WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406300
CAS#: 180977-34-8 (HCl)
Description: FTI-277 is a peptide mimetic of the COOH-terminal Cys-Val-Ile-Met of K-Ras4B that inhibited potently FTase in vitro (IC50 = 500 pM) and was highly selective for FTase over geranylgeranyltransferase I (GGTase I) (IC50 = 50 nM). FTI-277, the methyl ester derivative of FTI-276, was extremely potent (IC50 = 100 nM) at inhibiting H-Ras, but not the geranylgeranylated Rap1A processing in whole cells.
MedKoo Cat#: 406300
Name: FTI-277 HCl
CAS#: 180977-34-8 (HCl)
Chemical Formula: C22H30ClN3O3S2
Exact Mass:
Molecular Weight: 484.07
Elemental Analysis: C, 54.59; H, 6.25; Cl, 7.32; N, 8.68; O, 9.92; S, 13.25
Related CAS #: 170006-73-2 (free base) 180977-34-8 (HCl) 1217447-06-7 (TFA)
Synonym: FTI-277; FTI 277; FTI277; FTI-227 hydrochloride, FTI-227 HCl.
IUPAC/Chemical Name: methyl (5-(((R)-2-amino-3-mercaptopropyl)amino)-[1,1'-biphenyl]-2-carbonyl)-L-methioninate hydrochloride
InChi Key: PIAFFJUUNXEDEW-PXPMWPIZSA-N
InChi Code: InChI=1S/C22H29N3O3S2.ClH/c1-28-22(27)20(10-11-30-2)25-21(26)18-9-8-17(24-13-16(23)14-29)12-19(18)15-6-4-3-5-7-15;/h3-9,12,16,20,24,29H,10-11,13-14,23H2,1-2H3,(H,25,26);1H/t16-,20+;/m1./s1
SMILES Code: CSCC[C@@H](C(OC)=O)NC(C1=CC=C(NC[C@@H](N)CS)C=C1C2=CC=CC=C2)=O.[H]Cl
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 and in water
Shelf Life: >2 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
| Biological target: | FTI-277 hydrochloride is an inhibitor of farnesyl transferase (FTase); a highly potent Ras CAAX peptidomimetic which antagonizes both H- and K-Ras oncogenic signaling. |
| In vitro activity: | MTT assay demonstrated that FTI-277 inhibited proliferation of the H-Ras-MCF10A, Hs578T and MDA-MB-231 cells in a dose-dependent manner (Fig. 2). FTI-277 exerted a strong anti-proliferative effect on the H-Ras-MCF10A and Hs578T cells with 50% inhibitory concentration (IC50) values of 6.84 and 14.87 µM for 48 h, respectively. FTI-277 treatment inhibited proliferation of the MDA-MB-231 cells with an IC50 value of 29.32 µM for 48 h. The results suggest that breast cells in which H-Ras is activated may be more susceptible to FTI-277 compared with the cells with wild-type H-Ras. Reference: Oncol Lett. 2016 Sep;12(3):2222-2226. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998514/ |
| In vivo activity: | A single injection of farnesyltransferase inhibitor (25 mg/kg b.wt. FTI-277) at 2 h after CLP prolonged survival time of septic mice compared with vehicle alone. Kaplan-Meier survival curve analysis showed statistically significant beneficial effects of FTI-277 compared with vehicle alone (p < 0.0001) (Fig. 1A). χ2 test also revealed that FTI-277 significantly reduced mortality after CLP in mice (p = 0.001). Reference: J Pharmacol Exp Ther. 2011 Dec; 339(3): 832–841. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226365/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 98.0 | 202.45 | |
| Ethanol | 96.0 | 198.32 | |
| Water | 73.0 | 150.8 |
