| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
GGTase I (IC50 = 9.5 nM); FTase (IC50 = 53 μM)
GGTI-2418 targets geranylgeranyltransferase I (GGTase I), an enzyme that catalyzes the transfer of a geranylgeranyl group from geranylgeranyl pyrophosphate to a cysteine residue in the C-terminal CAAX motif of target proteins. By inhibiting GGTase I, the compound blocks the geranylgeranylation of proteins such as Rho, Rac, and Rab GTPases, which are involved in cell proliferation, migration, and cytoskeletal organization. |
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| ln Vitro |
GGTI-2418 inhibits GGTase I and FTase activities with IC50s of 9.5±2.0 nM and 53±11 μM, respectively, a 5,600-fold selectivity toward inhibition of GGTase I versus FTase. With a Ki of 4.4±1.6 nM, GGTI-2418 exhibits competitive inhibition of GGTase I against the H-Ras-CVLL protein[1]. Treatment with GGTi-2418 (10–15 μM; 16 hours) delocalizes FBXL2 and stabilizes IP3R3[2].
In vitro, GGTI-2418 potently inhibits geranylgeranyltransferase I activity. The compound's inhibitory potency has been characterized in enzymatic assays using purified GGTase I and appropriate substrates. By blocking geranylgeranylation, GGTI-2418 prevents the membrane localization and function of geranylgeranylated proteins. Its effects on cell proliferation, migration, and signaling have been studied in various cell types. |
| ln Vivo |
GGTI-2418 (100 mg/kg daily or 200 mg/kg every third day; 15 days) significantly slows the growth of breast tumor xenografts in nude mice with MDA-MB-231 xenografts[1].
In ErbB2 transgenic mice, GGTI-2418 (100 mg/kg daily; 5 days) causes the regression of mammary tumors that are driven by ErbB2[1]. The phosphorylation of Akt at S473 is significantly reduced as a result of GGTI-2418's inhibition of Rap1's geranylgeranylation. In vivo, p27 levels are also increased by GGTI-2418[1]. In vivo, GGTI-2418 has been used to study the role of geranylgeranylation in various physiological and pathological processes. By inhibiting GGTase I, the compound modulates the function of Rho, Rac, and other geranylgeranylated proteins in animal models. Its effects on tumor growth, inflammation, and other GGTase I-related processes have been investigated. Specific dosing regimens and detailed efficacy data are available in the scientific literature. |
| Enzyme Assay |
In vitro enzyme assays for GGTI-2418 involve measuring the inhibition of geranylgeranyltransferase I activity using purified enzyme preparations. The compound is incubated with GGTase I, geranylgeranyl pyrophosphate, and a peptide substrate representing the CAAX motif of a target protein. The transfer of the geranylgeranyl group to the peptide is measured using radiometric or fluorescence-based detection methods. The IC50 value is determined from dose-response curves.
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| Cell Assay |
In vitro cell-based assays for GGTI-2418 involve treating cells with the compound to assess its effects on protein geranylgeranylation, cell proliferation, and signaling. Protein geranylgeranylation is assessed by metabolic labeling or Western blotting using antibodies specific for geranylgeranylated proteins. Cell proliferation is measured using MTT or similar assays. Signaling pathway modulation (e.g., Rho, Rac, MAPK) is analyzed by Western blotting. These assays characterize the compound's cellular effects.
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| Animal Protocol |
Nude mice implanted with MDA-MB-231 breast cancer tumors[1]
100 mg/kg daily or 200 mg/kg every third day Injected intraperitoneally; 15 days In vivo animal experiments for GGTI-2418 have been conducted in models of cancer, inflammation, and other GGTase I-related conditions. Tumor-bearing mice are treated with GGTI-2418, and tumor growth inhibition is monitored. Effects on Rho and Rac signaling are assessed in tissues. Efficacy endpoints depend on the specific model being studied. These studies have helped elucidate the role of geranylgeranylation in various disease states. |
| ADME/Pharmacokinetics |
GGTI-2418 is a cell-permeable inhibitor of geranylgeranyltransferase I. The compound's molecular weight and formula are consistent with its chemical structure. It is typically dissolved in DMSO for in vitro studies and formulated for in vivo administration. Specific pharmacokinetic data such as absorption, distribution, metabolism, and elimination are not extensively reported. The compound is typically stored under recommended conditions for research compounds.
