Treosulfan

• CAT Number: I003037
• CAS Number: 299-75-2
• Molecular Formula: C6H14O8S2
• Molecular Weight: 278.3
• Purity: ≥95%
• Solubility: 10 mM in DMSO
• Storage: Store at RT
• IUPAC Name: [(2S,3S)-2,3-dihydroxy-4-methylsulfonyloxybutyl] methanesulfonate
• InChI: InChI=1S/C6H14O8S2/c1-15(9,10)13-3-5(7)6(8)4-14-16(2,11)12/h5-8H,3-4H2,1-2H3/t5-,6-/m0/s1
• InChIKey: YCPOZVAOBBQLRI-WDSKDSINSA-N
• SMILES: CS(=O)(=O)OCC(C(COS(=O)(=O)C)O)O

Treosulfan (CAT: I003037) is an alkylating agent that is widely used in conventional chemotherapy regimens, as well as high-dose chemotherapy. When administered, treosulfan is converted into an active bifunctional sulfonate alkylating agent. It exerts its effects by forming covalent bonds with DNA, leading to DNA crosslinking and subsequent disruption of DNA replication and transcription processes. Treosulfan has myeloablative properties, meaning it can suppress bone marrow function, and it also exhibits immunosuppressive and antineoplastic activities. Its ability to achieve high plasma concentrations makes it an effective treatment option for certain malignancies.

Overview of Clinical Research

Treosulfan is an alkylating agent and a DNA cross linking agent as well as a DNA synthesis inhibitor. It has been granted for the orphan drug status in transplant rejection. 

Reference

1:Determination of prodrug treosulfan and its biologically active monoepoxide in rat plasma, liver, lungs, kidneys, muscle, and brain by HPLC-ESI-MS/MS method. Romański M, Kasprzyk A, Teżyk A, Widerowska A, Żaba C, Główka F.J Pharm Biomed Anal. 2017 Jun 5;140:122-129. doi: 10.1016/j.jpba.2017.03.023. Epub 2017 Mar 18. PMID: 28346882
2:Kinetic and Mechanistic Study of the pH-Dependent Activation (Epoxidation) of Prodrug Treosulfan Including the Reaction Inhibition in a Borate Buffer. Romański M, Ratajczak W, Główka F.J Pharm Sci. 2017 Mar 22. pii: S0022-3549(17)30175-2. doi: 10.1016/j.xphs.2017.03.018. [Epub ahead of print] PMID: 28342883
3:Long-term outcome after a treosulfan-based conditioning regimen for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Nagler A, Labopin M, Beelen D, Ciceri F, Volin L, Shimoni A, Foá R, Milpied N, Peccatori J, Polge E, Mailhol A, Mohty M, Savani BN.Cancer. 2017 Mar 22. doi: 10.1002/cncr.30646. [Epub ahead of print] PMID: 28329410
4:Treosulfan-Based Conditioning Regimen in Sibling and Alternative Donor Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease. Marzollo A, Calore E, Tumino M, Pillon M, Gazzola MV, Destro R, Colombatti R, Marson P, Tison T, Colpo A, Mainardi C, Gabelli M, Boaro MP, Rossin S, Strano A, Quaglia N, Menzato F, Basso G, Sainati L, Messina C.Mediterr J Hematol Infect Dis. 2017 Feb 15;9(1):e2017014. doi: 10.4084/MJHID.2017.014. eCollection 2017. PMID: 28293402 Free PMC Article
5:Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation. Sakellari I, Mallouri D, Gavriilaki E, Batsis I, Kaliou M, Constantinou V, Papalexandri A, Lalayanni C, Vadikolia C, Athanasiadou A, Yannaki E, Sotiropoulos D, Smias C, Anagnostopoulos A.Biol Blood Marrow Transplant. 2017 Mar;23(3):445-451. doi: 10.1016/j.bbmt.2016.11.023. Epub 2016 Nov 30. PMID: 27914967
6:Similar outcome after allogeneic stem cell transplantation with a modified FLAMSA conditioning protocol substituting 4 Gy TBI with treosulfan in an elderly population with high-risk AML. Holtick U, Herling M, Pflug N, Chakupurakal G, Leitzke S, Wolf D, Hallek M, Scheid C, Chemnitz JM.Ann Hematol. 2017 Mar;96(3):479-487. doi: 10.1007/s00277-016-2887-4. Epub 2016 Dec 1. PMID: 27909887
7:A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO). Sehouli J, Tomè O, Dimitrova D, Camara O, Runnebaum IB, Tessen HW, Rautenberg B, Chekerov R, Muallem MZ, Lux MP, Trarbach T, Gitsch G.J Cancer Res Clin Oncol. 2017 Mar;143(3):541-550. doi: 10.1007/s00432-016-2307-0. Epub 2016 Nov 28. PMID: 27896440 Free PMC Article
8:Morillo-Gutierrez B, Beier R, Rao K, et al. Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience. Blood. 2016;128(3):440-448. [No authors listed]Blood. 2016 Nov 24;128(21):2585. No abstract available. PMID: 27884839 Free PMC Article
9:Ocular disposition of treosulfan and its active epoxy-transformers following intravenous administration in rabbits. Romański M, Kasprzyk A, Karbownik A, Główka FK.Drug Metab Pharmacokinet. 2016 Oct;31(5):356-362. doi: 10.1016/j.dmpk.2016.07.001. Epub 2016 Jul 14. PMID: 27662779
10:Suppressive effects of low-dose 5-fluorouracil, busulfan or treosulfan on the expansion of circulatory neutrophils and myeloid derived immunosuppressor cells in tumor-bearing mice. Abedi-Valugerdi M, Wolfsberger J, Pillai PR, Zheng W, Sadeghi B, Zhao Y, Hassan M.Int Immunopharmacol. 2016 Nov;40:41-49. doi: 10.1016/j.intimp.2016.08.023. Epub 2016 Aug 28. PMID: 27580414