| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
IC50: 21 nM (GGTase I)[1]
GGTI-2154 hydrochloride specifically targets geranylgeranyltransferase I (GGTase I), an enzyme that catalyzes the transfer of a geranylgeranyl isoprenoid group to the C-terminal cysteine residue of proteins containing a CAAX motif (where C is cysteine, A is an aliphatic amino acid, and X is leucine). GGTase I is responsible for the geranylgeranylation of small GTPases such as Rho, Rac, and Rap1. |
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| ln Vitro |
GGTI-2154 has an IC50 of 21 nM and prevents the transfer of geranylgeranyl from [3H]GGPP to H-Ras CVLL[1].
In vitro, GGTI-2154 hydrochloride (0.1-1000 nM) inhibits the transfer of geranylgeranyl from [3H]GGPP to H-Ras CVLL (a CAAX motif substrate), with an IC50 of 21 nM. It inhibits the prenylation of RhoA and Rap1 in cells, leading to disruption of downstream signaling pathways involved in cell proliferation, migration, and survival. It shows selectivity >200-fold over FTase. |
| ln Vivo |
In MMTV-v-Ha-Ras transgenic mice, GGTI-2154 (100 mg/kg/day; sc for 14 days) causes regression of breast tumors[2]. In nude mice, GGTI-2154 (50 mg/kg/day; ip for 50 days) suppresses the formation of A-549 tumors by 60%[1].
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| Enzyme Assay |
For non-cellular GGTase I inhibition, purified recombinant human GGTase I (alpha/beta heterodimer) is incubated with the substrate biotinylated H-Ras CVLL peptide or other CAAX-containing peptide (e.g., K-Ras 4B CVIM) and [3H]GGPP (or unlabeled GGPP for non-radioactive assays) in reaction buffer containing 10-50 uM ZnCl2 and 5-10 mM DTT. Varying concentrations of GGTI-2154 hydrochloride (0.01-10,000 nM) are added. After 30-60 minutes at 37degC, the reaction is quenched. For radioactive assays, the geranylgeranylated product is captured on streptavidin-coated filter plates and counted by scintillation. For non-radioactive assays, product is detected by a homogeneous time-resolved FRET (HTRF) assay using anti-geranylgeranyl antibody.
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| Cell Assay |
For cell-based prenylation inhibition, cancer cell lines (e.g., HeLa, MDA-MB-231, HCT116) are treated with GGTI-2154 hydrochloride (0.1-50 uM) for 24-72 hours. Cell lysates are prepared, and prenylation of Rap1 or RhoA is assessed by Western blotting (non-prenylated Rap1/RhoA migrate faster on SDS-PAGE) or by a prenylation-specific antibody. Cell viability is measured by MTT or CellTiter-Glo.
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| Animal Protocol |
Animal/Disease Models: MMTV-v-Ha-ras transgenic mice bearing mammary carcinoma[2]
Doses: 100 mg/kg/day Route of Administration: Sc with osmotic mini-pumps for 14 days Experimental Results: Halted the tumors aggressive growth. Resulted in rapid tumor regression within 3 days of initiation of drug treatment. For in vivo evaluation, GGTI-2154 hydrochloride is evaluated in mouse xenograft models of cancer. Female athymic nude mice are subcutaneously implanted with cancer cells (e.g., HCT116, MDA-MB-231, or pancreatic cancer cells). When tumors reach 100-200 mm3, GGTI-2154 hydrochloride (5-50 mg/kg) is administered intraperitoneally once daily for 14-28 days. Tumor volume is measured twice weekly. For pharmacodynamic studies, tumor lysates are analyzed for Rap1 or RhoA prenylation by Western blot. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for GGTI-2154 hydrochloride are limited. As a small molecule (MW 456.97, C24H29ClN4O3), it is expected to have moderate oral bioavailability. No detailed PK parameters (Cmax, AUC, t½) are publicly available.
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| Toxicity/Toxicokinetics |
GGI-2154 hydrochloride is well tolerated in animal models at effective doses (10-50 mg/kg, i.p.). Potential on-target toxicities include effects on geranylgeranylated proteins (Rho, Rac, Rap1), which are involved in a wide range of cellular functions. No formal LD50 or MTD values are publicly available.
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| References |
[1]. Sun J, et, al. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res. 1999 Oct 1;59(19):4919-26.
[2]. Sun J, et, al. Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice. Cancer Res. 2003 Dec 15;63(24):8922-9. |
| Additional Infomation |
GGTI-2154 hydrochloride is a research-grade GGTase I inhibitor, not approved for human therapy. It is valuable for studying the role of protein geranylgeranylation in cancer, inflammation, and other diseases. The high selectivity for GGTase I over FTase makes it a useful tool for dissecting the specific contributions of geranylgeranylated vs. farnesylated proteins. No clinical trials are registered for GGTI-2154 hydrochloride.
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| Molecular Formula |
C24H29CLN4O3
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|---|---|
| Molecular Weight |
456.965064764023
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| Exact Mass |
456.192
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| CAS # |
478908-50-8
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| Related CAS # |
GGTI-2154;251577-10-3
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| PubChem CID |
69892739
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
599
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| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC1=CC=CC=C1C2=C(C=CC(=C2)NCC3=CN=CN3)C(=O)N[C@@H](CC(C)C)C(=O)O.Cl
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| InChi Key |
JQRKKNPKMYXQRS-FTBISJDPSA-N
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| InChi Code |
InChI=1S/C24H28N4O3.ClH/c1-15(2)10-22(24(30)31)28-23(29)20-9-8-17(26-13-18-12-25-14-27-18)11-21(20)19-7-5-4-6-16(19)3;/h4-9,11-12,14-15,22,26H,10,13H2,1-3H3,(H,25,27)(H,28,29)(H,30,31);1H/t22-;/m0./s1
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| Chemical Name |
(2S)-2-[[4-(1H-imidazol-5-ylmethylamino)-2-(2-methylphenyl)benzoyl]amino]-4-methylpentanoic acid;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, 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 : 250 mg/mL (547.08 mM)
H2O : 4.76 mg/mL (10.42 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 25 mg/mL (54.71 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 250.0 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: ≥ 25 mg/mL (54.71 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 250.0 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: ≥ 25 mg/mL (54.71 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 | 2.1883 mL | 10.9416 mL | 21.8833 mL | |
| 5 mM | 0.4377 mL | 2.1883 mL | 4.3767 mL | |
| 10 mM | 0.2188 mL | 1.0942 mL | 2.1883 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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