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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
GGTI-298 (GGTI298) is a potent geranylgeranyltransferase-I (GGTase-I) inhibitor with potential anticancer actrivity. GGTI-298 inhibits the G(1)-S transition and MAP kinase activation in transformed adrenocortical cells that overexpress Ki-Ras. GGTI-298 induces hypophosphorylation of retinoblastoma and partner switching of cyclin-dependent kinase inhibitors. A potential mechanism for GGTI-298 antitumor activity. Human tumor cells are stopped in G0/G1 by GGTI-298, which also causes p21(WAF1/CIP1/SDI1) to be induced without the need for p53. GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells.
| Targets |
Rap1A ( pIC50 = 3 μM ); Histamine H1 receptor ( Ha-Ras > 20 μM )
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| ln Vitro |
Both RhoA parent (GGTI298) and ROCK parent (H1152) significantly reduce cAMP agonist-stimulated IK(ap), while night also reduces the colocalization of KCNN4c with the apical membrane marker malt agglutinin in T84WT cells [1]. Knockdown of NF-κB eliminates NF-κB activation, thereby sensitizing cells to activation of DR5 induced by the combined induction of GGTI298 and TRAIL. GGTI298/TRAIL activates NF-κB and inhibits Akt. Knocking out DR5 can prevent the reduction of IκBα and p-Akt induced by GGTI298/TRAIL, indicating that DR5 mediates the reduction of IκBα and p-Akt induced by GGTI298/TRAIL. In contrast, DR4 knockdown further promotes GGTI298/TRAIL-induced p-Akt reduction [2].
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| ln Vivo |
In vivo model ileal loop experiments showed that when TRAM-34, GGTI298 or H1152 were injected into the loop together with cholera toxin, fluid volume concentration was reduced in a dose-dependent manner [1].
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| Enzyme Assay |
The specified cells are lysed in Reporter Lysis Buffer and then put through a luciferase activity assay in a luminometer using the Luciferase Assay System. The relative luciferase activity is calibrated to the protein concentration.
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| Cell Assay |
In 96-well cell culture plates, cells are seeded, and the following day, they are treated with the specified agents. The sulforhodamine B assay is used to calculate the number of viable cells.
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| Animal Protocol |
Mice aged 6 to 8 weeks are used in the ileal loop experiment, which uses a modified rabbit ileal loop assay. The animals are gut sterilized, fed only water ad libitum, and fasted for twenty-four hours before surgery. A combination of xylazine (5 mg/kg body weight) and ketamine (35 mg/kg body weight) is used to induce anesthesia. A laparotomy is done, and non-absorbable silk is used to tie the 5-cm-long experimental loops at the terminal ileum. Each loop is filled with the following fluids using a tuberculin syringe equipped with a disposable needle through the ligated end of the loop as the ligature is tightened: pure CT (1 μg; positive control), saline (negative control), CT (1 μg) + TRAM-34 (varying concentrations in μM as shown in Fig. 7), CT (1 μg) + H1152 (1 μM), and CT (1 μg) + GGTI298 (variable concentrations in μM), a specific inhibitor of Rap1A. The mice are sutured back into their cages and the intestine is reattached to the peritoneum. After six hours, the loops are removed and the animals are sacrificed by cervical dislocation. The fluid from every loop is collected, and the ratio of the fluid volume inside the loop to its length (fluid accumulation ratio in g/cm) is computed to show how effective different inhibitors are.
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| References |
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| Molecular Formula |
C27H33N3O3S
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|---|---|
| Molecular Weight |
479.634
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| Exact Mass |
479.22
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| Elemental Analysis |
C, 67.61; H, 6.93; N, 8.76; O, 10.01; S, 6.69
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| CAS # |
180977-44-0
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| Related CAS # |
GGTI298 Trifluoroacetate; 1217457-86-7
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| Appearance |
White solid powder
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| SMILES |
CC(C)C[C@@H](C(=O)OC)NC(=O)C1=C(C=C(C=C1)NC[C@H](CS)N)C2=CC=CC3=CC=CC=C32
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| InChi Key |
XVWPFYDMUFBHBF-CLOONOSVSA-N
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| InChi Code |
InChI=1S/C27H33N3O3S/c1-17(2)13-25(27(32)33-3)30-26(31)23-12-11-20(29-15-19(28)16-34)14-24(23)22-10-6-8-18-7-4-5-9-21(18)22/h4-12,14,17,19,25,29,34H,13,15-16,28H2,1-3H3,(H,30,31)/t19-,25+/m1/s1
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| Chemical Name |
methyl (2S)-2-[[4-[[(2R)-2-amino-3-sulfanylpropyl]amino]-2-naphthalen-1-ylbenzoyl]amino]-4-methylpentanoate
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| Synonyms |
GGTI 298; GGTI298; GGTI-298
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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 Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0849 mL | 10.4247 mL | 20.8494 mL | |
| 5 mM | 0.4170 mL | 2.0849 mL | 4.1699 mL | |
| 10 mM | 0.2085 mL | 1.0425 mL | 2.0849 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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