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| Toxicity/Toxicokinetics |
Specific toxicity data for GGTI-2418 is not extensively reported. As a GGTase I inhibitor, its safety profile is related to its effects on geranylgeranylation-dependent protein function. The compound is generally well-tolerated in preclinical studies at concentrations used for GGTase I inhibition. Comprehensive toxicological studies would be required for therapeutic development. Standard safety precautions should be taken when handling the compound in research settings.
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| References |
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| Additional Infomation |
PTX-100, a geranylgeranyltransferase I inhibitor, is a small-molecule synthetic peptide mimic that inhibits the protein geranylgeranyltransferase type I (GGTase-I; GGT-1) and possesses potential antitumor activity. After administration, PTX-100 targets and binds to GGTase-I, an enzyme involved in the post-translational modification of various oncogenic GTPases, including K-Ras, N-Ras, RhoA, RhoC, Cdc42, RalA, RalB, Rap1, and Rac1. Inhibition of geranylgeranylation (GG) inhibits the post-translational modification of these oncogenic proteins, thereby suppressing their membrane localization and oncogenic activity. This blocks Ras-mediated signaling and inhibits Ras-mediated cancer cell proliferation, migration, invasion, and metastasis. This may lead to cell cycle arrest and induce apoptosis. Furthermore, PTX-100 may downregulate several other activated cancer survival pathways. Geraniylgeraniylation of proteins catalyzed by GGTase-I plays a crucial role in malignant transformation and cancer cell proliferation, migration, and invasion. GGTI-2418 is a small molecule drug currently in Phase I clinical trials (covering all indications) and has two investigational indications.
GGTI-2418 is a potent inhibitor of geranylgeranyltransferase I (GGTase I) used in research to study protein geranylgeranylation. By blocking GGTase I, the compound prevents the geranylgeranylation of Rho, Rac, and other GTPases, affecting cell proliferation, migration, and signaling. GGTI-2418 is a valuable tool for studying the role of geranylgeranylation in cell biology and disease. |
| Molecular Formula |
C23H31N5O4
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|---|---|
| Molecular Weight |
441.52
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| Exact Mass |
441.238
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| Elemental Analysis |
C, 62.57; H, 7.08; N, 15.86; O, 14.49
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| CAS # |
501010-06-6
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| Related CAS # |
501010-05-5;501010-06-6 (free acid);1044590-78-4 (sodium);
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| PubChem CID |
11539477
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| Appearance |
Solid powder
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| LogP |
2.262
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
32
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| Complexity |
667
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C1[C@]([H])(C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])N(C(N([H])[C@]([H])(C(=O)O[H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)C([H])([H])C([H])([H])N1C([H])([H])C1=C(C([H])([H])[H])N([H])C([H])=N1
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| InChi Key |
COLCNDRDBCLVOC-ICSRJNTNSA-N
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| InChi Code |
InChI=1S/C23H31N5O4/c1-15(2)11-18(22(30)31)26-23(32)28-10-9-27(13-19-16(3)24-14-25-19)21(29)20(28)12-17-7-5-4-6-8-17/h4-8,14-15,18,20H,9-13H2,1-3H3,(H,24,25)(H,26,32)
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| Chemical Name |
(2S)-2-[[(2S)-2-benzyl-4-[(5-methyl-1H-imidazol-4-yl)methyl]-3-oxopiperazine-1-carbonyl]amino]-4-methylpentanoic acid
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| Synonyms |
GGTI2418; GGTI 2418; GGTI-2418; PTX 100; PTX-100; PTX100
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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 Vitro) |
DMSO: ~125 mg/mL (~283.1 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2649 mL | 11.3245 mL | 22.6490 mL | |
| 5 mM | 0.4530 mL | 2.2649 mL | 4.5298 mL | |
| 10 mM | 0.2265 mL | 1.1325 mL | 2.2649 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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