Ask about this productRelated genes to: FGD1 Blocking Peptide
- Gene:
- FGD1 NIH gene
- Name:
- FYVE, RhoGEF and PH domain containing 1
- Previous symbol:
- FGDY
- Synonyms:
- ZFYVE3
- Chromosome:
- Xp11.22
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2016-10-05
Related products to: FGD1 Blocking Peptide
Related articles to: FGD1 Blocking Peptide
- Tuberculosis (TB) remains a major global health problem, and treatment progress is increasingly threatened by rising multidrug-resistant tuberculosis (MDR-TB). Delamanid (DLM), a nitroimidazole drug, has shown good efficacy and safety against both drug-susceptible and drug-resistant () strains. However, data on its resistance mechanisms, drug susceptibility testing (DST), clinical effectiveness, safety, and pharmacokinetics remain limited. This review aims to summarize the most recent molecular, structural, and clinical evidence related to DLM. - Source: PubMed
Publication date: 2026/05/04
Islam Md MahmudulHasan Md ZahidTusar Md Touki TahamidHossain Md YeaminHossain Md MotaherJubayed Md Abdulla AlJubaer-Al-Abedin MdSoikot SheikhAkther ShanzidaBhuyian JahidGazi Hafizur RahmanHasan B M MahmudulAzam Md ShofiulHaque Md EnamulAbdullah-Al-Jubayer Hasan Md FarukHaydar F M AliKhalekuzzaman MdIslam Md TorequlHasan Sohel - MDR TB treatment is now facing the perils of emerging resistance to BDQ(bedaquiline) and DLM(delaminid). Both DLM and PRT(pretomanid) belong to the nitroimidazole group of drugs. Drug resistance in Mycobacterium Tuberculosis (MTB) is an ever changing, continuous and evolving process whereby the bacteria finds new genetic mutations to escape destruction by the newer drugs. DLM and PRT belong to the same class of drugs and resistance to both drugs have been described with mutations in five M. tuberculosis genes (ddn, fgd1, fbiA, fbiB, and fbiC) resulting in very high level of cross-resistance between the two drugs. Mutations in Rv2983 (fbiD), fbiB genes and some ddn allelles (S78Y, Y133C) can cause resistance to PRT but the strains may retain susceptibility to DLM. These reasons may lead to slight preference for DLM as compared to PRT. Such implications may be also kept in mind while treatment of MDR-TB with DLM and PRT. - Source: PubMed
Publication date: 2025/09/20
Sharma AmitChatterjee PoulomiShastry Shashank - Delamanid and Pretomanid are nitro-dihydro-imidazooxazole derivatives essential for the treatment of multidrug-resistant tuberculosis (MDR-TB). The emergence of tuberculosis resistance to Delamanid necessitates understanding the molecular mechanisms underlying this resistance. This study focuses on the structural analysis of the fgd1 protein in both wild-type and mutant forms to explain the molecular basis of Delamanid resistance. Since the fgd1 complex with the F420 cofactor is responsible for the activation of Delamanid, we investigated the impact of mutations on the structural stability, primarily using molecular dynamics simulations, and electronic properties using quantum mechanics/molecular mechanics (QM/MM) studies of the fgd1-F420 complex. Among the pool of available mutants, we selected 12 fgd1 mutants (K9A, L70R, G71D, Q88E, M93R, N112K, A176D, G191D, K198A, E230K, W284S, and G314E) that exhibited resistance to Delamanid. A significant change in the protein and cofactor conformation was observed in some mutants compared to that in the wild-type, with increased RMSD and RMSF. To further analyze the binding affinity between fgd1-F420 WT and the mutants in detail, we performed MM-GBSA calculations and observed reduced F420 binding for K9A, G71D, N112K, K198A, and W284S mutations. Additionally, QM/MM calculations demonstrated how mutations influenced the electronic environment of fgd1, indicating that all mutations, except K9A, led to reduced stability. These alterations suggest that mutations may alter the local electronic environment, potentially affecting the cofactor binding and catalytic processes. Overall, these results provide new structural insights and vital clues for designing novel inhibitors to combat nitroimidazole resistance. - Source: PubMed
Publication date: 2026/03/27
Saxena ShaliniGuruprasad Lalitha - Multidrug-resistant tuberculosis (MDR-TB) remains a major global health threat. Delamanid (DLM) and pretomanid (PMD) are core drugs in new multidrug-resistant tuberculosis regimens, but the spectrum of their resistance mutations is poorly defined. - Source: PubMed
Publication date: 2026/03/23
Zhang QianXu PengZhang XuecongPi RuiChen YiwangTakiff HowardGao Qian - FGD1 is an X-linked gene and acts as a guanine nucleotide exchange factor that activates guanosine triphosphatase Cdc42 and influences cell cycle progression, cell morphology, motility, and extracellular matrix degradation. In this study, we aim to understand FGD1 function in melanoma to better understand the correlation between poor survival and high FGD1 expression identified in The Cancer Genome Atlas messenger RNA data, especially in patients with BRAF mutations. FGD1 knockdown in BRAF V600E-mutated melanoma cell lines reduces cell proliferation and induces secondary resistance to BRAF inhibition, while increasing sensitivity to p21-activated kinase inhibition. Markedly, when FGD1 knockdown becomes ineffective, resistant cells not only restore endogenous FGD1 expression but also exhibit upregulation of epidermal growth factor receptor and phospho-p21-activated kinase, both known markers of BRAF inhibition resistance, highlighting a shift toward an adaptive resistance phenotype. Furthermore, we show that secondary resistance induced by prolonged exposure of melanoma cells to BRAF inhibitor is associated with reduced FGD1 levels. These findings highlight the importance of FGD1 in melanoma progression and the acquisition of secondary resistance, positioning the FGD1 -mediated signaling pathway as a putative therapeutic target. - Source: PubMed
Publication date: 2026/04/28
Namir GuyElchebly MounibPapadakis Andreas ISpatz Alan