cAMP-GEFII Inhibitors
Chemical inhibitors of cAMP-GEFII can affect its function through various mechanisms, primarily by altering the availability of its substrate, cAMP, or by modulating the activity of proteins that are downstream in the signaling pathway. Forskolin is one such inhibitor that directly activates adenylyl cyclase, thereby increasing intracellular cAMP levels. This circumvents the need for cAMP-GEFII activation as the alternative cAMP source fulfills the cellular requirement. Contrarily, both Rp-cAMPS and SQ 22536 take an opposing approach. Rp-cAMPS competes with cAMP, thereby preventing the activation of cAMP-dependent pathways downstream of cAMP-GEFII by obstructing the binding sites for cAMP. SQ 22536, on the other hand, inhibits adenylyl cyclase, curtailing the production of cAMP from ATP, which leads to a subdued activity in the cAMP signaling pathway that involves cAMP-GEFII.
Additionally, several inhibitors target proteins that are downstream of cAMP-GEFII, indirectly diminishing its functional necessity. Myristoylated PKI and H-89 are potent inhibitors of PKA, with Myristoylated PKI being a peptide inhibitor and H-89 a small molecule inhibitor. By blocking PKA activation, they decrease the cellular demand for cAMP, thus indirectly reducing the functional requirement for cAMP-GEFII. KT 5720 also inhibits PKA, echoing the indirect inhibition seen with the previous two chemicals. Adenosine engages by activating adenosine receptors that have an inhibitory effect on adenylyl cyclase, subsequently lowering cAMP levels and indirectly diminishing cAMP-GEFII's activity. MDL-12330A follows a similar path by directly inhibiting adenylyl cyclase. W7 works upstream by antagonizing calmodulin, which can regulate adenylyl cyclase, thereby affecting cAMP concentrations and consequentially cAMP-GEFII activity. Sp-cAMPS, although a cAMP analog, activates PKA directly, making the role of cAMP-GEFII less critical. Lastly, ZM 241385 targets the adenosine A2A receptor. ZM 241385 reduces cAMP production by antagonizing the A2A receptor, thus reducing the functional reliance on cAMP-GEFII.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Forskolin | 66575-29-9 | sc-3562 sc-3562A sc-3562B sc-3562C sc-3562D | 5 mg 50 mg 1 g 2 g 5 g | $78.00 $153.00 $740.00 $1413.00 $2091.00 | 73 | |
Forskolin directly activates adenylyl cyclase, which increases intracellular levels of cAMP, therefore functionally inhibiting cAMP-GEFII by providing an alternative cAMP source that bypasses the need for cAMP-GEFII activation. | ||||||
PKI (14-22) amide (myristoylated) | 201422-03-9 | sc-471154 | 0.5 mg | $135.00 | 2 | |
This peptide inhibitor of protein kinase A (PKA) blocks PKA activation. Since PKA is downstream of cAMP-GEFII in the cAMP signaling pathway, the inhibition of PKA results in reduced demand for cAMP, thus indirectly decreasing the functional requirement for cAMP-GEFII. | ||||||
Rp-cAMPS | 151837-09-1 | sc-24010 | 1 mg | $203.00 | 37 | |
Rp-cAMPS is a competitive inhibitor of cAMP and therefore can inhibit the cAMP-dependent pathways downstream of cAMP-GEFII by blocking cAMP binding sites, leading to decreased activation of these pathways and an indirect functional inhibition of cAMP-GEFII. | ||||||
SQ 22536 | 17318-31-9 | sc-201572 sc-201572A | 5 mg 25 mg | $95.00 $363.00 | 13 | |
SQ 22536 is an adenylyl cyclase inhibitor that reduces the production of cAMP from ATP. With less cAMP available, the signaling pathway that cAMP-GEFII is part of will be less active, leading to an indirect functional inhibition of cAMP-GEFII. | ||||||
KT 5720 | 108068-98-0 | sc-3538 sc-3538A sc-3538B | 50 µg 100 µg 500 µg | $138.00 $220.00 $972.00 | 47 | |
KT 5720 is another inhibitor of PKA. By inhibiting PKA, it indirectly reduces the functional activation of cAMP-mediated signaling pathways, thereby indirectly inhibiting cAMP-GEFII which operates upstream of PKA. | ||||||
Adenosine | 58-61-7 | sc-291838 sc-291838A sc-291838B sc-291838C sc-291838D sc-291838E sc-291838F | 1 g 5 g 100 g 250 g 1 kg 5 kg 10 kg | $34.00 $48.00 $300.00 $572.00 $1040.00 $2601.00 $4682.00 | 1 | |
Adenosine activates adenosine receptors, which can inhibit adenylyl cyclase activity. This results in lower cAMP levels, which in turn would reduce the functional activity of cAMP-GEFII due to decreased cAMP availability in the signaling pathway. | ||||||
ML-9 | 105637-50-1 | sc-200519 sc-200519A sc-200519B sc-200519C | 10 mg 50 mg 100 mg 250 mg | $112.00 $449.00 $673.00 $1224.00 | 2 | |
MDL-12330A is an adenylyl cyclase inhibitor, which would lead to diminished production of cAMP and therefore indirectly inhibit cAMP-dependent pathways including those involving cAMP-GEFII. | ||||||
W-7 | 61714-27-0 | sc-201501 sc-201501A sc-201501B | 50 mg 100 mg 1 g | $166.00 $306.00 $1675.00 | 18 | |
W7 is a calmodulin antagonist. Since calmodulin can be involved in the regulation of adenylyl cyclase which in turn affects cAMP levels, W7 can thereby indirectly inhibit the signaling pathways that cAMP-GEFII is part of. | ||||||
Sp-cAMPS | 93602-66-5 | sc-201571 | 1 mg | $97.00 | 3 | |
Sp-cAMPS is a cAMP analog that activates PKA but is resistant to degradation by phosphodiesterases. By activating PKA directly, it can bypass cAMP-GEFII, leading to its functional inhibition due to reduced necessity for its activity in the signaling pathway. | ||||||
ZM 241385 | 139180-30-6 | sc-361421 sc-361421A | 5 mg 25 mg | $92.00 $356.00 | 1 | |
ZM 241385 is an antagonist of the adenosine A2A receptor. By inhibiting A2A, which normally stimulates adenylyl cyclase, it leads to reduced cAMP production and thus indirectly inhibits cAMP-GEFII by reducing cAMP availability in the pathway. | ||||||