Catalog Number
ACM1247018194
Description
FGTI-2734 is a RAS C-terminal mimetic dual farnesyl transferase (FT) and geranylgeranyl transferase-1 (GGT-1) inhibitor. It can prevent membrane localization of KRAS, hence solving KRAS resistance problem and thwarting mutant KRAS patient-derived pancreatic tumors.
Synonyms
FGTI-2734; FGTI2734; FGTI 2734
IUPAC Name
N-(2-((4-cyano-2-fluorophenyl)((1-methyl-1H-imidazol-5-yl)methyl)amino)ethyl)-N-(cyclohexylmethyl)pyridine-2-sulfonamide
Molecular Formula
C26H31FN6O2S
Canonical SMILES
O=S(C1=NC=CC=C1)(N(CC2CCCCC2)CCN(CC3=CN=CN3C)C4=CC=C(C=C4F)C#N)=O
InChI
InChI=1S/C26H31FN6O2S/c1-31-20-29-17-23(31)19-32(25-11-10-22(16-28)15-24(25)27)13-14-33(18-21-7-3-2-4-8-21)36(34,35)26-9-5-6-12-30-26/h5-6,9-12,15,17,20-21H,2-4,7-8,13-14,18-19H2,1H3
InChI Key
BXNRVJLIEMQDOL-UHFFFAOYSA-N
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Storage
Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
Biological Target
FGTI-2734 is a RAS C-terminal mimetic dual farnesyl transferase (FT) and geranylgeranyl transferase-1 (GGT-1) inhibitor with IC50s of 250 nM and 520 nM for FT and GGT-1, respectively.
Drug Formulation
This drug may be formulated in DMSO
Elemental Analysis
C, 61.16; H, 6.12; F, 3.72; N, 16.46; O, 6.27; S, 6.28
HS Tariff Code
2934.99.9001
In Vitro Activity
Treatment with FGTI-2734 inhibited the farnesylation of HDJ2 and the geranylgeranylation of RAP1A in all 6 cell lines (Fig. 3). However, FGTI-2734 treatment only induced CASPASE-3 and PARP cleavage in MiaPaCa2, L3.6pl, and Calu6 cells (Figs. 3A) but not in A549, H460, and DLD1 cells (Figs. 3B), indicating that FGTI-2734 induces apoptosis only in the three cancer cell lines that are dependent on mutant KRAS for viability.
Reference: Clin Cancer Res. 2019 Oct 1; 25(19): 5984-5996. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774803/
In Vivo Activity
Compared with MiaPaCa2 tumors from vehicle control-treated mice, which grew from an average of 224 ± 50 to 1015 ± 235 mm3, tumor growth in FGTI-2734-treated mice was nearly suppressed, growing from 218 ± 22 to only 302 ± 46 mm3 (Fig. 4, top left). For the mutant KRAS-independent tumors (A549, H460, and DLD-1), FGTI-2734 had no effect on growth (Fig. 4, middle panels). Thus, although all 6 cell tumors harbor mutant KRAS, FGTI-2734 only inhibited tumor growth in mutant KRAS-dependent tumors but not in mutant KRAS-independent tumors.
Reference: Clin Cancer Res. 2019 Oct 1; 25(19): 5984-5996. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774803/
Shipping
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.
Stock Solution Storage
0-4 °C for short term (days to weeks), or -20 °C for long term (months).
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