| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
TCR (T‑cell antigen receptor).
|
|---|---|
| ln Vitro |
KRM‑III potently inhibits TCR‑induced NFAT nuclear factor activation and T‑cell proliferation with an IC₅0 of approximately 5 microM. It also blocks PMA (phorbol myristate acetate) and ionomycin‑induced NFAT activation, suggesting its site of action is downstream of TCR signaling but proximal to PKC and calcium flux in the T‑cell activation pathway.
|
| ln Vivo |
KRM‑III is orally active and demonstrates anti‑inflammatory activity in vivo. In preclinical models of T‑cell mediated inflammation, oral administration suppresses T‑cell activation and reduces production of pro‑inflammatory cytokines. Its oral bioavailability makes it suitable for in vivo studies of immune modulation.
|
| Enzyme Assay |
Not available. Generic TCR‑NFAT pathway assay: Jurkat T cells (2×10⁶) are transiently transfected with an NFAT‑luciferase reporter plasmid (0.5 microg) using electroporation. After 24 h, cells are pre‑incubated with KRM‑III (0‑100 microM) for 1 h, then stimulated with anti‑CD3 antibody (1 microg/mL, OKT3 clone) or with PMA (20 ng/mL) plus ionomycin (1 microM) for 6 h. Cells are lysed, and luciferase activity is measured using a luminometer with a reporter lysis buffer and luciferase substrate. IC₅0 is calculated.
|
| Cell Assay |
Human primary T cells are isolated from healthy donor PBMCs using CD3+ magnetic beads and cultured in RPMI‑1640 with 10% FBS and IL‑2 (20 IU/mL). Cells are seeded in 96‑well round‑bottom plates (1×10⁵/well) pre‑coated with anti‑CD3 antibody (1 microg/mL) and anti‑CD28 antibody (0.5 microg/mL). KRM‑III (0‑50 microM) is added at the time of stimulation. After 48‑72 h, T‑cell proliferation is assessed by [3H]‑thymidine incorporation (1 microCi/well for the final 16 h) or by CFSE dilution measured by flow cytometry. Supernatants are collected for IL‑2 and IFN‑gamma ELISA. Cell viability is assessed by Annexin V/PI staining.
|
| Animal Protocol |
KRM‑III is formulated in 0.5% methylcellulose or 10% DMSO/5% Tween‑80/85% saline for oral gavage. For the DTH (delayed‑type hypersensitivity) model: female BALB/c mice are sensitized on day 0 by subcutaneous injection of 100 microL of 0.5% oxazolone in acetone/olive oil (4:1) on the shaved abdomen. On day 6, mice receive oral KRM‑III (10‑100 mg/kg) 1 h before challenge. The right ear is challenged with 20 microL of 0.5% oxazolone, the left ear receives vehicle control. Ear swelling is measured at 24 h using a digital caliper. Ear biopsies are taken for histology (H&E, CD3 immunohistochemistry) and cytokine ELISA (IL‑2, IFN‑gamma).
|
| ADME/Pharmacokinetics |
No PK data reported for KRM‑III. For structurally similar T‑cell inhibitors: oral administration (20‑50 mg/kg) in mice yields Cmax of 0.5‑2 microM at Tmax of 0.5‑2 h. Terminal t1/2 is 2‑4 h. Volume of distribution (Vd) is moderate (1‑2 L/kg). Plasma protein binding is typically >90%. Oral bioavailability is moderate (30‑50%). The compound shows good distribution to lymphoid organs (spleen, lymph nodes, thymus).
|
| Toxicity/Toxicokinetics |
No toxicity data reported. Generic acute toxicity study: ICR mice (20‑25 g, 5 animals/sex/group) receive a single oral gavage of KRM‑III at doses of 100, 300, and 1000 mg/kg in 0.5% methylcellulose. Animals are observed for clinical signs (hunched posture, piloerection, ataxia, tremors, convulsions, changes in respiration, diarrhea) at 0.5, 1, 2, 4, 8, 24, and 48 h, and then daily for 14 days. Body weights are recorded on days 1, 3, 5, 7, 10, and 14. At termination, all animals are necropsied for gross pathological examination of organs.
|
| References | |
| Additional Infomation |
KRM‑III is a research‑only chemical inhibitor of T‑cell activation via the TCR pathway. Its mechanism involves suppression of NFAT nuclear translocation and transcriptional activity. It is not approved for human use and has not been developed clinically. The compound is used as a pharmacological tool to study T‑cell activation, TCR signaling, and the role of T cells in autoimmune and inflammatory diseases. Some studies suggest its potential as a lead compound for developing immunosuppressive therapies.
|
| Molecular Formula |
C15H12N2S
|
|---|---|
| Molecular Weight |
252.33
|
| Exact Mass |
252.072
|
| CAS # |
79220-94-3
|
| PubChem CID |
736689
|
| Appearance |
Off-white to light brown solid powder
|
| LogP |
3.828
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
1
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
18
|
| Complexity |
338
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC=C(C=C1)C2=CN(C(=S)N2)C3=CC=CC=C3
|
| InChi Key |
QKOAQVKXZJFMET-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C15H12N2S/c18-15-16-14(12-7-3-1-4-8-12)11-17(15)13-9-5-2-6-10-13/h1-11H,(H,16,18)
|
| Chemical Name |
3,5-diphenyl-1H-imidazole-2-thione
|
| 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: 100 mg/mL (396.31 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.91 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 (9.91 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9631 mL | 19.8153 mL | 39.6306 mL | |
| 5 mM | 0.7926 mL | 3.9631 mL | 7.9261 mL | |
| 10 mM | 0.3963 mL | 1.9815 mL | 3.9631 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
