| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
DRI-C21045 targets CD40-CD40L costimulatory protein-protein interaction (PPI) (IC₅₀ = 0.17 μM) [1, 2, 4, 6]
DRI-C21045 inhibits CD40L-induced NF-κB activation (IC₅₀ = 17.1 μM) and CD40L-induced B cell proliferation (IC₅₀ = 4.5 μM) [2, 4, 6] |
|---|---|
| ln Vitro |
CD40L-induced NF-κB activation in CD40 sensor cells is concentration-dependently inhibited by DRI-C21045 (3.2-100 μM; 18 h) [1]. Primary B cells' CD40L-induced functional activation is blocked by DRI-C21045 (0.6–50 μM; 48 hours) [1]. In THP-1 cells, CD40L-induced MHC-II upregulation is inhibited by DRI-C21045 (0.4-50 μM; 48 hours) [1]. The 48-hour DRI-C21045 (2-100 μM) inhibits the proliferation of B cells induced by CD40L [1]. At concentrations of up to 500 µM, DRI-C21045 exhibits no potential genotoxicity and no indications of cytotoxicity [1].
- In cell-free ELISA-type assay, DRI-C21045 concentration-dependently inhibited human CD40-CD40L interaction, with no significant inhibition of human TNF-R1-TNF-α interaction at effective concentrations [1] - In CD40 sensor cells, DRI-C21045 (3.2–100 μM, 18 h) concentration-dependently inhibited CD40L (20 ng/mL)-induced NF-κB activation, with an anti-CD40L antibody as positive control [1, 2] - In primary human B cells stimulated with IL-4 (0.2 μg/mL) and CD40L (0.2 μg/mL), DRI-C21045 (0.6–50 μM, 48 h) blocked CD40L-induced functional activation (AID activation quantified via fluorescent marker by flow cytometry) and (2–100 μM, 48 h) inhibited CD40L-induced B cell proliferation [1, 2] - In THP-1 myeloid cells, DRI-C21045 (0.4–50 μM, 48 h) inhibited CD40L-induced MHC-II upregulation [2] - At concentrations up to 500 μM, DRI-C21045 showed no potential genotoxicity or cytotoxicity [2] |
| ln Vivo |
In a mouse skin allograft model, DRI-C21045 (30 mg/kg; daily, subcutaneous; in 20% HPβCD) prolongs graft life [1]. In draining lymph nodes (DLN), DRI-C21045 (20–60 mg/kg; subcutaneous injection twice daily; dissolved in 20% HPβCD) suppresses T cell growth induced by alloantigen [1].
- In a mouse skin allograft model (full-thickness ear skin transplantation from Balb/c to dorsal thorax of C57BL/6 mice), DRI-C21045 (30 mg/kg, daily subcutaneous injection in 20% HPβCD) combined with CTLA4-Ig (250 μg on days 0, 2, 4, 6) significantly prolonged skin allograft survival compared to CTLA4-Ig alone [1, 2] - In Balb/c mice receiving footpad injection of DBA-2 mouse splenocytes, DRI-C21045 (20–60 mg/kg, twice daily subcutaneous injection in 20% HPβCD from day -1 to 3) dose-dependently suppressed alloantigen-induced T cell expansion in draining popliteal lymph nodes [1, 2] |
| Enzyme Assay |
- Cell-free CD40-CD40L interaction assay: The interaction between human CD40 and CD40L was quantified using an ELISA-type assay. DRI-C21045 at different concentrations was added, and the inhibitory effect was evaluated by measuring normalized percent binding. Data were presented as average ± SD from 3 independent experiments with triplicates per condition, and standard binding curves were fitted [1]
- CD40L-induced NF-κB activation assay in CD40 sensor cells: CD40 sensor cells were treated with DRI-C21045 at various concentrations (3.2–100 μM) for 18 h, then stimulated with CD40L (20 ng/mL). NF-κB activation level was detected, and data were collected from 4 independent experiments with duplicates per condition, normalized to CD40L-activated cells alone [1, 2] |
| Cell Assay |
- Primary human B cell functional activation assay: Human B cells were transfected with a lentiviral construct containing the aicda promoter/enhancer fused to Ds-Red reporter. Transfected cells were treated with DRI-C21045 (0.6–50 μM) and stimulated with IL-4 (0.2 μg/mL) + CD40L (0.2 μg/mL) for 48 h. AID activation was evaluated by Ds-Red level via flow cytometry, with an anti-CD40L antibody (33.3 nM) as positive control [1, 2]
- Primary human B cell proliferation assay: Primary human B cells were treated with DRI-C21045 (2–100 μM) and stimulated with CD40L for 48 h. Cell proliferation was measured to assess inhibitory effect [2] - THP-1 cell MHC-II upregulation assay: THP-1 cells were treated with DRI-C21045 (0.4–50 μM) and stimulated with CD40L for 48 h. MHC-II expression level was detected to evaluate inhibitory activity [2] |
| Animal Protocol |
Animal/Disease Models: Full-thickness ear skin transplantation from BALB/c to dorsal thorax of C57BL/6 [1]
