Ask about this productRelated genes to: VPRBP antibody
- Gene:
- DCAF1 NIH gene
- Name:
- DDB1 and CUL4 associated factor 1
- Previous symbol:
- VPRBP
- Synonyms:
- KIAA0800, MGC102804
- Chromosome:
- 3p21.2
- Locus Type:
- gene with protein product
- Date approved:
- 2006-01-09
- Date modifiied:
- 2016-06-06
Related products to: VPRBP antibody
Related articles to: VPRBP antibody
- DCAF1 is a donut shaped WD40 repeat protein and a substrate receptor of two distinct E3 ligases. In HIV-1 infection, the viral protein Vpr binds to the top surface of DCAF1, changes its substrate specificity to degrade human proteins involved in antiviral activities, enabling HIV-1 to replicate. We hypothesized that artificial top-to-top self-dimerization of DCAF1 could result in DCAF1 loss-of-function and blocking of the Vpr-DCAF1 interaction. We designed and synthesized seven compounds we call SDIPTACs (Self-dimerization Induced Proximity Targeting Chimeras) which artificially induce DCAF1 self-dimerization through the Vpr interaction surface. Interestingly, SDIPTACs C8 and C9, inhibited Vpr-dependent HIV replication in CD4 T cells. Biophysical data and crystal structures of four DCAF1-SDIPTAC-DCAF1 ternary complexes revealed more details on DCAF1-DCAF1 complex stability, conformation, and their contribution to compound efficacy. Using SDIPTACs with unique mechanism may therefore be an efficient strategy in the development of future therapeutics for HIV infection and other diseases. - Source: PubMed
Publication date: 2026/05/18
Mabanglo Mark FSrivastava SmritiMatsui YusukeLi ZichongNoureldin MahmoudPogmore Justin PHoffer LaurentTaherian FatemehHajian TaranehTucker SarahMamai AhmedKiyota TairaAman AhmedAl-Awar RimaMarcellus RichardUehling David EOtt MelanieRamnauth JailallVedadi Masoud - Generative models enable large-scale exploration of chemical space; however, achieving controllable generation that balances novelty with preservation of bioactive features remains challenging. In this study, we introduce a controllable framework based on the VeGA architecture, leveraging SMARTS-RX functional descriptors. We present two distinct SMILES-based generative models: VeGA-RX, conditioned on semantic tokens for flexible exploration, and VeGA-SCX, which integrates topological guidance via Bemis-Murcko scaffolds for high-precision generation. We show that sampling temperature modulates chemical quality, with lower temperatures ( = 0.6) reducing structural alerts and improving drug-likeness without additional reinforcement learning (RL). Retrospective benchmarking on five pharmacological targets using a strict leakage-safe holdout strategy reveals a clear functional dichotomy: VeGA-SCX maximizes the recovery of bioactive chemotypes (e.g., >90% on mTORC1), while VeGA-RX effectively navigates complex chemical spaces with superior creativity. Comparative analysis against LDMol, a state-of-the-art text-to-molecule diffusion model, confirms the advantages of our autoregressive approach, which delivers higher chemical validity, stricter adherence to constraints, and significantly lower computational latency. In addition, we validate the framework in data-scarce scenarios targeting DCAF1 and WRN helicase, prioritizing candidate ligands exhibiting stable computational binding modes supported by docking and molecular dynamics simulations. Overall, this framework provides a controllable and interpretable strategy for precision-oriented generative chemistry. The complete workflow is open-source and available on GitHub. - Source: PubMed
Publication date: 2026/04/16