The following data is based on the product molecular weight 484.07 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: | 1. Ponnusamy A, Sinha S, Hyde GD, Borland SJ, Taylor RF, Pond E, Eyre HJ, Inkson CA, Gilmore A, Ashton N, Kalra PA, Canfield AE. FTI-277 inhibits smooth muscle cell calcification by up-regulating PI3K/Akt signaling and inhibiting apoptosis. PLoS One. 2018 Apr 24;13(4):e0196232. doi: 10.1371/journal.pone.0196232. PMID: 29689070; PMCID: PMC5916518. 2. Lee KH, Koh M, Moon A. Farnesyl transferase inhibitor FTI-277 inhibits breast cell invasion and migration by blocking H-Ras activation. Oncol Lett. 2016 Sep;12(3):2222-2226. doi: 10.3892/ol.2016.4837. Epub 2016 Jul 11. PMID: 27602167; PMCID: PMC4998514. 3. Li W, Tu J, Liu X, Yang W. Farnesyltransferase inhibitor FTI-277 inhibits PD-L1 expression on septic spleen lymphocytes and promotes spleen lymphocyte activation. Clin Exp Immunol. 2017 Oct;190(1):8-18. doi: 10.1111/cei.12995. Epub 2017 Jul 14. PMID: 28556912; PMCID: PMC5588849. 4. Yang W, Yamada M, Tamura Y, Chang K, Mao J, Zou L, Feng Y, Kida K, Scherrer-Crosbie M, Chao W, Ichinose F, Yu YM, Fischman AJ, Tompkins RG, Yao S, Kaneki M. Farnesyltransferase inhibitor FTI-277 reduces mortality of septic mice along with improved bacterial clearance. J Pharmacol Exp Ther. 2011 Dec;339(3):832-41. doi: 10.1124/jpet.111.183558. Epub 2011 Aug 26. PMID: 21873557; PMCID: PMC3226365. |
| In vitro protocol: | 1. Ponnusamy A, Sinha S, Hyde GD, Borland SJ, Taylor RF, Pond E, Eyre HJ, Inkson CA, Gilmore A, Ashton N, Kalra PA, Canfield AE. FTI-277 inhibits smooth muscle cell calcification by up-regulating PI3K/Akt signaling and inhibiting apoptosis. PLoS One. 2018 Apr 24;13(4):e0196232. doi: 10.1371/journal.pone.0196232. PMID: 29689070; PMCID: PMC5916518. 2. Lee KH, Koh M, Moon A. Farnesyl transferase inhibitor FTI-277 inhibits breast cell invasion and migration by blocking H-Ras activation. Oncol Lett. 2016 Sep;12(3):2222-2226. doi: 10.3892/ol.2016.4837. Epub 2016 Jul 11. PMID: 27602167; PMCID: PMC4998514. |
| In vivo protocol: | 1. Li W, Tu J, Liu X, Yang W. Farnesyltransferase inhibitor FTI-277 inhibits PD-L1 expression on septic spleen lymphocytes and promotes spleen lymphocyte activation. Clin Exp Immunol. 2017 Oct;190(1):8-18. doi: 10.1111/cei.12995. Epub 2017 Jul 14. PMID: 28556912; PMCID: PMC5588849. 2. Yang W, Yamada M, Tamura Y, Chang K, Mao J, Zou L, Feng Y, Kida K, Scherrer-Crosbie M, Chao W, Ichinose F, Yu YM, Fischman AJ, Tompkins RG, Yao S, Kaneki M. Farnesyltransferase inhibitor FTI-277 reduces mortality of septic mice along with improved bacterial clearance. J Pharmacol Exp Ther. 2011 Dec;339(3):832-41. doi: 10.1124/jpet.111.183558. Epub 2011 Aug 26. PMID: 21873557; PMCID: PMC3226365. |
1: Yang W, Yamada M, Tamura Y, Chang K, Mao J, Zou L, Feng Y, Kida K, Scherrer-Crosbie M, Chao W, Ichinose F, Yu YM, Fischman AJ, Tompkins RG, Yao S, Kaneki M. Farnesyltransferase inhibitor FTI-277 reduces mortality of septic mice along with improved bacterial clearance. J Pharmacol Exp Ther. 2011 Dec;339(3):832-41. doi: 10.1124/jpet.111.183558. Epub 2011 Aug 26. PubMed PMID: 21873557; PubMed Central PMCID: PMC3226365.
