BMS-214662
BMS-214662 is a Farnesyltransferase inhibitor , is also a nonsedating benzodiazepine derivative with potential antineoplastic activity. BMS-214662 inhibits the enzyme farnesyltransferase and the post-translational farnesylation of number of proteins involved in signal transduction, which may result in the inhibition of Ras function and apoptosis in susceptible tumor cells. This agent may reverse the malignant phenotype of H-Ras-transformed cells and has been shown to be active against tumor cells with and without Ras mutations.
1: Balabanov S, Evans CA, Abraham SA, Pellicano F, Copland M, Walker MJ, Whetton AD, Holyoake TL. Quantitative proteomics analysis of BMS-214662 effects on CD34 positive cells from chronic myeloid leukaemia patients. Proteomics. 2013 Jan;13(1):153-68. doi: 10.1002/pmic.201200022. PubMed PMID: 23184491.
2: Pellicano F, Simara P, Sinclair A, Helgason GV, Copland M, Grant S, Holyoake TL. The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells. Leukemia. 2011 Jul;25(7):1159-67. doi: 10.1038/leu.2011.67. Epub 2011 Apr 12. PubMed PMID: 21483442.
3: Nassar MN, Cucolo M, Miller SA. Ethyl methanesulphonate in a parenteral formulation of BMS-214662 mesylate, a selective farnesyltransferase inhibitor: formation and rate of hydrolysis. Pharm Dev Technol. 2009;14(6):672-7. doi: 10.3109/10837450902980262. PubMed PMID: 19883257.
4: Pellicano F, Copland M, Jorgensen HG, Mountford J, Leber B, Holyoake TL. BMS-214662 induces mitochondrial apoptosis in chronic myeloid leukemia (CML) stem/progenitor cells, including CD34+38- cells, through activation of protein kinase Cbeta. Blood. 2009 Nov 5;114(19):4186-96. doi: 10.1182/blood-2009-05-219550. Epub 2009 Sep 8. PubMed PMID: 19738029.
5: Copland M, Pellicano F, Richmond L, Allan EK, Hamilton A, Lee FY, Weinmann R, Holyoake TL. BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors. Blood. 2008 Mar 1;111(5):2843-53. Epub 2007 Dec 21. Erratum in: Blood. 2008 May 1;111(9):4830. PubMed PMID: 18156496.
6: Bailey HH, Alberti DB, Thomas JP, Mulkerin DL, Binger KA, Gottardis MM, Martell RE, Wilding G. Phase I trial of weekly paclitaxel and BMS-214662 in patients with advanced solid tumors. Clin Cancer Res. 2007 Jun 15;13(12):3623-9. Epub 2007 May 17. PubMed PMID: 17510207.
7: Eder JP Jr, Ryan DP, Appleman L, Zhu AX, Puchalski T, He X, Sonnichsen DS, Cooper M, Wright J, Clark JW, Supko JG. Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 administered as a weekly 24 h continuous intravenous infusion in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2006 Jul;58(1):107-16. Epub 2005 Dec 13. PubMed PMID: 16362299.
8: Papadimitrakopoulou V, Agelaki S, Tran HT, Kies M, Gagel R, Zinner R, Kim E, Ayers G, Wright J, Khuri F. Phase I study of the farnesyltransferase inhibitor BMS-214662 given weekly in patients with solid tumors. Clin Cancer Res. 2005 Jun 1;11(11):4151-9. PubMed PMID: 15930351.
9: Dy GK, Bruzek LM, Croghan GA, Mandrekar S, Erlichman C, Peethambaram P, Pitot HC, Hanson LJ, Reid JM, Furth A, Cheng S, Martell RE, Kaufmann SH, Adjei AA. A phase I trial of the novel farnesyl protein transferase inhibitor, BMS-214662, in combination with paclitaxel and carboplatin in patients with advanced cancer. Clin Cancer Res. 2005 Mar 1;11(5):1877-83. PubMed PMID: 15756013.
10: Gómez-Benito M, Marzo I, Anel A, Naval J. Farnesyltransferase inhibitor BMS-214662 induces apoptosis in myeloma cells through PUMA up-regulation, Bax and Bak activation, and Mcl-1 elimination. Mol Pharmacol. 2005 Jun;67(6):1991-8. Epub 2005 Feb 28. PubMed PMID: 15738311.
