WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H201210
CAS#: 488832-69-5
Description: Elesclomol, also known as STA-4783, is a HSP-90 Inhibitor, and is a small-molecule bis(thio-hydrazide amide) with oxidative stress induction, pro-apoptotic, and potential antineoplastic activities. Elesclomol induces oxidative stress, creating high levels of reactive oxygen species (ROS), such as hydrogen peroxide, in both cancer cells and normal cells. Because tumor cells have elevated levels of ROS compared to normal cells, the increase in oxidative stress beyond baseline levels elevates ROS beyond sustainable levels, exhausting tumor cell antioxidant capacity, which may result in the induction of the mitochondrial apoptosis pathway.
Hodoodo Cat#: H201210
Name: Elesclomol
CAS#: 488832-69-5
Chemical Formula: C19H20N4O2S2
Exact Mass: 400.10
Molecular Weight: 400.520
Elemental Analysis: C, 56.98; H, 5.03; N, 13.99; O, 7.99; S, 16.01
Synonym: STA4783; STA-4783; STA 4783, Elesclomol.
IUPAC/Chemical Name: N'1,N'3-dimethyl-N'1,N'3-di(phenylcarbonothioyl)malonohydrazide
InChi Key: BKJIXTWSNXCKJH-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(NN(C)C(C1=CC=CC=C1)=S)CC(NN(C)C(C2=CC=CC=C2)=S)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Elesclomol (STA-4783) is a novel potent oxidative stress inducer that elicits pro-apoptosis events among tumor cells. |
| In vitro activity: | Treatment of cancer cells in vitro with elesclomol resulted in the rapid generation of reactive oxygen species (ROS) and the induction of a transcriptional gene profile characteristic of an oxidative stress response. Inhibition of oxidative stress by the antioxidant N-acetylcysteine blocked the induction of gene transcription by elesclomol. In addition, N-acetylcysteine blocked drug-induced apoptosis, indicating that ROS generation is the primary mechanism responsible for the proapoptotic activity of elesclomol. Excessive ROS production and elevated levels of oxidative stress are critical biochemical alterations that contribute to cancer cell growth. Thus, the induction of oxidative stress by elesclomol exploits this unique characteristic of cancer cells by increasing ROS levels beyond a threshold that triggers cell death. Reference: Mol Cancer Ther. 2008 Aug;7(8):2319-27. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18723479 |
| In vivo activity: | To investigate the impact of elesclomol on HS formation, the rabbit ear HS model was established. We created 6 full-thickness circular wounds on the ventral surface of each ear (Fig. 4A). The wounds were observed on days 5 to 7, and scar hyperplasia peaked after approximately 21 days. As shown in Fig. 4C, the wound areas on the rabbit ears in the no-treatment and vehicle groups consisted of prominent skin tissue with a tough texture, light red bulges, and hard areas. In contrast, the wound areas in the elesclomol group (0.2 mg elesclomol per wound area) appeared flatter and softer with a near-normal color. HE-stained sections of rabbit ear tissue collected 35 days after wounding showed numerous fibroblasts in the blank control and vehicle groups, along with abundant fibroblast proliferation and coarsely arranged collagen fibers (Fig. 4D). In contrast, the tissues from the elesclomol group were flatter and had a significantly smaller cross-sectional wound area. These findings were consistent with the overall wound appearance (Fig. 4C). In addition, Masson's trichrome staining was performed, which stained the collagen fibers blue, and the cells interspersed between the collagen fibers light gray. Masson stained images showed that, in the elesclomol group, the collagen fibers were arranged regularly and loosely, while in the blank-control and vehicle groups, the fibers were disordered, dense, and even formed spiral-like tangles (Fig. 4E). Analysis of the Masson-stained images showed that elesclomol treatment reduced the SEI (Fig. 4F), which is considered to be the most objective criterion for assessing scar formation. Reference: EBioMedicine. 2020 Apr;54:102715. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32251998/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 20.0 | 49.90 |
