| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: =100%
| Targets |
G-5555 targets group I p21-activated kinases (PAKs), specifically PAK1, PAK2, and PAK3. PAKs are serine/threonine kinases that are downstream effectors of the small GTPases Rac and Cdc42. They play important roles in cell proliferation, migration, and survival. By inhibiting PAK1 with a Ki of 3.7 nM, G-5555 blocks signaling pathways involved in cancer cell proliferation and migration. Its high selectivity makes it a valuable tool for studying PAK biology.
|
|---|---|
| ln Vitro |
G-5555 has a Ki of 3.7 nM, making it a strong PAK1 conjugate. Of the 235 interactions evaluated, G-5555 shown good interactions, modifying but inhibiting 8 of them by more than 70%: PAK2, PAK3, KHS1, Lck, MST3, MST4, SIK2, and YSK1. G-5555 has an IC50 of 9, 11, 10, 20, 34, 43, and 52 nM against SIK2, PAK2, KHS1, MST4, YSK1, MST3, and Lck, in that order. G-5555 generally shows good selectivity for group I PAKs. G-5555 exhibits very little action on hERG channels in patch-clamp studies, with an IC50 greater than 10 μM [1]. G-5555 inhibits PAK2 potently, having a Ki of 11 nM. G-5555 had much more growth inhibitory action in the PAK cell line than in non-amplified cell lines in a panel of 23 tumor cell lines [2].
In vitro, G-5555 is a potent inhibitor of group I PAKs, with a Ki of 3.7 nM for PAK1 and 11 nM for PAK2. It shows excellent kinase selectivity, inhibiting only 8 out of 235 kinases tested with >70% inhibition: PAK2, PAK3, KHS1, Lck, MST3, MST4, SIK2, and YSK1. Its effects on cell proliferation and signaling have been characterized in various cell lines. The compound's potency and selectivity make it a valuable tool for studying PAK signaling. |
| ln Vivo |
G-5555 has a deadly half-life and poor blood clearance. High oral bioavailability (F=80%) and good oral exposure (AUC=30 μM h) were attained [1]. G-5555 inhibited phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298 in a simulator H292 non-small cell lung cancer (NSCLC) xenograft study. When given at a final dose of 25 mg hour/kg bid, this model and the PAK1 breast cancer xenograft model MDAMB-175 showed 60% tumor growth inhibition [2].
In vivo, G-5555 has low blood clearance and an acceptable half-life. It has good oral exposure (AUC=30 μM/h) and high oral bioavailability (F=80%). The compound has been studied in mouse H292 non-small cell lung cancer (NSCLC) xenograft models. Its favorable pharmacokinetic properties support its use in in vivo studies. The compound has potential applications in cancer research. |
| Enzyme Assay |
In vitro enzyme assays for G-5555 involve measuring the inhibition of PAK1, PAK2, and PAK3 kinase activity using purified enzyme preparations. The compound is incubated with the kinase and a peptide substrate in the presence of ATP, and phosphorylation is measured using radiometric or fluorescence-based detection methods. The Ki values are determined from kinetic studies. Selectivity is assessed using broad kinase screening panels.
|
| Cell Assay |
In vitro cell-based assays for G-5555 involve treating cancer cell lines with the compound to assess its effects on cell proliferation, migration, and PAK signaling. Cell proliferation is measured using MTT or similar assays. PAK signaling is assessed by measuring the phosphorylation of PAK substrates. Cell migration is assessed using Transwell or wound healing assays. These assays characterize the compound's cellular activity.
|
| Animal Protocol |
In vivo animal experiments for G-5555 have been conducted in mouse H292 non-small cell lung cancer xenograft models. Tumor-bearing mice are treated with G-5555, and tumor growth inhibition is monitored. Pharmacokinetic studies are performed to assess oral exposure and bioavailability. Efficacy endpoints include tumor volume reduction and biomarker analysis. These studies support the compound's potential as an anticancer agent.
|
| ADME/Pharmacokinetics |
G-5555 has a molecular weight of 492.96 and a molecular formula of C25H25ClN6O3. It is a high-affinity group I PAK inhibitor. The compound is soluble in DMSO at 25 mg/mL. It is a white solid with a purity of >98%. It is typically stored at 2-8°C in dry, sealed conditions. Its high oral bioavailability (F=80%) supports its use in in vivo studies.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for G-5555 is not extensively reported. As a PAK inhibitor, its safety profile is related to its effects on PAK signaling in normal tissues. The compound is generally well-tolerated in preclinical studies at therapeutic doses. Comprehensive toxicological studies would be required for therapeutic development. Standard safety precautions should be taken when handling the compound.
|
| References |
|
| Additional Infomation |
G-5555 is a high-affinity group I PAK inhibitor with Ki values of 3.7 nM for PAK1 and 11 nM for PAK2. It shows excellent kinase selectivity. The compound has high oral bioavailability (F=80%). G-5555 has been studied in NSCLC xenograft models. It is a research tool for studying PAK signaling in cancer.
|
| Molecular Formula |
C25H26CL2N6O3
|
|---|---|
| Molecular Weight |
529.4183
|
| Exact Mass |
492.167
|
| CAS # |
1648863-90-4
|
| Related CAS # |
G-5555 hydrochloride
|
| PubChem CID |
91664373
|
| Appearance |
White to light yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
684.6±65.0 °C at 760 mmHg
|
| Flash Point |
367.8±34.3 °C
|
| Vapour Pressure |
0.0±2.1 mmHg at 25°C
|
| Index of Refraction |
1.652
|
| LogP |
1.98
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
35
|
| Complexity |
778
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=NC(=CC=C1)C2=CC(=C(C=C2)C3=CC4=CN=C(N=C4N(C3=O)CC5OCC(CO5)N)NC)Cl
|
| InChi Key |
ZBCMHWUFWQFPLV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H25ClN6O3/c1-14-4-3-5-21(30-14)15-6-7-18(20(26)9-15)19-8-16-10-29-25(28-2)31-23(16)32(24(19)33)11-22-34-12-17(27)13-35-22/h3-10,17,22H,11-13,27H2,1-2H3,(H,28,29,31)
|
| Chemical Name |
8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methylpyridin-2-yl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one
|
| 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 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)
|
| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~50.71 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.07 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 25.0 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: ≥ 2.5 mg/mL (5.07 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 25.0 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: ≥ 2.5 mg/mL (5.07 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 | 1.8889 mL | 9.4443 mL | 18.8886 mL | |
| 5 mM | 0.3778 mL | 1.8889 mL | 3.7777 mL | |
| 10 mM | 0.1889 mL | 0.9444 mL | 1.8889 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA