CD40L Inhibitors
Chemical inhibitors of CD40 ligand (CD40L) employ various molecular mechanisms to impede the signaling pathways crucial for the expression and function of this protein. Cyclosporin A and FK506 (Tacrolimus) directly inhibit the phosphatase calcineurin after binding to their respective immunophilins, cyclophilin and FKBP12. This inhibition prevents the dephosphorylation and subsequent nuclear translocation of the nuclear factor of activated T-cells (NF-AT), a transcription factor essential for initiating CD40L transcription. Ascomycin, sharing structural similarities with FK506, also binds to FKBP12 to exert its inhibitory action on calcineurin, thereby leading to a similar blockade of NF-AT and downregulation of CD40L expression.
Concurrently, Rapamycin, while also forming a complex with FKBP12, diverges in its mode of action by specifically targeting the mammalian target of rapamycin (mTOR) pathway, a different regulatory axis of T cell activation. This results in the suppression of CD40L expression by inhibiting a pathway parallel to those targeted by calcineurin inhibitors. Other chemical inhibitors, such as PD98059, SP600125, and SB203580, target various mitogen-activated protein kinases (MAPKs) like MEK, JNK, and p38 MAPK, respectively. These kinases are part of intricate signaling cascades that, when inhibited, reduce the activation of transcription factors responsible for the upregulation of CD40L. Wortmannin and LY294002 are phosphoinositide 3-kinase (PI3K) inhibitors, which function by obstructing the PI3K/Akt pathway, thereby attenuating the cellular signals required for CD40L expression. Curcumin and Resveratrol, on the other hand, act upstream by inhibiting the activation of NF-κB, another transcription factor involved in the regulation of CD40L. Collectively, these chemical inhibitors converge on critical nodal points within the cellular signaling networks to effectively reduce the functional presence of CD40L without influencing its genetic transcription mechanisms.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Cyclosporin A | 59865-13-3 | sc-3503 sc-3503-CW sc-3503A sc-3503B sc-3503C sc-3503D | 100 mg 100 mg 500 mg 10 g 25 g 100 g | $62.00 $90.00 $299.00 $475.00 $1015.00 $2099.00 | 69 | |
Cyclosporin A inhibits calcineurin after binding to the cytosolic protein cyclophilin of T-lymphocytes. This inhibition specifically and effectively blocks the translocation of NF-AT to the nucleus, which is necessary for the activation of CD40L transcription in T cells. Thus, by preventing NF-AT from initiating CD40L transcription, Cyclosporin A functionally inhibits CD40L. | ||||||
FK-506 | 104987-11-3 | sc-24649 sc-24649A | 5 mg 10 mg | $76.00 $148.00 | 9 | |
FK506 binds to FKBP12, creating a complex that inhibits calcineurin, thereby inhibiting the activation of NF-AT. Without NF-AT, the transcription of CD40L is reduced. As transcription is a prerequisite for the function of proteins, the inhibition of this process by FK506 leads to a functional inhibition of CD40L. | ||||||
Rapamycin | 53123-88-9 | sc-3504 sc-3504A sc-3504B | 1 mg 5 mg 25 mg | $62.00 $155.00 $320.00 | 233 | |
Rapamycin forms a complex with FKBP12, similar to FK506, but instead of targeting calcineurin, it inhibits mTOR. mTOR inhibition affects T cell activation and can downregulate the expression of activation-induced genes, including CD40L. By impeding the signaling pathway necessary for T cell activation, Rapamycin functionally inhibits CD40L. | ||||||
Ascomycin | 104987-12-4 | sc-207303B sc-207303 sc-207303A | 1 mg 5 mg 25 mg | $36.00 $173.00 $316.00 | ||
Ascomycin binds to FKBP12 and inhibits calcineurin, similar to FK506 and Cyclosporin A. This prevents the activation of NF-AT and subsequent CD40L expression in T cells. By inhibiting this pathway, Ascomycin functionally inhibits CD40L. | ||||||
Curcumin | 458-37-7 | sc-200509 sc-200509A sc-200509B sc-200509C sc-200509D sc-200509F sc-200509E | 1 g 5 g 25 g 100 g 250 g 1 kg 2.5 kg | $36.00 $68.00 $107.00 $214.00 $234.00 $862.00 $1968.00 | 47 | |
Curcumin has been shown to inhibit the transcription factor NF-κB, which is involved in the expression of CD40L. By preventing NF-κB activation, curcumin can diminish the transcription of CD40L, which translates to its functional inhibition. | ||||||
Resveratrol | 501-36-0 | sc-200808 sc-200808A sc-200808B | 100 mg 500 mg 5 g | $60.00 $185.00 $365.00 | 64 | |
Resveratrol inhibits the activation of NF-κB, a transcription factor that regulates the expression of many immune response genes, including CD40L. By preventing the activation of NF-κB, resveratrol functionally inhibits the expression and thus the activity of CD40L. | ||||||
PD 98059 | 167869-21-8 | sc-3532 sc-3532A | 1 mg 5 mg | $39.00 $90.00 | 212 | |
PD98059 is an inhibitor of MEK, which is involved in the MAPK/ERK pathway. This pathway can be involved in the activation of transcription factors that regulate CD40L expression. By inhibiting MEK, PD98059 can suppress the signaling required for CD40L expression, thereby functionally inhibiting CD40L. | ||||||
SP600125 | 129-56-6 | sc-200635 sc-200635A | 10 mg 50 mg | $40.00 $150.00 | 257 | |
SP600125 is an inhibitor of JNK, which is part of the MAPK pathway and can influence the activity of transcription factors that regulate CD40L expression. Inhibition of JNK by SP600125 can thus impede the signaling required for CD40L expression and functionally inhibit CD40L. | ||||||
SB 203580 | 152121-47-6 | sc-3533 sc-3533A | 1 mg 5 mg | $88.00 $342.00 | 284 | |
SB203580 is an inhibitor of p38 MAPK. The p38 MAPK pathway is involved in the production of pro-inflammatory cytokines and the expression of molecules like CD40L. By selectively inhibiting p38 MAPK, SB203580 can disrupt the signaling required for CD40L expression, thereby functionally inhibiting CD40L. | ||||||
Wortmannin | 19545-26-7 | sc-3505 sc-3505A sc-3505B | 1 mg 5 mg 20 mg | $66.00 $219.00 $417.00 | 97 | |
Wortmannin is a potent inhibitor of PI3K. PI3K/Akt pathway plays a role in T cell activation and the subsequent expression of CD40L. Inhibition of PI3K by wortmannin can, therefore, functionally inhibit CD40L by hindering the signaling pathways necessary for its expression and activity. | ||||||