The following data is based on the product molecular weight 400.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | 1. Feng Y, Wu JJ, Sun ZL, Liu SY, Zou ML, Yuan ZD, Yu S, Lv GZ, Yuan FL. Targeted apoptosis of myofibroblasts by elesclomol inhibits hypertrophic scar formation. EBioMedicine. 2020 Apr;54:102715. doi: 10.1016/j.ebiom.2020.102715. Epub 2020 Apr 3. PMID: 32251998; PMCID: PMC7132150. 2. Guthrie LM, Soma S, Yuan S, Silva A, Zulkifli M, Snavely TC, Greene HF, Nunez E, Lynch B, De Ville C, Shanbhag V, Lopez FR, Acharya A, Petris MJ, Kim BE, Gohil VM, Sacchettini JC. Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice. Science. 2020 May 8;368(6491):620-625. doi: 10.1126/science.aaz8899. PMID: 32381719; PMCID: PMC7304446. |
| In vivo protocol: | 1. Feng Y, Wu JJ, Sun ZL, Liu SY, Zou ML, Yuan ZD, Yu S, Lv GZ, Yuan FL. Targeted apoptosis of myofibroblasts by elesclomol inhibits hypertrophic scar formation. EBioMedicine. 2020 Apr;54:102715. doi: 10.1016/j.ebiom.2020.102715. Epub 2020 Apr 3. PMID: 32251998; PMCID: PMC7132150. 2. Guthrie LM, Soma S, Yuan S, Silva A, Zulkifli M, Snavely TC, Greene HF, Nunez E, Lynch B, De Ville C, Shanbhag V, Lopez FR, Acharya A, Petris MJ, Kim BE, Gohil VM, Sacchettini JC. Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice. Science. 2020 May 8;368(6491):620-625. doi: 10.1126/science.aaz8899. PMID: 32381719; PMCID: PMC7304446. |
1: Blackman RK, Cheung-Ong K, Gebbia M, Proia DA, He S, Kepros J, Jonneaux A, Marchetti P, Kluza J, Rao PE, Wada Y, Giaever G, Nislow C. Mitochondrial electron transport is the cellular target of the oncology drug elesclomol. PLoS One. 2012;7(1):e29798. Epub 2012 Jan 11. PubMed PMID: 22253786; PubMed Central PMCID: PMC3256171.
2: Wu L, Zhou L, Liu DQ, Vogt FG, Kord AS. LC-MS/MS and density functional theory study of copper(II) and nickel(II) chelating complexes of elesclomol (a novel anticancer agent). J Pharm Biomed Anal. 2011 Jan 25;54(2):331-6. Epub 2010 Sep 15. PubMed PMID: 20933353.
3: O'Day S, Gonzalez R, Lawson D, Weber R, Hutchins L, Anderson C, Haddad J, Kong S, Williams A, Jacobson E. Phase II, randomized, controlled, double-blinded trial of weekly elesclomol plus paclitaxel versus paclitaxel alone for stage IV metastatic melanoma. J Clin Oncol. 2009 Nov 10;27(32):5452-8. Epub 2009 Oct 13. PubMed PMID: 19826135.
4: Qu Y, Wang J, Sim MS, Liu B, Giuliano A, Barsoum J, Cui X. Elesclomol, counteracted by Akt survival signaling, enhances the apoptotic effect of chemotherapy drugs in breast cancer cells. Breast Cancer Res Treat. 2010 Jun;121(2):311-21. Epub 2009 Jul 16. PubMed PMID: 19609669.
5: Wangpaichitr M, Wu C, You M, Maher JC, Dinh V, Feun LG, Savaraj N. N',N'-Dimethyl-N',N'-bis(phenylcarbonothioyl) Propanedihydrazide (Elesclomol) Selectively Kills Cisplatin Resistant Lung Cancer Cells through Reactive Oxygen Species (ROS). Cancers (Basel). 2009;1(1):23-38. PubMed PMID: 20535236; PubMed Central PMCID: PMC2882109.
6: Kirshner JR, He S, Balasubramanyam V, Kepros J, Yang CY, Zhang M, Du Z, Barsoum J, Bertin J. Elesclomol induces cancer cell apoptosis through oxidative stress. Mol Cancer Ther. 2008 Aug;7(8):2319-27. PubMed PMID: 18723479.
7: Molecule of the month. Elesclomol and obatoclax mesylate. Drug News Perspect. 2008 Mar;21(2):123-4. PubMed PMID: 18389103.
