Synonym
FGTI-2734; FGTI2734; FGTI 2734
IUPAC/Chemical Name
N-(2-((4-cyano-2-fluorophenyl)((1-methyl-1H-imidazol-5-yl)methyl)amino)ethyl)-N-(cyclohexylmethyl)pyridine-2-sulfonamide
InChi Key
BXNRVJLIEMQDOL-UHFFFAOYSA-N
InChi Code
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
SMILES Code
O=S(C1=NC=CC=C1)(N(CC2CCCCC2)CCN(CC3=CN=CN3C)C4=CC=C(C=C4F)C#N)=O
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
Shelf Life
>3 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
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.
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/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
50.0 |
97.92 |
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
510.63
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. 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.
In vitro 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.
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.
1: Kazi A, Kantilal Vasiyani HK, Ghosh D, Bandyopadhyay D, Shah RD, Vudatha V,
Trevino J, Sebti SM. FGTI-2734 Inhibits ERK Reactivation to Overcome Sotorasib
Resistance in KRAS G12C Lung Cancer. J Thorac Oncol. 2024 Nov
25:S1556-0864(24)02485-7. doi: 10.1016/j.jtho.2024.11.022. Epub ahead of print.
PMID: 39603412.
2: Dailey JM, Kee SA, Tharakan A, Kazi A, Burchett JR, Kolawole EM, Boyd
Ballance W, Kotha A, Le QT, Schwartz LB, Straus DB, Martin RK, Sebti SM, Ryan
JJ. Inhibiting Isoprenylation Suppresses FcεRI-Mediated Mast Cell Function and
Allergic Inflammation. J Immunol. 2023 Aug 15;211(4):527-538. doi:
10.4049/jimmunol.2200862. PMID: 37449905; PMCID: PMC10545418.
3: 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.