Doses: 30 mg/kg Route of Administration: daily subcutaneous injection; in 20% w/v hydroxypropyl-β-cyclo Administration of dextrin (HPβCD) in solution resulted in prolonged skin allograft survival. - Mouse skin allograft experiment: C57BL/6 mice were transplanted with full-thickness ear skin from Balb/c mice. Mice were treated with DRI-C21045 (30 mg/kg, daily subcutaneous injection) dissolved in 20% w/v hydroxypropyl-β-cyclodextrin (HPβCD), combined with CTLA4-Ig (250 μg administered on days 0, 2, 4, 6). Graft survival time was monitored, with 5–8 mice per group [1, 2] - Mouse draining lymph node (DLN) T cell expansion experiment: Balb/c mice received footpad injection of DBA-2 mouse splenocytes. Mice were treated with DRI-C21045 (20–60 mg/kg, twice daily subcutaneous injection) dissolved in 20% HPβCD from day -1 to 3. On day 3 post-alloantigen challenge, popliteal DLNs were collected and DLN cell count was performed to assess T cell expansion, with 3–4 mice per group [1, 2] - Mouse pharmacokinetic experiment: Mice received a single subcutaneous dose of DRI-C21045 (1.6 mg/mouse). Plasma concentrations of DRI-C21045 were measured at different time points, and data were fitted with a one-compartment pharmacokinetic model with first-order absorption and elimination (n = 4, average ± SD) [1] |
| ADME/Pharmacokinetics |
- In mice, after a single subcutaneous injection of DRI-C21045 (1.6 mg/mouse), the plasma concentration-time curve conformed to a one-compartment model of first-order absorption and first-order elimination [1].
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| Toxicity/Toxicokinetics |
In vitro studies showed that DRI-C21045 at concentrations up to 500 μM did not exhibit cytotoxicity or genotoxicity [2]. In vivo studies showed that mice treated with DRI-C21045 at doses up to 60 mg/kg (twice daily subcutaneous injection) did not show significant toxicity (e.g., weight loss, clinical symptoms) [1, 2].
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| References |
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| Additional Infomation |
- Chemical properties of DRI-C21045: CAS No. 2101765-81-3; Molecular weight 580.61; Molecular formula C₃₂H₂₄N₂O₇S [4, 6]
- Solubility of DRI-C21045: Solubility in DMSO is 2 mg/mL (3.44 mM) (sonication required) [6] - Storage conditions of DRI-C21045: Powder can be stored for 3 years at -20°C; solution can be stored for 2 years at -80°C [6] - DRI-C21045 is a highly effective and selective small molecule inhibitor of CD40-CD40L PPI, which has been developed for immunomodulation in transplantation and autoimmune diseases [1, 2] |
| Molecular Formula |
C32H24N2O7S
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|---|---|
| Molecular Weight |
580.607167243958
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| Exact Mass |
580.13
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| CAS # |
2101765-81-3
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| PubChem CID |
129275747
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| Appearance |
Off-white to gray solid powder
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
42
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| Complexity |
1050
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC=C2C=CC=C(C2=1)NC(C1C=CC(=CC=1)C1C=CC(=CC=1)NC(C1C=CC(C(=O)OC)=CC=1)=O)=O)(=O)(=O)O
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| InChi Key |
BZAWLSZPOBGURT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H24N2O7S/c1-41-32(37)25-14-12-23(13-15-25)30(35)33-26-18-16-21(17-19-26)20-8-10-24(11-9-20)31(36)34-27-6-2-4-22-5-3-7-28(29(22)27)42(38,39)40/h2-19H,1H3,(H,33,35)(H,34,36)(H,38,39,40)
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| Chemical Name |
8-[[4-[4-[(4-methoxycarbonylbenzoyl)amino]phenyl]benzoyl]amino]naphthalene-1-sulfonic acid
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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 : ~2 mg/mL (~3.44 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 0.5 mg/mL (0.86 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 sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 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 | 1.7223 mL | 8.6116 mL | 17.2233 mL | |
| 5 mM | 0.3445 mL | 1.7223 mL | 3.4447 mL | |
| 10 mM | 0.1722 mL | 0.8612 mL | 1.7223 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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