Bosutinib (SKI-606)

• CAT Number: A000261
• CAS Number: 380843-75-4
• Molecular Formula: C₂₆H₂₉Cl₂N₅O₃
• Molecular Weight: 530.45
• Purity: ≥95%
• Target: Autophagy
• Solubility: >26.5mg/mL in DMSO
• Storage: 3 years -20C powder
• IUPAC Name: 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
• InChI: InChI=1S/C26H29Cl2N5O3/c1-32-6-8-33(9-7-32)5-4-10-36-25-13-21-18(11-24(25)35-3)26(17(15-29)16-30-21)31-22-14-23(34-2)20(28)12-19(22)27/h11-14,16H,4-10H2,1-3H3,(H,30,31)
• InChIKey: UBPYILGKFZZVDX-UHFFFAOYSA-N
• SMILES: CN1CCN(CC1)CCCOC2=C(C=C3C(=C2)N=CC(=C3NC4=CC(=C(C=C4Cl)Cl)OC)C#N)OC

Bosutinib (SKI-606)（Cat No.:A000261）is a potent tyrosine kinase inhibitor that primarily targets BCR-ABL and Src family kinases, making it an effective treatment for chronic myeloid leukemia (CML) with resistance or intolerance to prior therapies. By inhibiting these kinases, bosutinib disrupts cancer cell signaling pathways involved in proliferation and survival, particularly in CML cells with the Philadelphia chromosome mutation. Bosutinib also has activity against Src kinases, offering potential in targeting solid tumors. Its ability to overcome resistance makes it a valuable option in managing CML and other malignancies.

Reference

1. Redaelli S, Perini P, Ceccon M, Piazza R, Rigolio R, Mauri M, Boschelli F, Giannoudis A, Gambacorti-Passerini C. In vitro and in vivo identification of ABCB1 as an efflux transporter of bosutinib. J Hematol Oncol. 2015 Jul 7;8(1):81. PubMed PMID: 26149173.
2. Wang B, Cvetkovic D, Wang C, Chen L, Ma C. SU-E-T-668: Radiosensitizing Effect of Bosutinib On Prostate and Colon Cancers: A Pilot in Vitro Study. Med Phys. 2015 Jun;42(6):3490. doi: 10.1118/1.4925031. PubMed PMID: 26128331.
3. Takahashi N. [New treatment option for patient with CML-bosutinib]. Gan To Kagaku Ryoho. 2015 May;42(5):563-7. Japanese. PubMed PMID: 26054091.
4. Gambacorti-Passerini C, Kantarjian HM, Kim DW, Khoury HJ, Turkina AG, Brümmendorf TH, Matczak E, Bardy-Bouxin N, Shapiro M, Turnbull K, Leip E, Cortes JE. Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors. Am J Hematol. 2015 Jun 1. doi: 10.1002/ajh.24034. [Epub ahead of print] PubMed PMID: 26040495.
5. Abbas R, Boni J, Sonnichsen D. Effect of rifampin on the pharmacokinetics of bosutinib, a dual Src/Abl tyrosine kinase inhibitor, when administered concomitantly to healthy subjects. Drug Metabol Personal Ther. 2015 Mar;30(1):57-63. doi: 10.1515/dmdi-2014-0026. PubMed PMID: 25803093.
6. Doan V, Wang A, Prescott H. Bosutinib for the treatment of chronic myeloid leukemia. Am J Health Syst Pharm. 2015 Mar 15;72(6):439-47. doi: 10.2146/ajhp140221. Review. PubMed PMID: 25736937.
7. García-Gutiérrez V, Martinez-Trillos A, Lopez Lorenzo JL, Bautista G, Martin Mateos ML, Alvarez-Larrán A, Iglesias Pérez A, Romo Collado A, Fernandez A, Portero A, Cuevas B, Ruiz C, Romero E, Ortega F, Mata I, Tallón J, García Garay Mdel C, Ramirez Sánchez MJ, de Las Heras N, Giraldo P, Bobillo S, Guinea JM, Deben G, Valencia S, Sebrango A, Boqué C, Maestro B, Steegmann JL. Bosutinib shows low cross intolerance, in chronic myeloid leukemia patients treated in fourth line. Results of the Spanish compassionate use program. Am J Hematol. 2015 May;90(5):429-33. doi: 10.1002/ajh.23973. Epub 2015 Mar 30. PubMed PMID: 25683327.
8. Randall N, Courville EL, Baughn L, Afrin L, Ustun C. Bosutinib, a Lyn/Btk inhibiting tyrosine kinase inhibitor, is ineffective in advanced systemic mastocytosis. Am J Hematol. 2015 Apr;90(4):E74. doi: 10.1002/ajh.23942. Epub 2015 Mar 2. PubMed PMID: 25641616.
9. Nakaseko C, Takahashi N, Ishizawa K, Kobayashi Y, Ohashi K, Nakagawa Y, Yamamoto K, Miyamura K, Taniwaki M, Okada M, Kawaguchi T, Shibata A, Fujii Y, Ono C, Ohnishi K. A phase 1/2 study of bosutinib in Japanese adults with Philadelphia chromosome-positive chronic myeloid leukemia. Int J Hematol. 2015 Feb;101(2):154-64. doi: 10.1007/s12185-014-1722-8. Epub 2014 Dec 25. PubMed PMID: 25540064.
10. Nguyen T, Hawkins E, Kolluri A, Kmieciak M, Park H, Lin H, Grant S. Synergism between bosutinib (SKI-606) and the Chk1 inhibitor (PF-00477736) in highly imatinib-resistant BCR/ABL⁺ leukemia cells. Leuk Res. 2015 Jan;39(1):65-71. doi: 10.1016/j.leukres.2014.10.009. Epub 2014 Nov 11. PubMed PMID: 25465126; PubMed Central PMCID: PMC4413916.