CI-994

• CAT Number: I000472
• CAS Number: 112522-64-2
• Molecular Formula: C₁₅H₁₅N₃O₂
• Molecular Weight: 269.3
• Purity: ≥95%
• Target: HDAC
• Solubility: DMSO: ≥ 58 mg/mL
• Storage: 3 years -20C powder
• IC50: 0.57 uM (For HDAC1,MTT assay)
• InChI: InChI=1S/C15H15N3O2/c1-10(19)17-12-8-6-11(7-9-12)15(20)18-14-5-3-2-4-13(14)16/h2-9H,16H2,1H3,(H,17,19)(H,18,20)
• InChIKey: VAZAPHZUAVEOMC-UHFFFAOYSA-N
• SMILES: CC(=O)NC1=CC=C(C=C1)C(=O)NC2=CC=CC=C2N

CI-994 (Tacedinaline) is an anti-cancer drug which inhibits HDAC1 with IC50 of 0.57 μM and causes G1 cell cycle arrest.IC50 Value: 0.57 uM (For HDAC1,MTT assay)Target: HDAC1in vitro: Different CI-994 concentrations were tested, ranging from 0.01 to 160 microM at 24, 48, and 72 h of treatment inA-549 (adenocarcinoma) and LX-1 (squamous cell carcinoma) ,with MTT assay. A concentration-dependent cell survival inhibition was observed, with an IC50 at 80 microM. The effect of CI-994, as demonstrated by recovery experiments, was cytostatic and seemed to be superimposable in both cell lines. Cytofluorimetric analysis to assess cell cycle perturbation and apoptosis was performed after 24 h of treatment, indicating a cell block with concomitant increase at G0/G1 phase, a reduction at S phase level at 20, 40, 80, and 160 microM, and apoptosis at the higher concentration (160 microM) [1].in vivo: CI-994 had the same spectrum of activity in vivo as dinaline. It also behaved similarly in schedule comparison/toxicity trials. Prolonged administration with lower drug doses was more effective than short-term therapy at higher individual doses. If doses were kept between 40 and 60 mg/kg/injection, prolonged administration (> 50 days) was tolerated with no gross toxicity. Doses > or = 90 mg/kg/injection caused lethality after 4-5 days of administration[2]. IC994 is currently in Phase I/II clinical trials, combining with gemcitabine[3].Clinical trail: CI-994 is in Phase III clinical trial in patients with Lung Cancer.

Reference

1:Class I HDAC imaging using [ (3)H]CI-994 autoradiography. Wang Y, Zhang YL, Hennig K, Gale JP, Hong Y, Cha A, Riley M, Wagner F, Haggarty SJ, Holson E, Hooker J.Epigenetics. 2013 Jul;8(7):756-64. doi: 10.4161/epi.25202. Epub 2013 Jun 11. PMID: 23803584 Free PMC Article2:Synthesis and biological evaluation of glucuronide prodrugs of the histone deacetylase inhibitor CI-994 for application in selective cancer chemotherapy. Thomas M, Clarhaut J, Tranoy-Opalinski I, Gesson JP, Roche J, Papot S.Bioorg Med Chem. 2008 Sep 1;16(17):8109-16. doi: 10.1016/j.bmc.2008.07.048. Epub 2008 Jul 23. PMID: 18692397 3:CI-994 (N-acetyl-dinaline) in combination with conventional anti-cancer agents is effective against acute myeloid leukemia in vitro and in vivo. Hubeek I, Comijn EM, Van der Wilt CL, Merriman RL, Padron JM, Kaspers GJ, Peters GJ.Oncol Rep. 2008 Jun;19(6):1517-23. PMID: 18497959 4:Improved synthesis of histone deacetylase inhibitors (HDIs) (MS-275 and CI-994) and inhibitory effects of HDIs alone or in combination with RAMBAs or retinoids on growth of human LNCaP prostate cancer cells and tumor xenografts. Gediya LK, Belosay A, Khandelwal A, Purushottamachar P, Njar VC.Bioorg Med Chem. 2008 Mar 15;16(6):3352-60. doi: 10.1016/j.bmc.2007.12.007. Epub 2007 Dec 8. PMID: 18166465 Free PMC Article5:Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study. Richards DA, Boehm KA, Waterhouse DM, Wagener DJ, Krishnamurthi SS, Rosemurgy A, Grove W, Macdonald K, Gulyas S, Clark M, Dasse KD.Ann Oncol. 2006 Jul;17(7):1096-102. Epub 2006 Apr 26. PMID: 16641168 6:In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines. Loprevite M, Tiseo M, Grossi F, Scolaro T, Semino C, Pandolfi A, Favoni R, Ardizzoni A.Oncol Res. 2005;15(1):39-48. PMID: 15839304 7:Phase I study of oral CI-994 in combination with carboplatin and paclitaxel in the treatment of patients with advanced solid tumors. Pauer LR, Olivares J, Cunningham C, Williams A, Grove W, Kraker A, Olson S, Nemunaitis J.Cancer Invest. 2004;22(6):886-96. PMID: 15641487 8:A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine. Undevia SD, Kindler HL, Janisch L, Olson SC, Schilsky RL, Vogelzang NJ, Kimmel KA, Macek TA, Ratain MJ.Ann Oncol. 2004 Nov;15(11):1705-11. PMID: 15520075 9:Phase I study of oral CI-994 in combination with gemcitabine in treatment of patients with advanced cancer. Nemunaitis JJ, Orr D, Eager R, Cunningham CC, Williams A, Mennel R, Grove W, Olson S.Cancer J. 2003 Jan-Feb;9(1):58-66. PMID: 12602769 10:Induction of Apoptosis in Rat Peripheral Blood Lymphocytes by the Anticancer Drug CI-994 (Acetyldinaline)(*). Graziano MJ, Spoon TA, Cockrell EA, Rowse PE, Gonzales AJ.J Biomed Biotechnol. 2001;1(2):52-61. PMID: 12488610 Free PMC Article