Delre PietroBellofatto GiadaLavecchia Antonio - Pentatropis capensis (L.f.) Bullock (Apocynaceae) is traditionally used to treat various ailments. However, it lacks systematic scientific validation. This study investigated the phytochemical composition and biological activities of methanolic, ethyl acetate, and hexane leaf extracts. Among them, the methanolic extract showed the highest extractive yield as well as the greatest phenolic (16.5 mg GAE/g) and flavonoid (20 mg QE/g) contents. It also exhibited strong antioxidant activity (DPPH IC = 14.85 µg/mL; ABTS IC = 26.13 µg/mL; TAC OD = 0.18), notable antibacterial efficacy against Staphylococcus aureus (22 ± 0.3 mm; MIC = 24 µg/mL), and significant anti-inflammatory activity (protein denaturation IC = 12.81 µg/mL). The methanolic extract also demonstrated the highest cytotoxicity against HT-29 colon cancer cells (IC = 65.62 µg/mL). Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS) analyses identified key bioactive compounds. Molecular docking revealed strong binding affinities of major constituents, particularly octadecanedioic acid, cyclohexane derivatives, and n-octacosanol, toward the colorectal cancer target DCAF1/VprBP (3WA0). Further validation through a 100 ns molecular dynamics simulation and MM-PBSA analysis confirmed stable binding with minimal RMSD fluctuations. Overall, these findings highlight the therapeutic potential of P. capensis and support its further in vivo evaluation for cancer treatment. - Source: PubMed
Ganesan LavanyaKumaravel Sri KalpanaPackiaraj GurusaravananMaluventhen VijiPitchai MuruganBalamuralikrishnan BalasubramanianArumugam Maruthupandian - PROteolysis TArgeting Chimera (PROTAC) is a promising modality for targeted protein degradation. Although 600+ E3 ligases exist in the human genome, most PROTACs exploit a very limited set of E3 ligases, primarily CRBN and VHL. In this study, we designed, synthesized and evaluated a series of KRAS-G12D degraders that recruit one of four E3 ligases (CRBN, VHL, DCAF1, or KLHDC2) using a common KRAS-G12D binder derived from the KRAS-G12D inhibitor MRTX1133. Through this structure-activity relationship (SAR) study, we discovered two potent degraders: 30 (CRBN-based) and 41 (VHL-based), both of which effectively degraded KRAS-G12D and suppressed downstream signaling. By introducing a triazole-based VHL ligand, we subsequently discovered 43, which showed improved degradation and antiproliferative activity comparable to a previously reported KRAS-G12D degrader. In contrast, KLHDC2- and DCAF1-based degraders failed to induce KRAS-G12D degradation, potentially due to suboptimal ternary complex formation or insufficient E3 ligase compatibility. These findings highlight the importance of E3 ligase selection in the development of effective KRAS-G12D degraders. - Source: PubMed
Publication date: 2026/02/03
Yim HyerinSong XiangyangZhong YueHu JacquelineXiong YanJin Jian - Pancreatic cancer is a common malignant tumor of the digestive tract characterized by high mortality, primarily due to its aggressive proliferation and metastasis. DDB1-CUL4-associated factor 1 (DCAF1) has recently been identified as a cancer ‒ promoting gene in hepatocellular carcinoma and melanoma. However, its role and mechanism of action in pancreatic cancer remain largely unexplored. Analysis of the GEPIA database and experimental validation revealed that DCAF1 is significantly overexpressed in pancreatic cancer tissues and cell lines. Functional assays demonstrated that DCAF1 knockdown inhibited the proliferation, invasion, and migration of pancreatic cancer cells. Moreover, DCAF1 suppression impeded EMT, as evidenced by decreased expression of mesenchymal markers N-cadherin and α-SMA and increased expression of the epithelial marker E-cadherin. Knockdown of DCAF1 can inhibit Phosphatase and Tensin Homolog (PTEN) ubiquitination, leading to inactivation of the PI3K/Akt signaling pathway. In addition, the use of IGF-1 in the replenishment experiment can reverse the effect of knockdown of DCAF1, suggesting that DCAF1 may promote pancreatic cancer metastasis by activating this pathway. These findings suggest that DCAF1 functions as an oncogene in pancreatic cancer, promoting cell proliferation, migration, invasion, and EMT through activation of the PTEN/PI3K/Akt signaling pathway. - Source: PubMed
Wang JiaweiWu YifenXu WenyiRuan Qingqing