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CPSF Inhibitors

Chemical inhibitors of the Cleavage and Polyadenylation Specificity Factor (CPSF) can affect the protein through various mechanisms that impede mRNA processing. Flavopiridol and T-025, for instance, target cyclin-dependent kinases, particularly CDK9, which is integral for RNA polymerase II function. Since CPSF activity is contingent on the transcription elongation facilitated by the phosphorylation of RNA polymerase II's C-terminal domain, these inhibitors effectively attenuate CPSF function by stalling transcription at a stage that precedes the cleavage and polyadenylation of pre-mRNA. Similarly, DRB hampers the transition from transcription initiation to elongation by inhibiting CDK9, thereby indirectly suppressing the activity of CPSF. Other compounds, like Triptolide, Isoginkgetin, Meayamycin, Pladienolide B, and Indisulam, disrupt processes that are upstream or directly related to the actions of CPSF. Triptolide inhibits the TFIIH complex, essential for transcription initiation, which in turn is a prerequisite for CPSF-mediated cleavage and polyadenylation. Isoginkgetin impedes spliceosome assembly, thus indirectly affecting CPSF by preventing proper pre-mRNA splicing, a process that needs to be completed before CPSF can perform its function. Meayamycin and Pladienolide B target the spliceosome more directly, binding components such as the SF3b complex, while Indisulam and Sudemycin D6 disrupt splicing factor proteins or modulate spliceosome function, respectively. These actions collectively result in an indirect inhibition of CPSF, as the protein's activity relies on the availability of properly spliced pre-mRNA substrates. Chemicals like Amiloride, although primarily known for other cellular functions, can have an indirect impact on CPSF activity by altering the cellular milieu and affecting mRNA processing. Lastly, Silvestrol and Homoharringtonine target translation initiation and elongation, respectively, thereby reducing the demand for CPSF activity as fewer mRNAs reach the stage where 3' end processing is required. Through these diverse mechanisms, each chemical contributes to the downregulation of CPSF activity by interfering with different stages of gene expression that precede or are necessary for CPSF-mediated mRNA cleavage and polyadenylation.

Product Name	CAS #	Catalog #	QUANTITY	Price	Citations	RATING
Flavopiridol	146426-40-6	sc-202157 sc-202157A	5 mg 25 mg	$78.00 $259.00	41	(3)
Flavopiridol inhibits the cyclin-dependent kinases (CDKs) which are critical in regulating transcription. CPSF is a cleavage and polyadenylation specificity factor involved in pre-mRNA processing and its function is dependent on transcription. By inhibiting CDK9, Flavopiridol suppresses transcription elongation, which is a prerequisite for CPSF to exert its function on nascent pre-mRNA.
DRB	53-85-0	sc-200581 sc-200581A sc-200581B sc-200581C	10 mg 50 mg 100 mg 250 mg	$43.00 $189.00 $316.00 $663.00	6	(1)
DRB acts as an inhibitor of CDK9, a kinase necessary for phosphorylation of the C-terminal domain (CTD) of RNA polymerase II. This phosphorylation is essential for the transition from transcription initiation to elongation, which is a step required for CPSF to carry out its role in mRNA processing.
Triptolide	38748-32-2	sc-200122 sc-200122A	1 mg 5 mg	$90.00 $204.00	13	(1)
Triptolide is a diterpene triepoxide that has been shown to inhibit the activity of XPB, a subunit of the transcription factor TFIIH. By inhibiting TFIIH, it impairs transcription initiation and elongation processes where CPSF performs its cleavage and polyadenylation function.
Isoginkgetin	548-19-6	sc-507430	5 mg	$225.00		(0)
Isoginkgetin is a biflavonoid that inhibits the splicing of pre-mRNA by suppressing the spliceosome assembly. Since CPSF is involved in the cleavage of pre-mRNA during its processing, the inhibition of splicing by Isoginkgetin indirectly inhibits CPSF by blocking the maturation of its pre-mRNA substrates.
Pladienolide B	445493-23-2	sc-391691 sc-391691B sc-391691A sc-391691C sc-391691D sc-391691E	0.5 mg 10 mg 20 mg 50 mg 100 mg 5 mg	$299.00 $5699.00 $11099.00 $25500.00 $66300.00 $2875.00	63	(2)
Pladienolide B targets the spliceosome, binding to the SF3b complex and inhibiting its function. The pre-mRNA processing involving CPSF is contingent on the proper splicing of pre-mRNA; thus, Pladienolide B indirectly inhibits CPSF activity by disrupting the spliceosome, which is upstream of CPSF function.
Amiloride	2609-46-3	sc-337527	1 g	$296.00	7	(1)
Amiloride, primarily known as a diuretic, also inhibits the urokinase-type plasminogen activator receptor (uPAR). uPAR has been implicated in the regulation of mRNA processes, and its inhibition could indirectly inhibit CPSF by altering the cellular environment in which CPSF operates.
Silvestrol	697235-38-4	sc-507504	1 mg	$920.00		(0)
Silvestrol, a compound derived from the plant Aglaia foveolata, inhibits eukaryotic initiation factor 4A (eIF4A) which is essential for the initiation of translation. CPSF is directly involved in mRNA 3' end processing, and by inhibiting translation initiation, Silvestrol indirectly inhibits CPSF by reducing the pool of mRNA available for processing.
Homoharringtonine	26833-87-4	sc-202652 sc-202652A sc-202652B	1 mg 5 mg 10 mg	$52.00 $125.00 $182.00	11	(1)
Homoharringtonine inhibits protein synthesis by preventing the initial elongation step of translation. Since CPSF is required for mRNA processing which is upstream of translation, inhibition of protein synthesis indirectly reduces the functional demand for CPSF activity.

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