FTI-2148 | CAS#251577-09-0 | farnesyltransferase inhibitor

MedKoo Cat#: 406425 | Name: FTI-2148 free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

FTI-2148 is a potent farnesyltransferase inhibitor with potential antitumor activity. FTI-2148 is highly selective for FTase (IC50, 1.4 nM) over GGTase I (IC50, 1700 nM). FTI-2148 suppressed the growth of the human lung adenocarcinoma A-549 cells in nude mice by 33, 67, and 91% in a dose-dependent manner. Combination therapy of FTI-2148 with either cisplatin, gemcitabine, or Taxol resulted in a greater antitumor efficacy than monotherapy.

Chemical Structure

FTI-2148 free base

CAS#251577-09-0 (free base)

Theoretical Analysis

MedKoo Cat#: 406425

Name: FTI-2148 free base

CAS#: 251577-09-0 (free base)

Chemical Formula: C24H28N4O3S

Exact Mass: 452.1882

Molecular Weight: 452.57

Elemental Analysis: C, 63.69; H, 6.24; N, 12.38; O, 10.61; S, 7.08

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 550.00	Ready to ship
50mg	USD 950.00	Ready to ship
100mg	USD 1,650.00	Ready to ship
200mg	USD 2,850.00	Ready to ship

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Related CAS #

817586-01-9 (TFA) 251577-09-0 (free base)

Synonym

FTI2148; FTI 2148; FTI-2148; FTI-2148 TFA; FTI-2148 trfluoroacetic acid salt; FTI-2148 free base

IUPAC/Chemical Name

(5-((((1H-imidazol-4-yl)methyl)amino)methyl)-2'-methyl-[1,1'-biphenyl]-2-carbonyl)-L-methionine

InChi Key

KULAYTGUTXCHSV-QFIPXVFZSA-N

InChi Code

InChI=1S/C24H28N4O3S/c1-16-5-3-4-6-19(16)21-11-17(12-25-13-18-14-26-15-27-18)7-8-20(21)23(29)28-22(24(30)31)9-10-32-2/h3-8,11,14-15,22,25H,9-10,12-13H2,1-2H3,(H,26,27)(H,28,29)(H,30,31)/t22-/m0/s1

SMILES Code

CSCC[C@H](NC(C1=CC=C(C=C1C2=CC=CC=C2C)CNCC3=CNC=N3)=O)C(O)=O

Appearance

white 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, not 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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#YXM200702

QC Data

View QC data: current batch, Lot#YXM200702

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

FTI-2148 is a RAS C-terminal mimetic dual farnesyl transferase (FT-1) and geranylgeranyl transferase-1 (GGT-1) inhibitor with IC50s of 1.4 nM and 1.7 μM, respectively.

In vitro activity:

To determine the potency and selectivity of FTI-2148, its ability to inhibit the transfer of farnesyl from [3H]FPP and [3H]GGPP to HRas CVLS and H-Ras CVLL, respectively, was evaluated. Table 1 shows IC50s of the inhibitors. FTI-2148 (IC50, 1.4 nm) is 2.5 times more potent than GGTI-297 (IC50, 55 nm). Table 1 also shows that FTI-2148 (1200-fold) is highly selective for FTase over GGTase. hus, for FTIs, replacement of reduced cysteine by the imidazole derivative and the phenyl substituent by tolyl (Fig. 1) resulted in much higher selectivity with little loss of potency. Although FTI-2148 alone was capable of inhibiting human tumor growth, drug removal resulted in tumor regrowth. Reference: Cancer Res. 1999 Oct 1;59(19):4919-26. https://cancerres.aacrjournals.org/content/59/19/4919.long

In vivo activity:

