JTE-607 HCl

• CAS: 188791-09-5
• Catalog Number: ACM188791095
• Category: Inhibitors
• Molecular Weight: 597.36
• Molecular Formula: C25H33Cl4N3O5
• Description: JTE-607, also known as TO-207, is a cytokine production inhibitor potentially for the treatment of systemic inflammatory response, and induces apoptosis accompanied by an increase in p21waf1/cip1 in acute myelogenous leukemia cells.
• Synonyms: TO-207; TO 207; TO207; JTE-607; JTE 607; JTE 607; JTE-607 HCl; JTE-607 dihydrochloride
• IUPAC Name: N-[3,5-Dichloro-2-hydroxy-4-[2-(4-methyl-1-piperazinyl)ethoxy]benzoyl]-L-phenylalanine ethyl ester dihydrochloride
• Canonical SMILES: O=C(OCC)[C@H](CC1=CC=CC=C1)NC(C2=CC(Cl)=C(OCCN3CCN(C)CC3)C(Cl)=C2O)=O.[H]Cl.[H]Cl
• InChI: InChI=1S/C25H31Cl2N3O5.2ClH/c1-3-34-25(33)20(15-17-7-5-4-6-8-17)28-24(32)18-16-19(26)23(21(27)22(18)31)35-14-13-30-11-9-29(2)10-12-30;;/h4-8,16,20,31H,3,9-15H2,1-2H3,(H,28,32);2*1H/t20-;;/m0../s1
• InChI Key: JUJAUEQJEWIWCQ-FJSYBICCSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 188791-71-1 (free base); 188791-09-5 (HCl)
• Biological Target: JTE-607 is a highly selective inflammatory cytokine synthesis inhibitor that inhibits inflammatory cytokine production, including TNF-α, IL-1β, IL-6, IL-8 and IL-10, from LPS-stimulated human PBMCs, with IC50s of 11, 5.9, 8.8, 7.3 and 9.1 nM, respectively.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 50.27; H, 5.57; Cl, 23.74; N, 7.03; O, 13.39
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: The suppressive effect of JTE-607 was characterized on the growth of AML cells in terms of apoptosis and cell-cycle arrest at the molecular level. To evaluate whether JTE-607 induces apoptosis, U-937 cells cultured in the presence or absence of JTE-607 were stained with FITC-conjugated anti-Annexin V and PI. The result of flow cytometry analysis showed that Annexin V-positive/PI-negative apoptotic cells and PI-positive necrotic cells emerged after a 2-day exposure to JTE-607, and the proportion of those cells was increased concentration dependently. In the cell-cycle analysis, the proportion of the cells in the S-phase was increased when U-937 cells were exposed to over 0.1-0.3 μm of JTE-607 for 1 day. A significant decrease in c-Myc and an increase in p21waf1/cip1 occurred after 2-48 h exposure with JTE-607. Together, these results suggest that JTE-607 exerts its antiproliferative effect against AML cells through the sequential process including cell-cycle arrest at the S-phase and induction of apoptotic cell death.; Reference: Cancer Sci. 2010 Mar;101(3):774-81. https://pubmed.ncbi.nlm.nih.gov/20028380/
• In Vivo Activity: Mice bearing established leukemia were injected with JTE-607 at 100 mg/kg on day 18 and sacrificed 1h after the injection. Human cytokine mRNA levels in the bone marrow cells were then determined by quantitative RT-PCR and normalized to human GAPDH mRNA levels. The results show that single injection of JTE-607 dramatically and rapidly reduced human IL-6 and IL-8 mRNA; in contrast, human GAPDH mRNA levels were not altered. Moreover, it was observed that human VEGF mRNA levels were also reduced to a lesser extent than the two proinflammatory cytokines. In aggregate, these data indicate that JTE-607 is able to suppress both the growth and accompanying cytokine/growth factor production from AML cells significantly in an in vivo milieu.; Reference: Cancer Sci. 2010 Mar;101(3):774-81. https://pubmed.ncbi.nlm.nih.gov/20028380/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).