Physicochemical Properties
| Molecular Formula | C23H31N5O4 |
| Molecular Weight | 441.52 |
| Exact Mass | 441.238 |
| Elemental Analysis | C, 62.57; H, 7.08; N, 15.86; O, 14.49 |
| CAS # | 501010-06-6 |
| Related CAS # | 501010-05-5;501010-06-6 (free acid);1044590-78-4 (sodium); |
| PubChem CID | 11539477 |
| Appearance | Solid powder |
| LogP | 2.262 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 32 |
| Complexity | 667 |
| Defined Atom Stereocenter Count | 2 |
| 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 |
| InChi Key | COLCNDRDBCLVOC-ICSRJNTNSA-N |
| 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) |
| Chemical Name | (2S)-2-[[(2S)-2-benzyl-4-[(5-methyl-1H-imidazol-4-yl)methyl]-3-oxopiperazine-1-carbonyl]amino]-4-methylpentanoic acid |
| Synonyms | GGTI2418; GGTI 2418; GGTI-2418; PTX 100; PTX-100; PTX100 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | GGTase I (IC50 = 9.5 nM); FTase (IC50 = 53 μM) |
| 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]. |
| 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]. |
| 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 |
| References |
[1]. Blockade of protein geranylgeranylation inhibits Cdk2-dependent p27Kip1 phosphorylation on Thr187 and accumulates p27Kip1 in the nucleus: implications for breast cancer therapy. Mol Cell Biol. 2009 Apr;29(8):2254-63. [2]. PTEN counteracts FBXL2 to promote IP3R3- and Ca2+-mediated apoptosis limiting tumour growth. Nature. 2017 Jun 22;546(7659):554-558. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~125 mg/mL (~283.1 mM) |
| 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. 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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |