splice

Telaglenastat (CB 839) (IC50 of 24 nM), an effective, specific, and oral inhibitor, which is bioavailable glutaminase, for recombinant human GAC.

Spliceostatin A is an anticancer agent and splicing inhibitor that inhibits the splicing mechanism of the spliceosome and inhibits mitotic clonal expansion and adipogenesis.Spliceostatin A induces cell cycle arrest in the G1 and G2 M phases, and induces apoptosis.

Spliceostatin A (GMP) refers to the GMP grade reagents of Spliceostatin A. Spliceostatin A is an anticancer agent and splicing inhibitor that inhibits the splicing mechanism of the spliceosome and inhibits mitotic clonal expansion and adipogenesis.Spliceostatin A induces cell cycle arrest in the G1 and G2 M phases, and induces apoptosis.

2-Nitrobenzoic acid (o-Nitrobenzoic acid) is a antiproliferation agent. 2-Nitrobenzoic acid shows IC50 of 8.3 μM to jurkat cell line expressing T type calcium channel alpha 1H or its splice variant delta 25.

Ailanthone (AIL) is a natural compound derived from the tree Ailanthus altissima and has anti-hepatocellular carcinoma (HCC) properties. It can induce G0 G1 phase cell cycle arrest by downregulating the expression of cyclins and CDKs, while upregulating the expression of p21 and p27. Additionally, Ailanthone is a potent androgen receptor (AR) inhibitor, capable of inhibiting both the full-length androgen receptor (IC50: 69 nM) and constitutively active splice variants (IC50: 309 nM).

(E Z)-TG003 is a potent and ATP-competitive inhibitor of Cdc2-like kinase (Clk).

CFT1946 is a Bifunctional Degradation Activating Compound (BiDAC) degrader that contains a ligand targeting the BRAF kinase domain linked to a cereblon ligand. CFT1946 is able to degrade BRAF V600E (class I), G469A (class II), G466V (class III) mutations and p61-BRAFV600E splice variants while maintaining excellent selectivity for the proteome including WT BRAF and CRAF.

NSC 194308, an enhancer of U2AF2-RNA complexes, promotes the association of the U2AF1-U2AF2-SF1-splice site RNA complex by targeting a site between U2AF2 RNA recognition motifs (RRM1 and RRM2). It inhibits pre-mRNA splicing by stalling spliceosome assembly at the stage where U2AF recruits U2 snRNP to the branchpoint. Additionally, NSC 194308 strengthens the binding of pre-mRNA to U2AF2, selectively inducing cell death in leukemia cell lines with spliceosome mutations [1].

Telaglenastat (CB-839) hydrochloride is a first-in-class, reversible, and orally active inhibitor of glutaminase 1 (GLS1), selectively inhibiting the splice variants KGA (kidney-type glutaminase) and GAC (glutaminase C), as opposed to GLS2. Telaglenastat hydrochloride has an IC50 of 23 nM for endogenous glutaminase in mouse kidney and 28 nM in the brain, inducing autophagy and exhibiting antitumor activity.

Minnelide is an effective therapy against pancreatic cancer. Minnelide Inhibits Androgen Dependent, Castration Resistant Prostate Cancer Growth by Decreasing Expression of Androgen Receptor Full Length and Splice Variants. Minnelide reduced tumor volume in multiple models of pancreatic cancer. Minnelide was a more effective drug against pancreatic cancer models. It effectively reduced tumor burden and tumor related morbidity in different unique but complementary mouse models. It reduced metastatic spread and increased survival in the different models as well.

EPI-7170 is a ralaniten analogue and a potent antagonist of the androgen receptor N-terminal structural domain, blocking the transcriptional activity of the full-length AR (FL-AR) and AR splice variants (AR-Vs). EPI-7170 exhibits antitumor activity against enzalutamide resistant debulking resistant prostate cancer (CRPC).

