FTI-277 HCl
featured

    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.


Price and Availability

Size
Price

10mg
Ask price
100mg
Ask price
1g
Ask price
Size
Price

25mg
Ask price
200mg
Ask price
2g
Ask price
Size
Price

50mg
Ask price
500mg
Ask price
5g
Ask price

FTI-277-HCl is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

img

Theoretical Analysis

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


Technical Data

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).

Harmonized System Code:
293490


Additional Information

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.
 
 
 


References

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.