FTI 277 HCl |
| Katalog-Nr.GC16310 |
FTI 277 HCl ist ein Inhibitor der Farnesyltransferase (FTase); ein hochpotentes Ras-CAAX-Peptidomimetikum, das sowohl die onkogene H- als auch die K-Ras-Signalgebung antagonisiert.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 180977-34-8
Sample solution is provided at 25 µL, 10mM.
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FTI 277 HCl is a potent and selective farnesyltransferase (FTase) inhibitor with an IC50 value of 0.5nM, exhibiting approximately 100-fold greater selectivity over geranylgeranyltransferase I (GGTase I)[1]. FTase-mediated farnesylation is the first irreversible and rate-limiting step for Ras membrane association, and is an obligatory modification for the biological activity of oncogenic Ras[2]. FTI 277 HCl is commonly used in research on the function of farnesyltransferase and the role of Ras-mediated signaling pathways in diseases such as cancer[3,4].
In vitro, treatment of vascular smooth muscle cells (VSMCs) with FTI 277 HCl (20μM) for 10 days significantly inhibited β-glycerophosphate (βGP)-induced mineral deposition, reduced the mRNA expression of Runx2 and Msx2, and up-regulated the expression of MGP[5]. Pretreatment of breast cancer MDA-MB-231 cells with FTI 277 HCl (50μM) for 24h inhibited epidermal growth factor (EGF)-induced activation of H-Ras in the membrane fraction, but did not inhibit the activation of N-Ras[6].
In vivo, administration of FTI 277 HCl (1 and 5mg/kg/day) via intraperitoneal injection in SCID mice inoculated with human colon cancer HT29 cells for 3 weeks significantly reduced relative spleen weight and primary splenic tumor volume, as well as relative liver weight and liver metastasis volume, without causing significant toxicity[7]. In mice treated with FTI 277 HCl (25mg/kg) via intraperitoneal injection before L-arginine-induced pancreatitis, samples were harvested 72h after the first dose of L-arginine. FTI 277 HCl administration significantly reduced L-arginine-induced myeloperoxidase (MPO) levels and the number of extravascular neutrophils in the pancreas[8].
References:
[1] LERNER E C, QIAN Y, BLASKOVICH M A, et al. Ras CAAX peptidomimetic FTI-277 selectively blocks oncogenic Ras signaling by inducing cytoplasmic accumulation of inactive Ras-Raf complexes[J]. Journal of Biological Chemistry, 1995, 270(45): 26802-26806.
[2] COX A D, DER C J, PHILIPS M R. Targeting RAS membrane association: back to the future for anti-RAS drug discovery?[J]. Clinical Cancer Research, 2015, 21(8): 1819-1827.
[3] MAZZOCCA A, GIUSTI S, HAMILTON A D, et al. Growth inhibition by the farnesyltransferase inhibitor FTI-277 involves Bcl-2 expression and defective association with Raf-1 in liver cancer cell lines[J]. Molecular Pharmacology, 2003, 63(1): 159-166.
[4] BERNHARD E J, KAO G, COX A D, et al. The farnesyltransferase inhibitor FTI-277 radiosensitizes H-ras-transformed rat embryo fibroblasts[J]. Cancer Research, 1996, 56(8): 1727-1730.
[5] PONNUSAMY A, SINHA S, HYDE G D, et al. FTI-277 inhibits smooth muscle cell calcification by up-regulating PI3K/Akt signaling and inhibiting apoptosis[J]. PLoS One, 2018, 13(4): e0196232.
[6] LEE K H, KOH M, MOON A. Farnesyl transferase inhibitor FTI-277 inhibits breast cell invasion and migration by blocking H-Ras activation[J]. Oncology Letters, 2016, 12(3): 2222-2226.
[7] NAM J S, INO Y, SAKAMOTO M, et al. Ras farnesylation inhibitor FTI-277 restores the E-cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis[J]. Japanese Journal of Cancer Research, 2002, 93(9): 1020-1028.
[8] MERZA M, AWLA D, HWAIZ R, et al. Farnesyltransferase regulates neutrophil recruitment and tissue damage in acute pancreatitis[J]. Pancreas, 2014, 43(3): 427-435.
| Cell experiment [1]: | |
Cell lines | MDA-MB-231 (breast cancer cells) |
Preparation Method | H-Ras and N-Ras are mainly located on the inner side of the cell membrane. To collect membrane fractions, cells were treated with FTI 277 HCl (50µM) for 24h and EGF (10ng/ml) for 30min prior to lysis. |
Reaction Conditions | 50μM; 24h |
Applications | FTI 277 HCl inhibited the EGF-induced activation of H-Ras, but not that of N-Ras, in membrane fractions of MDA-MB-231 cells. |
| Animal experiment [2]: | |
Animal models | SCID mice inoculated with HT29 cells |
Preparation Method | HT29 cells (1.5 × 106 cells) were inoculated into the spleen of SCID mice. After inoculation, FTI 277 HCl (1 and 5mg/kg/day) was administered daily for 3 weeks i.p. to SCID mice. |
Dosage form | 1 and 5mg/kg/day; 3 weeks; i.p. |
Applications | FTI 277 HCl treatment significantly reduced relative spleen weight and splenic primary tumor volume and also significantly reduced relative liver weight and liver metastasis volume. And no toxicity (diarrhea or loss of body weight) was detected in the FTI 277 HCl treatment group. |
References: | |
| Cas No. | 180977-34-8 | SDF | |
| Chemical Name | (Z)-5-(((R)-2-amino-3-mercaptopropyl)amino)-N-((S)-1-methoxy-4-(methylthio)-1-oxobutan-2-yl)-[1,1'-biphenyl]-2-carbimidic acid hydrochloride | ||
| Canonical SMILES | COC([C@](/N=C(O)/C1=C(C2=CC=CC=C2)C=C(NC[C@](N)([H])CS)C=C1)([H])CCSC)=O.Cl | ||
| Formula | C22H30ClN3O3S2 | M.Wt | 484.07 |
| Löslichkeit | ≥ 100mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0658 mL | 10.3291 mL | 20.6582 mL |
| 5 mM | 413.2 μL | 2.0658 mL | 4.1316 mL |
| 10 mM | 206.6 μL | 1.0329 mL | 2.0658 mL |
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Quality Control & SDS
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- Purity: >99.00%
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Average Rating: 5 (Based on Reviews and 7 reference(s) in Google Scholar.)
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