AAK1-IN-1 (example 123) is an AAK1 (adaptor associated kinase 1) inhibitor with an IC50 of 2.2 nM. AAK1-IN-1 can be used for neurodegenerative diseases research[1]. Adaptor associated kinase 1 (AAK1) is a member of the Arkl Prkl family of serine threonine kinases. AAKl mRNA exists in two splice forms termed short and long. The long form predominates and is highly expressed in brain and heart. AAKl is enriched in synaptosomal preparations and is co-localized with endocytic structures in cultured cells. AAKl modulates clatherin coated endocytosis, a process that is important in synaptic vesicle recycling and receptor-mediated endocytosis[1]. [1]. Guanglin Luo, et al. Biaryl kinase inhibitors. WO2015153720A1.

Ar-V7-IN-1 is a highly potent inhibitor specifically targeting Ar-V7, a splice variant of the androgen receptor exhibiting hormone-independent behavior, and shows promise for researching various indications, notably cancers such as prostate cancer[1].

1-Naphthyl phosphate potassium salt inhibits non-specific phosphatase.

BWA-522 is a small molecule, orally available protein-targeting chimera (PROTAC) that potentates the degradation of both full-length androgen receptor (AR-FL) and the AR-V7 splice variant. It specifically antagonizes the N-terminal domain (AR-NTD) of the androgen receptor (Androgen Receptor), prompting apoptosis in prostate cancer (PC) cells. In LNCaP xenograft models, BWA-522 demonstrated tumor growth inhibition (60 mg kg, po; TGI=76%). The compound effectively reduced levels of AR-V7 and AR-FL by 77.3% at 1 μM and 72.0% at 5 μM, respectively, in VCaP and LNCaP cell lines [1].

Thailanstatin D, an analogue of Thailanstatin A, inhibits AR-V7 gene splicing by disrupting the interaction between U2AF65 and SAP155, hindering their binding to the polypyrimidine tract situated between the branch point and the 3' splice site. This compound displays potent tumor inhibitory properties in human castration-resistant prostate cancer (CRPC) xenografts, resulting in cellular apoptosis.

PF-05089771 is a voltage-gated sodium channel 1.7 (Nav1.7) blocker (IC50: 11, 16, 33, and 20 nM for 5N11S, 5A11L, 5A11S, and 5A11L Nav1.7 splice variants, respectively). It is selective for Nav1.7 over Nav1.1-1.6 and 1.8 channels (IC50: 0.11-25 μM), L-typ

VNPP433-3β acts as a molecular glue degrader, targeting the androgen receptor (AR) and its splice variants (AR-Vs) as well as MAP kinase-interacting serine threonine protein kinase Mnk1 2. It effectively inhibits the proliferation of cancer cells LNCaP, C4-2B, and CWR22Rv1, with GI50 values of 0.2, 0.3, and 0.31 μM, respectively. Additionally, VNPP433-3β shows favorable pharmacokinetics in CD-1 mice and suppresses tumor growth in the CWR22Rv1 xenograft mouse model.

Vercirnon (GSK1605786A) sodium is an orally bioavailable, selective, and potent CCR9 antagonist. It inhibits CCR9-mediated calcium mobilization and chemotaxis in Molt-4 cells with IC50 values of 5.4 nM and 3.4 nM, respectively. Vercirnon sodium demonstrates high selectivity, showing IC50 values exceeding 10 µM for CCR1-12 and CX3CR1-7 receptors. It also inhibits CCL25-directed chemotaxis in both CCR9 splice variants, CCR9A and CCR9B, with IC50 values of 2.8 nM and 2.6 nM, respectively.

Tyrosine kinase-IN-6 is a potent inhibitor of RON splice variants, exhibiting notable anticancer and antineoplastic effects [1].

3’-Me Meayamycin D is a splice modulator that targets SF3B1 and PHF5A, affecting the pre-mRNA splicing process and downregulating MCL-1 expression. It inhibits the proliferation of cancer cell lines HCT116, SW48, A549, DMS53, and DMS114, with a GI50 range of 4.6-7.2 nM. In mice, it demonstrates good plasma stability with a half-life of 16 hours.