2: Kim DM, Ryu SW, Choi C. Long-term treatment of farnesyltransferase inhibitor FTI-277 induces neurotoxicity of hippocampal neurons from rat embryo in a ROS-dependent manner. Biochem Biophys Res Commun. 2010 Dec 3;403(1):91-6. doi: 10.1016/j.bbrc.2010.10.123. Epub 2010 Oct 30. PubMed PMID: 21040708.
3: Doisneau-Sixou SF, Cestac P, Faye JC, Favre G, Sutherland RL. Additive effects of tamoxifen and the farnesyl transferase inhibitor FTI-277 on inhibition of MCF-7 breast cancer cell-cycle progression. Int J Cancer. 2003 Sep 20;106(5):789-98. PubMed PMID: 12866041.
4: Girgert R, Wittrock J, Pfister S, Schweizer P. Farnesyltransferase inhibitor FTI-277 prevents autocrine growth stimulation of neuroblastoma by BDNF. J Cancer Res Clin Oncol. 2003 Apr;129(4):227-33. Epub 2003 Apr 17. PubMed PMID: 12700894.
5: Ellis CA, Vos MD, Wickline M, Riley C, Vallecorsa T, Telford WG, Zujewskil J, Clark GJ. Tamoxifen and the farnesyl transferase inhibitor FTI-277 synergize to inhibit growth in estrogen receptor-positive breast tumor cell lines. Breast Cancer Res Treat. 2003 Mar;78(1):59-67. PubMed PMID: 12611458.
6: Bolick SC, Landowski TH, Boulware D, Oshiro MM, Ohkanda J, Hamilton AD, Sebti SM, Dalton WS. The farnesyl transferase inhibitor, FTI-277, inhibits growth and induces apoptosis in drug-resistant myeloma tumor cells. Leukemia. 2003 Feb;17(2):451-7. PubMed PMID: 12592346.
7: Mazzocca A, Giusti S, Hamilton AD, Sebti SM, Pantaleo P, Carloni V. Growth inhibition by the farnesyltransferase inhibitor FTI-277 involves Bcl-2 expression and defective association with Raf-1 in liver cancer cell lines. Mol Pharmacol. 2003 Jan;63(1):159-66. PubMed PMID: 12488548.
8: Nam JS, Ino Y, Sakamoto M, Hirohashi S. Ras farnesylation inhibitor FTI-277 restores the E-cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis. Jpn J Cancer Res. 2002 Sep;93(9):1020-8. PubMed PMID: 12359056.
9: Cohen-Jonathan E, Toulas C, Ader I, Monteil S, Allal C, Bonnet J, Hamilton AD, Sebti SM, Daly-Schveitzer N, Favre G. The farnesyltransferase inhibitor FTI-277 suppresses the 24-kDa FGF2-induced radioresistance in HeLa cells expressing wild-type RAS. Radiat Res. 1999 Oct;152(4):404-11. PubMed PMID: 10477917.
10: Miquel K, Pradines A, Sun J, Qian Y, Hamilton AD, Sebti SM, Favre G. GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells. Cancer Res. 1997 May 15;57(10):1846-50. PubMed PMID: 9157972.
Treatment of H-Ras oncogene-transformed NIH 3T3 cells with FTI-277 blocked recruitment to the plasma membrane and subsequent activation of the serine/threonine kinase c-Raf-1 in cells transformed by farnesylated Ras (H-RasF), but not geranylgeranylated, Ras (H-RasGG). FTI-277 induced accumulation of cytoplasmic non-farnesylated H-Ras that was able to bind Raf and form cytoplasmic Ras/Raf complexes in which Raf kinase was not activated. Furthermore, FTI-277 blocked constitutive activation of mitogen-activated protein kinase (MAPK) in H-RasF, but not H-RasGG, or Raf-transformed cells. FTI-277 also inhibited oncogenic K-Ras4B processing and constitutive activation of MAPK, but the concentrations required were 100-fold higher than those needed for H-Ras inhibition. The results demonstrate that FTI-277 blocks Ras oncogenic signaling by accumulating inactive Ras/Raf complexes in the cytoplasm, hence preventing constitutive activation of the MAPK cascade.
