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Purity: ≥98%
FGTI-2734 (FGTI2734) is a novel and potent RAS C-terminal mimetic, acting as a dual farnesyl transferase (FT) and geranylgeranyl transferase-1 (GGT) inhibitor that thwarts Mutant KRAS-Driven Patient-Derived Pancreatic Tumors with IC50s of 250 nM and 520 nM for FT and GGT, respectively. FGTI-2734 can prevent membrane localization of KRAS, hence solving KRAS resistance problem and thwarting mutant KRAS patient-derived pancreatic tumors. Mutant KRAS is a major driver of pancreatic oncogenesis and therapy resistance, yet KRAS inhibitors are lacking in the clinic. KRAS requires farnesylation for membrane localization and cancer-causing activity prompting the development of farnesyltransferase inhibitors (FTIs) as anticancer agents. However, KRAS becomes geranylgeranylated and active when cancer cells are treated with FTIs. To overcome this geranylgeranylation-dependent resistance to FTIs, we designed FGTI-2734, a RAS C-terminal mimetic dual FT and geranylgeranyltransferase-1 inhibitor (GGTI)
| ln Vitro |
CASPASE-3 and PARP cleavage are induced in MiaPaCa2, L3.6pl, and Calu6 cells by FGTI-2734 (1-30 μM; 72 hours) [1]. HDJ2, RAP1A, KRAS, and NRAS protein prenylation is inhibited by FGTI-2734 (3-30 μM; 72 hours). In RAS-transformed murine NIH3T3 cells and mutant KRAS human cancer cells, FGTI-2734 suppresses KRAS membrane localization [1].
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| ln Vivo |
Only mutant KRAS-dependent tumors are inhibited by FGTI-2734 (intraperitoneal injection; 100 mg/kg daily for 18 to 25 days)—mutant KRAS-independent tumors are not [1].
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| Cell Assay |
Apoptosis analysis[1]
Cell Types: MiaPaCa2, L3.6pl and Calu6 Cell Tested Concentrations: 1, 3, 10, 30 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induction of CASPASE-3 and PARP cleavage. Western Blot Analysis[1] Cell Types: NIH3T3 cells transformed with KRAS, HRAS and NRAS Tested Concentrations: 3, 10, 30 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of protein prenylation of HDJ2, RAP1A, KRAS and NRAS. |
| Animal Protocol |
Animal/Disease Models: Male SCID-bg mice injected with MiaPaCa2, L3.6pl, Calu6, A549, H460 and DLD1 cancer cells [1]
Doses: 100 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; continued for 18 to 25-day Experimental Results: Inhibition of tumor growth in tumors with KRAS-dependent mutations. |
| References |
[1]. Kazi A, et al. Dual farnesyl and geranylgeranyl transferase inhibitor thwarts mutant KRAS-driven patient-derived pancreatic tumors. Clin Cancer Res. 2019 Jun 21.
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| Molecular Formula |
C26H31FN6O2S
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| Molecular Weight |
510.626747369766
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| CAS # |
1247018-19-4
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| Related CAS # |
FGTI-2734 mesylate;2702297-24-1
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| SMILES |
O=S(C1=NC=CC=C1)(N(CCN(C2=CC=C(C#N)C=C2F)CC3=CN=CN3C)CC4CCCCC4)=O
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| Synonyms |
FGTI2734; FGTI-2734; FGTI 2734
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~97.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (14.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 75.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9584 mL | 9.7918 mL | 19.5837 mL | |
| 5 mM | 0.3917 mL | 1.9584 mL | 3.9167 mL | |
| 10 mM | 0.1958 mL | 0.9792 mL | 1.9584 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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