splicing

Branaplam (LMI 070) is a highly potent, selective and orally active small molecule SMN2 splicing modulator.

CD33 splicing modulator 1 (Compound 1) is a CD33 splicing modulator that targets the CD33 Siglec 3 myeloid cell surface receptor, known for regulating microglial cell activity, and holds potential for studying neurodegenerative diseases such as Alzheimer's disease.

RNA Splicing Modulator 1 (Compound 233) is a modulator of RNA splicing, exhibiting an AC50 value of less than 100 nM [1].

CD33 Splicing Modulator 1 Hydrochloride (Compound 1) is a myeloid lineage cell surface receptor CD33 Siglec 3 modulator involved in regulating microglia activity. This compound promotes exon 2 skipping in cellular mRNA pools and has research potential in addressing neurodegenerative diseases, including Alzheimer's disease [1].

RNA splicing modulator 2 (compound 256) is an RNA splicing modulator [1].

RNA Splicing Modulator 3 (Compound 236) is an effective RNA splicing modulator, exhibiting an AC50 value of less than 100 nM [1].

Risdiplam (RG7916) is a centrally and peripherally distributed and orally administrable small molecule SMN2 pre-mRNA splicing modifier that increases survival motor neuron (SMN) protein levels.

B I09, an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells., an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells., an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells.

SMN-C3 (MV8T2MCK57) is an orally active modulator of SMN2 splicing, and has the potential to treat spinal muscular atrophy (SMA).

SMN-C2 is a selective regulator of SMN2 gene splicing, a risdiplam analogue, a selective RNA-binding ligand that regulates pre-mRNA splicing and acts by binding to SMN2 pre-mRNA.SMN-C2 has the potential to be used in the study of spinal muscular atrophy (SMA).

CLK1 2-IN-3 (Cpd-3) is a potent and selective CLK1 and CLK2 inhibitor with antiproliferative activity and inhibits the activities of CLK1, CLK2, SRPK1, SRPK2, and SRPK3.CLK1 2-IN-3 induces nuclear speckle enlargement, which induces S6K pre-mRNA-selective splicing and subsequent inhibition of cell growth of multiple cancer cell types. cancer cell types cell growth.

HTT-D3 is an orally active, highly efficient Huntington splicing modulator. It induces HTT mRNA degradation, reduces HTT protein levels, and inhibits P-glycoprotein (P-gp) efflux. This compound can be used in Huntington's disease research.

Pladienolide B is a potent spliceosome inhibitor, a macrolide isolated from Streptomyces obtusususus Mer-12, which targets the SF3B1 subunit of the spliceosome.Pladienolide B exerts its antitumor effects by inhibiting pre-mRNA splicing and inducing necrosis.Pladienolide B possesses antitumor activity and can be used to study leukemia and lymphoid tumors. Pladienolide B has antitumor activity and can be used to study leukemia and lymphoid tumors.

Hinokiflavone, a novel modulator of pre-mRNA splicing activity both in vitro and in cellulo, inhibits the assembly of the spliceosome, particularly blocking the formation of the B complex. Additionally, it acts as a SUMO protease inhibitor by impeding the activity of sentrin-specific protease 1 (SENP1). Hinokiflavone also demonstrates significant cytotoxicity, including the inhibition of MMP-9.

1. ISOGINKGETIN (4',4'''-Dimethylamentoflavone), a compound derived from the leaves of Ginkgo biloba, to up-regulate adiponectin secretion with potency comparable to that of rosiglitazone, a known modulator of adiponectin production. 2. Isoginkgetin has anti-tumor activity, the mechanistic basis is splicing inhibition , thus, pre-mRNA splicing inhibitors may represent a novel avenue for development of new anti-cancer agents.3. Isoginkgetin can inhibit tumor cell invasion by regulating phosphatidylinositol 3-kinase Akt-dependent matrix metalloproteinase-9 expression. 4. Isoginkgetin (0.3mg kg ip for 3d) can reduce the level of O2·- in plasma and erythroeyte and sometimes increase the activity of SOD in anoxic rats, the action being stronger than aspirin.

Thailanstatin C, an antiproliferative agent derived from Burkholderia thailandensis MSMB43, functions as a potent inhibitor of pre-mRNA splicing (IC50 = 6.84 μM).

Branaplam is a highly potent, selective and orally active SMN2 splicing modulator. Branaplam increases the amount of functional SMN protein produced by the SMN2 gene through modifying its splicing.

RG7800 hydrochloride is an orally active modulator of SMN2 splicing.

Ipivivint, a first-in-class, orally active and potent CDC-like kinase (CLK) inhibitor, inhibits CLK1 (IC50=1.4 μM), CLK2 (IC50=0.002 μM) and CLK3 (IC50=0.022 μM). Ipivivint reduces Wnt pathway signaling gene expression through inhibiting CLK activity and serine and arginine rich splicing factor (SRSF) phosphorylation and disrupting spliceosome activity. Ipivivint can be used for the research of cancer[1]. Ipivivint (SW480 cells; 0.01~10 μM; 1 hour) potently inhibits SRSF5/6 phosphorylation[1].Ipivivint (SW480 cells; 0.03 μM~3 μM; 48 hour) induced apoptosis[1]..Ipivivint (HEK-293T cells; 0.03 μM~3 μM; 1 hour) inhibits Wnt/β-catenin signaling induced by Wnt3a[1].Ipivivint (SW480 cells; 0.3~10 μM; 6 hour) increases nuclear speckle enlargement[1].Ipivivint (SW480 cells; 0.3~3μM; 24hours) significantly decreases expression of Wnt target genes (AXIN2, LEF1, MYC, and TCF7) and TCF7L2. SM08502 (SW480 cells; 0.03~3μM; 24hours) inhibits cytoplasmic or nuclear fractions protein expression. Ipivivint (NCI-N87 cells) inhibits proliferation[1].Ipivivint strongly inhibits Wnt pathway signaling activity (EC50 = 0.046 μM) in SW480 colon cancer cells[1]. Ipivivint (25 mg/kg; p.o.) potently inhibits tumor SRSF6 phosphorylation[1]. [1]. Tam BY, et al. The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models. Cancer Lett. 2020;473:186-197.

Homocarbonyltopsentin is a small-molecule TSL2-binding compound, binds to pentaloop conformations of TSL2 and promotes a shift to triloop conformations that display enhanced SMN2 exon 7 (E7) splicing (EC50: 16 μM).

The Survival of Motor Neurons (SMN) protein participates in RNA splicing. Decreases in SMN, typically a consequence of defects in the smn1 gene, result in the death of motor neurons and lead to the neurodegenerative disease, spinal muscular atrophy (SMA). Cuspin-1 is a small molecule upregulator of SMN that has been shown in vitro to increase levels of SMN in SMA patient fibroblasts by 50% at 18 μM. Its mechanism of action is thought to involve increased phosphorylation of ERK to initiate Ras-Raf-MEK signaling, which results in an increased rate of SMN translation.

Votoplam functions as a gene splicing modulator, employed in the inhibition of Huntington's disease [1].

PAIR2 is a potent, selective partial antagonist of IRE1α RNase, effectively occupying the ATP-binding site of IRE1α in cells. This action prevents a potent KIRA from inhibiting XBP1 splicing [1].

Votoplam HCl (PTC-518 HCl) is the hydrochloride form of Votoplam.Votoplam is a systemically acting gene splicing regulator that down-regulates the levels of huntingtin protein, which is primarily used to inhibit Huntington's disease (HD).