Elesclomol

• CAT Number: I000036
• CAS Number: 488832-69-5
• Molecular Formula: C19H20N4O2S2
• Molecular Weight: 400.5
• Purity: ≥95%
• Synonyms: 1-N/’,3-N/’-bis(benzenecarbonothioyl)-1-N/’,3-N/’-dimethylpropanedihydrazide
• Target: HSP
• Solubility: DMSO: ≥ 30 mg/mL
• Storage: 3 years -20C powder
• InChI: InChI=1S/C19H20N4O2S2/c1-22(18(26)14-9-5-3-6-10-14)20-16(24)13-17(25)21-23(2)19(27)15-11-7-4-8-12-15/h3-12H,13H2,1-2H3,(H,20,24)(H,21,25)
• InChIKey: BKJIXTWSNXCKJH-UHFFFAOYSA-N
• SMILES: O=C(NN(C)C(C1=CC=CC=C1)=S)CC(NN(C)C(C2=CC=CC=C2)=S)=O

Elesclomol (CAT: I000036) is a small molecule investigational drug with potential anticancer properties. It acts by inducing oxidative stress and selectively targeting cancer cells. Elesclomol promotes the accumulation of reactive oxygen species (ROS) in cancer cells, leading to mitochondrial dysfunction and subsequent apoptosis. This compound has shown efficacy against various types of cancer, including melanoma and ovarian cancer, both as a single agent and in combination with other chemotherapy drugs. Elesclomol’s mechanism of action involves disrupting the balance between ROS production and antioxidant defense systems, ultimately leading to cancer cell death. Clinical trials are ongoing to further evaluate the safety and efficacy of Elesclomol in cancer treatment.

Overview of Clinical Research

Originator: Synta Pharmaceuticals
Class: Antineoplastics; Hydrazines; Ketones; Small molecules; Thiones
Mechanism of Action: Apoptosis stimulants; Chelating agents; HSP70 heat shock protein stimulants; Reactive oxygen species stimulants
Orphan Drug Status: Yes – Malignant melanoma

Reference

1:Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells. Kwan SY, Cheng X, Tsang YT, Choi JS, Kwan SY, Izaguirre DI, Kwan HS, Gershenson DM, Wong KK.Oncotarget. 2016 Aug 30;7(35):56933-56943. doi: 10.18632/oncotarget.10921. PMID: 27486766 Free PMC Article
2:A phase I study of elesclomol sodium in patients with acute myeloid leukemia. Hedley D, Shamas-Din A, Chow S, Sanfelice D, Schuh AC, Brandwein JM, Seftel MD, Gupta V, Yee KW, Schimmer AD.Leuk Lymphoma. 2016 Oct;57(10):2437-40. doi: 10.3109/10428194.2016.1138293. Epub 2016 Feb 5. No abstract available. PMID: 26732437
3:Cellular mechanisms of the cytotoxicity of the anticancer drug elesclomol and its complex with Cu(II). Hasinoff BB, Wu X, Yadav AA, Patel D, Zhang H, Wang DS, Chen ZS, Yalowich JC.Biochem Pharmacol. 2015 Feb 1;93(3):266-76. doi: 10.1016/j.bcp.2014.12.008. Epub 2014 Dec 27. PMID: 25550273
4:An /enhanced PET/-based fluorescent probe with ultrasensitivity for imaging basal and elesclomol-induced HClO in cancer cells. Zhu H, Fan J, Wang J, Mu H, Peng X.J Am Chem Soc. 2014 Sep 17;136(37):12820-3. doi: 10.1021/ja505988g. Epub 2014 Sep 3. PMID: 25171114
5:The cytotoxicity of the anticancer drug elesclomol is due to oxidative stress indirectly mediated through its complex with Cu(II). Hasinoff BB, Yadav AA, Patel D, Wu X.J Inorg Biochem. 2014 Aug;137:22-30. doi: 10.1016/j.jinorgbio.2014.04.004. Epub 2014 Apr 16. PMID: 24798374
6:Synthesis, crystallographic characterization and electrochemical property of a copper(II) complex of the anticancer agent elesclomol. Vo NH, Xia Z, Hanko J, Yun T, Bloom S, Shen J, Koya K, Sun L, Chen S.J Inorg Biochem. 2014 Jan;130:69-73. doi: 10.1016/j.jinorgbio.2013.10.005. Epub 2013 Oct 12. PMID: 24176921
7:Syntheses and antitumor activities of N/’1,N/’3-dialkyl-N/’1,N/’3-di-(alkylcarbonothioyl) malonohydrazide: the discovery of elesclomol. Chen S, Sun L, Koya K, Tatsuta N, Xia Z, Korbut T, Du Z, Wu J, Liang G, Jiang J, Ono M, Zhou D, Sonderfan A.Bioorg Med Chem Lett. 2013 Sep 15;23(18):5070-6. doi: 10.1016/j.bmcl.2013.07.032. Epub 2013 Jul 25. PMID: 23937981
8:Molecular mechanisms of the biological activity of the anticancer drug elesclomol and its complexes with Cu(II), Ni(II) and Pt(II). Yadav AA, Patel D, Wu X, Hasinoff BB.J Inorg Biochem. 2013 Sep;126:1-6. doi: 10.1016/j.jinorgbio.2013.04.013. Epub 2013 Apr 28. PMID: 23707906
9:Final results of phase III SYMMETRY study: randomized, double-blind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma. O/’Day SJ, Eggermont AM, Chiarion-Sileni V, Kefford R, Grob JJ, Mortier L, Robert C, Schachter J, Testori A, Mackiewicz J, Friedlander P, Garbe C, Ugurel S, Collichio F, Guo W, Lufkin J, Bahcall S, Vukovic V, Hauschild A.J Clin Oncol. 2013 Mar 20;31(9):1211-8. doi: 10.1200/JCO.2012.44.5585. Epub 2013 Feb 11. PMID: 23401447
10:The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Nagai M, Vo NH, Shin Ogawa L, Chimmanamada D, Inoue T, Chu J, Beaudette-Zlatanova BC, Lu R, Blackman RK, Barsoum J, Koya K, Wada Y.Free Radic Biol Med. 2012 May 15;52(10):2142-50. doi: 10.1016/j.freeradbiomed.2012.03.017. Epub 2012 Apr 17. PMID: 22542443