| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
|
KIN001-051 (Lck inhibitor; C-8863; KIN-001-051) is a novel, potent, cell-permeable and ATP-competitive inhibitor of Lymphocyte-specific protein tyrosine kinase (LCK, IC50s）.
| Targets |
Lck (64-509) (IC50 <1 nM); LckCD (IC50 = 2 nM)
|
|---|---|
| ln Vitro |
Among a variety of tyrosine, non-receptor tyrosine inhibitors, and tyrosine/threonine inhibitors, RK-24466 is selective for Lck. RK-24466 is at least 100 times more effective than PP1 as a powerful drug against CD3-stimulated IL2 generation in Jurkat cells. Good cell selectivity is demonstrated by RK-24466 [1]. RK-24466 dramatically reduces the proliferation of VSMC. RK-24466 significantly reduces the expression of cell nuclear factor (PCNA) and cyclin D1, promotes phosphorylation of blast tumor protein (pRb), and modifies extracellular signal-regulated mitochondria (ERK) inhibitors to inhibit the proliferation and migration of VSMC[2].
|
| ln Vivo |
In mice models, RK-24466 was administered intraperitoneally at a low dose, with the goal of post-forceps suppression of T cell injection-stimulated (a-CD3 mAb) IL-2 production (ED50=4 mg/kg). (ED50=25 mg/kg), most likely due to the latter regimen's detrimental malabsorption. Additionally, RK-24466 has the ability to suppress probing T cell immunological responses. A 70% suppression of in vitro IFNγ production was noted after the previous agonistic (KLH) challenge of the drained response following three days of treatment of RK-24466 twice daily (100 mg/kg route) during the in vivo priming phase [3]. Following balloon damage to the carotid artery, RK-24466 inhibits VSMC migration from endothelium-depleted aortic rings and neointima [2].
|
| Cell Assay |
CCK-8 is used to measure cellular proliferation after VSMCs are cultured in 10% FBS-supplemented DMEM containing either vehicle (DMSO 2%, v/v) or increasing concentrations of the RK-24466 (1 to 10 μM) for 24 hours in order to investigate the concentration-dependent effect of the RK-24466[2].
|
| Animal Protocol |
Rats: In the group receiving treatment with RK-24466, an intravenous injection of 5 μM of RK-24466 is administered via the femoral vein. The rats are put under anesthesia and have their carotid arteries removed at 14 days following BI. The right carotid artery is injured by balloon along its whole length. An intact intra-animal control is provided by the left carotid artery. The intima to media thickness ratio is measured and an H&E stained section is imaged in order to evaluate the formation of neointima[2].
|
| References |
[1]. Arnold LD, et al. Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I. Bioorg Med Chem Lett. 2000 Oct 2;10(19):2167-70.
[2]. Seo HH, et al. 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d] pyrimidin-4-ylamine inhibits the proliferation and migration of vascular smooth muscle cells by suppressing ERK and Akt pathways. Eur J Pharmacol. 2017 Mar 5;798:35-42. [3]. Burchat AF, et al. Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitorsof lck II. Bioorg Med Chem Lett. 2000 Oct 2;10(19):2171-4 |
| Molecular Formula |
C23H22N4O
|
|---|---|
| Molecular Weight |
370.456
|
| Exact Mass |
370.1794
|
| Elemental Analysis |
C, 74.57; H, 5.99; N, 15.12; O, 4.32
|
| CAS # |
213743-31-8
|
| Related CAS # |
213743-31-8
|
| Appearance |
Solid powder
|
| SMILES |
C1CCC(C1)N2C=C(C3=C(N=CN=C32)N)C4=CC=C(C=C4)OC5=CC=CC=C5
|
| InChi Key |
FMETVQKSDIOGPX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H22N4O/c24-22-21-20(14-27(17-6-4-5-7-17)23(21)26-15-25-22)16-10-12-19(13-11-16)28-18-8-2-1-3-9-18/h1-3,8-15,17H,4-7H2,(H2,24,25,26)
|
| Chemical Name |
7-cyclopentyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine
|
| Synonyms |
KIN001 051; Lck inhibitor; C-8863; KIN001051; C8863; KIN001-051
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 37~45 mg/mL (99.9~121.5 mM)
Ethanol: ~5 mg/mL (~13.5 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (6.07 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 22.5 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: 2.25 mg/mL (6.07 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 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: ≥ 2.25 mg/mL (6.07 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 | 2.6993 mL | 13.4967 mL | 26.9935 mL | |
| 5 mM | 0.5399 mL | 2.6993 mL | 5.3987 mL | |
| 10 mM | 0.2699 mL | 1.3497 mL | 2.6993 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
