| 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 |
Lck (64-509) (IC50 <1 nM); LckCD (IC50 = 2 nM)
The primary target of KIN001-051 is Lymphocyte-specific protein tyrosine kinase (LCK). LCK is a member of the Src family of non-receptor protein tyrosine kinases that plays a critical role in the initial steps of T cell receptor signaling, which triggers cytokine production. KIN001-051 is a potent and selective LCK inhibitor that inhibits Lck (64-509) and LckCD isoforms with IC50s of less than 1 and 2 nM, respectively. It is a cell-permeable and ATP-competitive inhibitor. By inhibiting LCK, the compound can modulate T cell activation and immune responses. |
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| 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].
KIN001-051 inhibits LCK with IC50s of less than 1 nM for Lck (64-509) and 2 nM for LckCD isoforms. It is a potent and selective LCK inhibitor that blocks the activity of Src kinases. The compound's potent inhibition of LCK makes it a valuable tool for studying T cell receptor signaling and immune function. Its selectivity for LCK over other kinases contributes to its specificity and reduced off-target effects. |
| 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].
No specific in vivo activity data is publicly available for KIN001-051. As an LCK inhibitor, it would be expected to modulate T cell activation and immune responses in vivo. The compound's potential applications in autoimmune diseases, transplant rejection, and cancer immunotherapy would require evaluation in appropriate in vivo models. However, specific in vivo studies have not been detailed in the available literature. |
| Enzyme Assay |
No specific non-cell assay protocol is available for KIN001-051. For kinase inhibitors, standard cell-free assays use recombinant LCK enzyme and peptide substrates. The compound is incubated with the enzyme and substrate, and kinase activity is measured by phosphorylation of the substrate using radioactive ATP or fluorescent detection methods. These assays provide quantitative data on the compound's potency (IC50) against LCK. Selectivity profiling against a panel of kinases can be performed to assess the compound's specificity.
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| 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].
No specific cell-based assay protocol is available for KIN001-051. For LCK inhibitors, standard cellular assays use T cells or cell lines expressing LCK. Cells are treated with KIN001-051 in the presence or absence of T cell receptor stimulation. LCK autophosphorylation and downstream signaling (e.g., ZAP-70, ERK) are measured by western blot. T cell activation markers such as CD69, CD25, and cytokine production (IL-2, IFN-γ) are measured by flow cytometry or ELISA. Cell proliferation assays can be performed to assess functional effects. |
| 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].
No specific animal protocol is available for KIN001-051. For studying T cell function in vivo, standard models include T cell-mediated autoimmune disease models (e.g., experimental autoimmune encephalomyelitis, collagen-induced arthritis), transplant rejection models, or tumor immunotherapy models. KIN001-051 is administered (route and dose to be determined) for 2-4 weeks. T cell activation, cytokine production, and disease progression are assessed. However, specific protocols have not been detailed in the available literature. |
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for KIN001-051. The compound has a molecular weight of 370.46 and formula C23H22N4O. The SMILES notation is NC1=C2C(N(C3CCCC3)C=C2C4=CC=C(OC5=CC=CC=C5)C=C4)=NC=N1. It is soluble in DMSO and ethanol but insoluble in water. As a small molecule with moderate lipophilicity, it would be expected to have reasonable cell permeability. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
No detailed toxicology data is publicly available for KIN001-051. As a research compound, standard preclinical toxicology would be required for therapeutic development. The compound's selectivity for LCK may contribute to a manageable safety profile, though potential effects on other Src family kinases or off-target proteins would need to be assessed. The compound is for research use only and not for therapeutic applications.
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| References |
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| Additional Infomation |
RK-24466 belongs to the pyrrolopyrimidine class of compounds, with the structure 7H-pyrrolo[2,3-d]pyrimidine, substituted at positions 4, 5, and 7 by amino, 4-phenoxyphenyl, and cyclopentyl groups, respectively. It is a potent Lck inhibitor, inhibiting both the Lck (64-509) and LckCD isoforms (IC50 values less than 1 nM and 2 nM, respectively). It exhibits anti-aging activity and is also an EC 2.7.10.2 (non-specific protein tyrosine kinase) inhibitor. RK-24466 is a primary amino compound, a pyrrolopyrimidine compound, an aromatic amine compound, an aromatic ether compound, and belongs to the cyclopentane class of compounds.
KIN001-051 is also known as RK-24466, Lck inhibitor, C-8863, and KIN 001-51. It has the molecular formula C23H22N4O and molecular weight 370.46. The SMILES notation is NC1=C2C(N(C3CCCC3)C=C2C4=CC=C(OC5=CC=CC=C5)C=C4)=NC=N1. The chemical name is 7-Cyclopentyl-5-(4-phenoxy)phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine. It is a potent and selective LCK inhibitor that inhibits Lck (64-509) and LckCD isoforms with IC50s of less than 1 and 2 nM, respectively. No clinical trial status has been identified. |
| Molecular Formula |
C23H22N4O
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|---|---|
| Molecular Weight |
370.456
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| Exact Mass |
370.179
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| Elemental Analysis |
C, 74.57; H, 5.99; N, 15.12; O, 4.32
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| CAS # |
213743-31-8
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| Related CAS # |
213743-31-8
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| PubChem CID |
6603792
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
605.1±55.0 °C at 760 mmHg
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| Flash Point |
319.7±31.5 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.696
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| LogP |
5.82
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
497
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| Defined Atom Stereocenter Count |
0
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| SMILES |
NC1=C2C(N(C3CCCC3)C=C2C4=CC=C(OC5=CC=CC=C5)C=C4)=NC=N1
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| InChi Key |
FMETVQKSDIOGPX-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
7-cyclopentyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine
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| Synonyms |
KIN001 051; Lck inhibitor; C-8863; KIN001051; C8863; KIN001-051
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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: 37~45 mg/mL (99.9~121.5 mM)
Ethanol: ~5 mg/mL (~13.5 mM) |
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| 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.
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