To evaluate the effects of replacing the reduced cysteine by an imidazole derivative and the phenyl group by a tolyl, the antitumor potency of FTI-2148 and FTI-276 (both i.p. and s.c. delivery) were compared in the human lung adenocarcinoma A-549 cell nude mouse model. Fig. 5 A ⇓ shows that, over a period of 83 days, tumors from animals that were treated with vehicle reached an average size of 839.56 ± 162.66 mm3, whereas those treated with FTI-276 or FTI-2148 grew to average sizes of 193.21 ± 61.88 mm3 or 122.95 ± 17.36 mm3, respectively. Thus, FTI-276 and FTI-2148 inhibited A-549 tumor growth by 82 and 91%, respectively. This suggested that the effect of FTI-276 and FTI-2148 on A-549 tumor growth in nude mice is cytostatic. To confirm this, A-549 cellbearing nude mice were treated with FTI-276 or FTI-2148 (25 mpk/day for 14 days) and followed tumor growth for an additional 15 days after drug cessation. Fig. 5B ⇓ shows that FTI-276 and FTI-2148 delivered via s.c. mini-pumps at a rate of 25 mpk/day for 14 days inhibited tumor growth by 50 and 77%, respectively, by the end of the 2-week treatment. Furthermore, after drug treatment was stopped, the tumors from the FTI-276 group grew faster than those from the FTI-2148 group. Thus, the data show that FTI-2148 is more effective than FTI-276. Reference: Cancer Res. 1999 Oct 1;59(19):4919-26. https://cancerres.aacrjournals.org/content/59/19/4919.long

	Solvent	mg/mL	mM
Solubility
	DMSO	0.0	0.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 452.57 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. Sun J, Blaskovich MA, Knowles D, Qian Y, Ohkanda J, Bailey RD, Hamilton AD, Sebti SM. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res. 1999 Oct 1;59(19):4919-26. PMID: 10519405. 2. Kazi A, Xiang S, Yang H, Chen L, Kennedy P, Ayaz M, Fletcher S, Cummings C, Lawrence HR, Beato F, Kang Y, Kim MP, Delitto A, Underwood PW, Fleming JB, Trevino JG, Hamilton AD, Sebti SM. Dual Farnesyl and Geranylgeranyl Transferase Inhibitor Thwarts Mutant KRAS-Driven Patient-Derived Pancreatic Tumors. Clin Cancer Res. 2019 Oct 1;25(19):5984-5996. doi: 10.1158/1078-0432.CCR-18-3399. Epub 2019 Jun 21. PMID: 31227505; PMCID: PMC6774803. 3. Sun J, Ohkanda J, Coppola D, Yin H, Kothare M, Busciglio B, Hamilton AD, Sebti SM. Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice. Cancer Res. 2003 Dec 15;63(24):8922-9. PMID: 14695209.

In vitro protocol:

In vivo protocol:

1: Kazi A, Xiang S, Yang H, Chen L, Kennedy P, Ayaz M, Fletcher S, Cummings C, Lawrence HR, Beato F, Kang Y, Kim MP, Delitto A, Underwood PW, Fleming JB, Trevino JG, Hamilton AD, Sebti SM. Dual Farnesyl and Geranylgeranyl Transferase Inhibitor Thwarts Mutant KRAS-Driven Patient-Derived Pancreatic Tumors. Clin Cancer Res. 2019 Oct 1;25(19):5984-5996. doi: 10.1158/1078-0432.CCR-18-3399. Epub 2019 Jun 21. PMID: 31227505; PMCID: PMC6774803. 2: Guida WC, Hamilton AD, Crotty JW, Sebti SM. Protein farnesyltransferase: flexible docking studies on inhibitors using computational modeling. J Comput Aided Mol Des. 2005 Dec;19(12):871-85. doi: 10.1007/s10822-005-9030-2. Epub 2006 May 12. PMID: 16607571. 3: Carrico D, Ohkanda J, Kendrick H, Yokoyama K, Blaskovich MA, Bucher CJ, Buckner FS, Van Voorhis WC, Chakrabarti D, Croft SL, Gelb MH, Sebti SM, Hamilton AD. In vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability. Bioorg Med Chem. 2004 Dec 15;12(24):6517-26. doi: 10.1016/j.bmc.2004.09.020. PMID: 15556768. 4: Sun J, Ohkanda J, Coppola D, Yin H, Kothare M, Busciglio B, Hamilton AD, Sebti SM. Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice. Cancer Res. 2003 Dec 15;63(24):8922-9. PMID: 14695209. 5: Sun J, Blaskovich MA, Knowles D, Qian Y, Ohkanda J, Bailey RD, Hamilton AD, Sebti SM. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res. 1999 Oct 1;59(19):4919-26. PMID: 10519405.