibit multiple kinases involved in cell-cycle progression and apoptosis, including Chk-1 and PDK1. In pre-clinical studies, KRX-0601 has demonstrated synergistic effect with DNA-damaging agents including chemotherapy and radiation therapy. In-vitro, KRX-0601 has been shown to be synergistic with agents affecting the PI3-K pathway including KRX-0401 and mTOR inhibitors. In clinical trials, as reported by investigators at the National Cancer Institute, durable single-agent responses have been seen in patients with anaplastic large-cell lymphoma. We expect to continue exploring the potential utility of KRX-0601 over the next year.

 1: Ullal AJ, Pisetsky DS. The release of microparticles by Jurkat leukemia T cells treated with staurosporine and related kinase inhibitors to induce apoptosis. Apoptosis. 2010 May;15(5):586-96. PubMed PMID: 20146001.

2: Jiang Z, Jin S, Yalowich JC, Brown KD, Rajasekaran B. The mismatch repair system modulates curcumin sensitivity through induction of DNA strand breaks and activation of G2-M checkpoint. Mol Cancer Ther. 2010 Mar;9(3):558-68. Epub 2010 Feb 9. PubMed PMID: 20145018; PubMed Central PMCID: PMC2837109.

3: Despras E, Daboussi F, Hyrien O, Marheineke K, Kannouche PL. ATR/Chk1 pathway is essential for resumption of DNA synthesis and cell survival in UV-irradiated XP variant cells. Hum Mol Genet. 2010 May 1;19(9):1690-701. Epub 2010 Feb 1. PubMed PMID: 20123862.

4: Thompson AF, Levin LA. Neuronal differentiation by analogs of staurosporine. Neurochem Int. 2010 Mar;56(4):554-60. Epub 2010 Jan 4. PubMed PMID: 20043966; PubMed Central PMCID: PMC2831141.

5: Varmark H, Kwak S, Theurkauf WE. A role for Chk2 in DNA damage induced mitotic delays in human colorectal cancer cells. Cell Cycle. 2010 Jan 15;9(2):312-20. Epub 2010 Jan 23. PubMed PMID: 20023427.

6: Bork U, Lee WK, Kuchler A, Dittmar T, Thévenod F. Cadmium-induced DNA damage triggers G(2)/M arrest via chk1/2 and cdc2 in p53-deficient kidney proximal tubule cells. Am J Physiol Renal Physiol. 2010 Feb;298(2):F255-65. Epub 2009 Nov 18. PubMed PMID: 19923412.

7: Kummar S, Gutierrez ME, Gardner ER, Figg WD, Melillo G, Dancey J, Sausville EA, Conley BA, Murgo AJ, Doroshow JH. A phase I trial of UCN-01 and prednisone in patients with refractory solid tumors and lymphomas. Cancer Chemother Pharmacol. 2010 Jan;65(2):383-9. Epub 2009 Nov 6. PubMed PMID: 19894051; PubMed Central PMCID: PMC2854012.

8: Khan N, Mupparaju SP, Hou H, Lariviere JP, Demidenko E, Swartz HM, Eastman A. Radiotherapy in conjunction with 7-hydroxystaurosporine: a multimodal approach with tumor pO2 as a potential marker of therapeutic response. Radiat Res. 2009 Nov;172(5):592-7. PubMed PMID: 19883227; PubMed Central PMCID: PMC2785035.

9: Cavelier C, Didier C, Prade N, Mansat-De Mas V, Manenti S, Recher C, Demur C, Ducommun B. Constitutive activation of the DNA damage signaling pathway in acute myeloid leukemia with complex karyotype: potential importance for checkpoint targeting therapy. Cancer Res. 2009 Nov 15;69(22):8652-61. Epub 2009 Oct 20. PubMed PMID: 19843865.

10: Kondoh E, Mori S, Yamaguchi K, Baba T, Matsumura N, Cory Barnett J, Whitaker RS, Konishi I, Fujii S, Berchuck A, Murphy SK. Targeting slow-proliferating ovarian cancer cells. Int J Cancer. 2010 May 15;126(10):2448-56. PubMed PMID: 19795452.

11: Chen S, Maya-Mendoza A, Zeng K, Tang CW, Sims PF, Loric J, Jackson DA. Interaction with checkpoint kinase 1 modulates the recruitment of nucleophosmin to chromatin. J Proteome Res. 2009 Oct;8(10):4693-704. PubMed PMID: 19694479.

12: Kuntz K, O'Connell MJ. The G(2) DNA damage checkpoint: could this ancient regulator be the Achilles heel of cancer? Cancer Biol Ther. 2009 Aug;8(15):1433-9. Epub 2009 Aug 22. Review. PubMed PMID: 19574738.

13: Lapenna S, Giordano A. Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. Review. PubMed PMID: 19568282.

14: Barakat KH, Torin Huzil J, Luchko T, Jordheim L, Dumontet C, Tuszynski J. Characterization of an inhibitory dynamic pharmacophore for the ERCC1-XPA interaction using a combined molecular dynamics and virtual screening approach. J Mol Graph Model. 2009 Sep;28(2):113-30. Epub 2009 May 4. PubMed PMID: 19473860.

15: Kumari D, Somma V, Nakamura AJ, Bonner WM, D'Ambrosio E, Usdin K. The role of DNA damage response pathways in chromosome fragility in Fragile X syndrome. Nucleic Acids Res. 2009 Jul;37(13):4385-92. Epub 2009 May 21. PubMed PMID: 19465392; PubMed Central PMCID: PMC2715245.

16: Chen CC, Kennedy RD, Sidi S, Look AT, D'Andrea A. CHK1 inhibition as a strategy for targeting Fanconi Anemia (FA) DNA repair pathway deficient tumors. Mol Cancer. 2009 Apr 16;8:24. PubMed PMID: 19371427; PubMed Central PMCID: PMC2672921.

17: Wang X, Lui VC, Poon RT, Lu P, Poon RY. DNA damage mediated s and g(2) checkpoints in human embryonal carcinoma cells. Stem Cells. 2009 Mar;27(3):568-76. PubMed PMID: 19259937; PubMed Central PMCID: PMC2798066.