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| Targets |
TC-S 7003 targets lymphocyte-specific kinase (Lck), a member of the Src family of tyrosine kinases that plays a critical role in T cell receptor signaling. It inhibits Lck with an IC50 of 7 nM. It also inhibits Lyn (IC50 = 2.1 nM), Src (IC50 = 4.2 nM), and Syk (IC50 = 200 nM) kinases. By inhibiting these kinases, TC-S 7003 modulates immune cell activation and inflammatory responses.
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| ln Vitro |
Lck Inhibitor (compound 25) inhibits the T cell current sensor IL-2 death test (T-cell current, IC50 = 0.53 μM) in the same human T cells and exhibits good efficacy in the T cell current sensor IL-2 death assay (IL-2, IC50 = 0.46 μM). Comparing Lck Inhibitor to other in vitro cell assays employing blocked human cells, the inhibitory effect on the human mixed solution reaction (huMLR) is improved by a factor of ten. Lck Inhibitor also prevents biochemical cell tests and human cell mixed reaction assays from phosphorylating the TCR chain in a Lck-dependent manner. When IL-2 was stimulated using lysate and a calcium ionophore (PMA/iono) in a non-dependent manner, the efficacy of Lck Inhibitor was reduced tenfold. When the human T cell line Jurkat (JKT) was used in a general proliferation assay, Lck Inhibitor showed comparable levels of activity [1].
In vitro, TC-S 7003 is a potent inhibitor of Lck, Lyn, Src, and Syk kinases with IC50 values of 7, 2.1, 4.2, and 200 nM, respectively. It inhibits T cell proliferation. The compound's ability to inhibit multiple kinases involved in immune signaling contributes to its anti-inflammatory activity. Specific details on assay conditions and cell lines used are not extensively provided in the available literature. |
| ln Vivo |
From day 9 to day 17, lick mold (0–60 mg/kg; sidewall once daily) exhibits dose-dependent suppression of arthritis [1]. Following treatment with Lck mold (sidewall 5 mg/kg), the Cmax, AUC0-∞, tmax, and F% were, in that order, 82 ng/mL, 862 ng h/mL, and 17% [1].
TC-S 7003 has anti-inflammatory activity in vivo. As an orally bioactive Lck inhibitor, it can modulate T cell-mediated immune responses. It has been studied for its potential in treating arthritis. The compound's ability to inhibit Lck and other kinases involved in immune signaling makes it a promising candidate for autoimmune and inflammatory diseases. Specific in vivo efficacy data, including dosing regimens and animal models, are not extensively provided. |
| Enzyme Assay |
In vitro kinase assays for TC-S 7003 involve measuring Lck, Lyn, Src, and Syk kinase activities. Recombinant kinases are incubated with peptide substrates and ATP in the presence of varying concentrations of TC-S 7003. Kinase activity is quantified by measuring phosphorylation of the substrate using radiolabeled ATP or by using antibody-based detection. IC50 values are calculated from concentration-response curves.
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| Cell Assay |
For in vitro cell-based assays, T cells are cultured and stimulated with T cell receptor agonists in the presence of TC-S 7003 at various concentrations. T cell proliferation is assessed by measuring [³H]thymidine incorporation or by using CFSE dilution. Cytokine production (e.g., IL-2, IFN-γ) is measured by ELISA. Cell viability is assessed using MTT or similar assays.
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| Animal Protocol |
Animal/Disease Models: Male Lewis rat (adjuvant-induced arthritis model) [1]
Doses: 0, 30 and 60 mg/kg Route of Administration: Po; one time/day; from day 9 to today 17 Experimental Results: demonstrated protection against arthritis Dose-dependent inhibition, with an estimated ED50 of 24 mg/kg. Animal/Disease Models: SD (SD (Sprague-Dawley)) rat[1] Doses: Po (pharmacokinetic/PK/PK analysis) Route of Administration: 5 mg/kg Experimental Results: Cmax, AUC0-∞, tmax and F% were 82 ng/mL, 862 ng h respectively /mL and 17%, respectively. In vivo animal studies for TC-S 7003 typically use rodent models of arthritis or other inflammatory diseases. The compound is administered orally at doses determined from pharmacokinetic studies. Clinical scores (paw swelling, joint inflammation) are recorded. Inflammatory markers (cytokines, immune cell infiltration) are measured in plasma or tissue homogenates. Histological examination of affected tissues assesses the extent of inflammation and tissue damage. |
| ADME/Pharmacokinetics |
TC-S 7003 has a molecular formula of C31H30N8O and a molecular weight of 530.62. It is an orally bioactive small molecule inhibitor. Detailed pharmacokinetic parameters (absorption, distribution, metabolism, excretion, half-life, bioavailability) are not extensively characterized in the available literature. The compound is for research use only.
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| Toxicity/Toxicokinetics |
Specific toxicity data for TC-S 7003 are not extensively provided in the available literature. As a kinase inhibitor, it would be expected to have a safety profile related to modulation of immune signaling. The compound is for research use only and is not for human or clinical use. Standard toxicology assessments would be required for therapeutic development.
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| References |
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| Additional Infomation |
TC-S 7003 is a potent, orally bioactive, and selective lymphocyte-specific kinase (Lck) inhibitor. It inhibits Lck, Lyn, Src, and Syk kinases with IC50 values of 7, 2.1, 4.2, and 200 nM, respectively. It has anti-inflammatory activity and inhibits T cell proliferation. The compound has been studied for its potential in treating arthritis and other inflammatory diseases. No approved therapeutic status is reported.
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| Molecular Formula |
C31H30N8O
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| Molecular Weight |
530.63
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| Exact Mass |
530.254
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| CAS # |
847950-09-8
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| Related CAS # |
Lck inhibitor 2;944795-06-6
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| PubChem CID |
11785878
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.769
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
40
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| Complexity |
879
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C(=CC=C1)C)N2C(=O)C3=CN=C(N=C3N4C2=NC5=CC=CC=C54)NC6=CC=C(C=C6)N7CCN(CC7)C
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| InChi Key |
BHJJWVDKNXABFS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H30N8O/c1-20-7-6-8-21(2)27(20)39-29(40)24-19-32-30(35-28(24)38-26-10-5-4-9-25(26)34-31(38)39)33-22-11-13-23(14-12-22)37-17-15-36(3)16-18-37/h4-14,19H,15-18H2,1-3H3,(H,32,33,35)
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| Chemical Name |
9-(2,6-dimethylphenyl)-4-[4-(4-methylpiperazin-1-yl)anilino]-1,3,5,9,11-pentazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,10,12,14,16-heptaen-8-one
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| Synonyms |
TCS 7003; TC S 7003; TC-S 7003
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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 : ~100 mg/mL (~188.46 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 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 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 (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 25.0 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 | 1.8846 mL | 9.4228 mL | 18.8455 mL | |
| 5 mM | 0.3769 mL | 1.8846 mL | 3.7691 mL | |
| 10 mM | 0.1885 mL | 0.9423 mL | 1.8846 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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