2: Pellicano F, Simara P, Sinclair A, Helgason GV, Copland M, Grant S, Holyoake TL. The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells. Leukemia. 2011 Jul;25(7):1159-67. doi: 10.1038/leu.2011.67. Epub 2011 Apr 12. PubMed PMID: 21483442.
3: Nassar MN, Cucolo M, Miller SA. Ethyl methanesulphonate in a parenteral formulation of BMS-214662 mesylate, a selective farnesyltransferase inhibitor: formation and rate of hydrolysis. Pharm Dev Technol. 2009;14(6):672-7. doi: 10.3109/10837450902980262. PubMed PMID: 19883257.
4: Pellicano F, Copland M, Jorgensen HG, Mountford J, Leber B, Holyoake TL. BMS-214662 induces mitochondrial apoptosis in chronic myeloid leukemia (CML) stem/progenitor cells, including CD34+38- cells, through activation of protein kinase Cbeta. Blood. 2009 Nov 5;114(19):4186-96. doi: 10.1182/blood-2009-05-219550. Epub 2009 Sep 8. PubMed PMID: 19738029.
5: Copland M, Pellicano F, Richmond L, Allan EK, Hamilton A, Lee FY, Weinmann R, Holyoake TL. BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors. Blood. 2008 Mar 1;111(5):2843-53. Epub 2007 Dec 21. Erratum in: Blood. 2008 May 1;111(9):4830. PubMed PMID: 18156496.
6: Bailey HH, Alberti DB, Thomas JP, Mulkerin DL, Binger KA, Gottardis MM, Martell RE, Wilding G. Phase I trial of weekly paclitaxel and BMS-214662 in patients with advanced solid tumors. Clin Cancer Res. 2007 Jun 15;13(12):3623-9. Epub 2007 May 17. PubMed PMID: 17510207.
7: Eder JP Jr, Ryan DP, Appleman L, Zhu AX, Puchalski T, He X, Sonnichsen DS, Cooper M, Wright J, Clark JW, Supko JG. Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 administered as a weekly 24 h continuous intravenous infusion in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2006 Jul;58(1):107-16. Epub 2005 Dec 13. PubMed PMID: 16362299.
8: Papadimitrakopoulou V, Agelaki S, Tran HT, Kies M, Gagel R, Zinner R, Kim E, Ayers G, Wright J, Khuri F. Phase I study of the farnesyltransferase inhibitor BMS-214662 given weekly in patients with solid tumors. Clin Cancer Res. 2005 Jun 1;11(11):4151-9. PubMed PMID: 15930351.
9: Dy GK, Bruzek LM, Croghan GA, Mandrekar S, Erlichman C, Peethambaram P, Pitot HC, Hanson LJ, Reid JM, Furth A, Cheng S, Martell RE, Kaufmann SH, Adjei AA. A phase I trial of the novel farnesyl protein transferase inhibitor, BMS-214662, in combination with paclitaxel and carboplatin in patients with advanced cancer. Clin Cancer Res. 2005 Mar 1;11(5):1877-83. PubMed PMID: 15756013.
10: Gómez-Benito M, Marzo I, Anel A, Naval J. Farnesyltransferase inhibitor BMS-214662 induces apoptosis in myeloma cells through PUMA up-regulation, Bax and Bak activation, and Mcl-1 elimination. Mol Pharmacol. 2005 Jun;67(6):1991-8. Epub 2005 Feb 28. PubMed PMID: 15738311.
| Chemical | |
|---|---|
| CAS Num | 195987-41-8 (free base) |
| Chemical Formula | C25H23N5O2S2 |
| Molecular Weight | 489.61 |
| IUPAC Chemical Name | (R)-1-((1H-imidazol-5-yl)methyl)-3-benzyl-4-(thiophen-2-ylsulfonyl)-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine-7-carbonitrile |
| Exact Mass | 489.12932 |
| Elemental Analysis | C, 61.33; H, 4.73; N, 14.30; O, 6.54; S, 13.10 |
| Synonym | ARQ171; ARQ 171; ARQ-171; BMS214662; BMS214662; BMS-214662 |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | N#CC1=CC=C2N(CC3=CN=CN3)C[C@@H](CC4=CC=CC=C4)N(S(=O)(C5=CC=CS5)=O)CC2=C1 |
| Biological | |
| Targets and Effects | farnesyltransferase inhibitor |
| Pathways | Apoptosis |
| Physical | |
| 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). |
| Shelf Life | >5 years if stored properly |
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