Ask about this productRelated genes to: SLFN12 Blocking Peptide
- Gene:
- SLFN12 NIH gene
- Name:
- schlafen family member 12
- Previous symbol:
- -
- Synonyms:
- FLJ10260
- Chromosome:
- 17q12
- Locus Type:
- gene with protein product
- Date approved:
- 2006-04-05
- Date modifiied:
- 2019-03-19
Related products to: SLFN12 Blocking Peptide
Related articles to: SLFN12 Blocking Peptide
- Organophosphate esters (OPEs) are widely used flame retardants and plasticizers prevalent in indoor air, dust, and water. Studies suggest prenatal OPE exposure is linked to adverse maternal and infant outcomes, but the biological mechanisms remain unclear. - Source: PubMed
Publication date: 2026/07/03
Tang WanyiFoley HelenYang XiaoranMohazzab-Hosseinian SahraYang TingyuHernandez-Castro IxelKannan KurunthachalamXiang YijinMi HuaiyuWiemels JosephLewinger Juan PabloSiegmund KimberlyBastain TheresaBreton CarrieShu Chang - Velcrin compounds kill cancer cells expressing elevated levels of two cellular proteins, the PDE3A phosphodiesterase and the SLFN12 tRNase, by inducing PDE3A-SLFN12 complex formation. This results in activation of SLFN12, leading to digestion of its specific substrate, tRNA-Leu-TAA, inhibition of protein synthesis, and cell death, a process now called "tomoptosis". We hypothesized that velcrins such as BAY 2666605, a clinical velcrin, could be active against biomarker-positive uveal melanomas. We identified uveal melanoma cell lines expressing elevated levels of the biomarkers, PDE3A and SLFN12, and tested response to velcrin compounds in vitro and in vivo. We show that response correlates mechanistically with decreased levels of tRNA-Leu-TAA and inhibition of nascent protein synthesis and furthermore identify a potential mechanism of resistance. - Source: PubMed
Publication date: 2026/06/02
Kotýnková KristýnaAndersen SawyerDenney DanielKarsli Uzunbas GizemBurri MilesWu XiaoyunKaplan BethanyHaq RizwanMeyerson MatthewGreulich Heidi - Phosphodiesterase 3 A (PDE3A) is a well-characterized enzyme that plays a crucial role in various cellular processes, including cAMP-mediated signaling, CREB-mediated induction of p21 and signaling through protein kinases A and G. PDE3A has also been suggested as an inflammation-associated stemness gene which upon interaction with protein SLFN12, leads to blocked protein translation and induction of apoptosis. PDE3A has been found to be highly expressed in several human cancer types including sarcomas, pancreatic ductal adenocarcinoma, non-small cell lung cancer and melanoma. PDE3A has thus emerged as a potential therapeutic cancer target. However, to fully understand the functional role and validate target potential of PDE3A in different human cancers, further research is needed. We report here a pan-cancer ex vivo study of PDE3A protein expression across 24 different cancer types represented by 59 different molecular subtypes correlated with ex vivo drug screening of PDE3A-SLFN12 molecular glue anagrelide in 250 patient derived functional tumor models. Results of the study identify highest PDE3A expression in melanomas and across different histological subtypes of sarcomas. Correlating with the expression profile of PDE3A, anagrelide was found to display best therapeutic potential in sarcomas with high protein expression of both PDE3A and SLFN12, though sarcoma heterogeneity warrants further subtype-specific validation. - Source: PubMed
Publication date: 2026/04/28
Rice KieshaLehtinen NooraVälimäki EetuSuhonen JanneTaimen PekkaKettunen KimmoVentelä SamiKononen JuhaSihto HarriRantala Juha K - PDE3A is a key member of the cyclic nucleotide phosphodiesterase family. By modulating intracellular cAMP and cGMP levels, it participates in diverse physiological processes such as platelet activation, cardiac function, oocyte maturation, and vascular smooth muscle cell proliferation. Recent studies have revealed that PDE3A also plays critical roles in multiple malignant tumors. This study aims to investigate the regulation of PDE3A expression, its role in cancer, and its potential as a therapeutic target, with a particular focus on its impact on tumor cell proliferation, metastasis, and resistance to chemotherapy. - Source: PubMed
Publication date: 2026/02/05
Pu ShengyuZhang QiheMiao MiChen BohongXu JiaruiLei JingyiTang XiaojiangHao Na - We examined the role of SLFN12, a member of the Schlafen (SLFN) family of interferon-regulated genes and proteins in leukemogenesis, and its potential as a therapeutic target in acute myeloid leukemia (AML). We explored the effects of velcrins, a class of small molecules able to modulate SLFN12 biological activity, on AML cells. Velcrin treatment of AML cells stabilized SLFN12 and promoted SLFN12 complex formation with phosphodiesterase 3A or phosphodiesterase 3B. Such effects were associated with growth-inhibitory and proapoptotic responses, as well as potent suppressive effects on leukemic cell growth. In addition, velcrin treatment suppressed clonogenic capacity of primitive leukemic progenitors and significantly extended survival in a mouse AML xenograft model. Taken together, these findings establish an important role of SLFN12 in leukemogenesis and raise the potential for the use of velcrins as a therapeutic strategy for AML. - Source: PubMed
Guillen Magaña Jamie NZannikou MarkellaBaran AnetaSmall SaraSchieber MichaelSchipma Matthew JBartom Elizabeth TKocherginsky MashaSaleiro DianaBeauchamp Elspeth MEckerdt FrankPlatanias Leonidas C