tp 10 mg kg  (MedChemExpress)

Journal: Annals of Hematology

Article Title: BCOR mutations define a therapeutic vulnerability to DHODH Inhibition in acute myeloid leukemia

doi: 10.1007/s00277-026-06773-z

Figure Lengend Snippet: BCOR deficiency sensitizes cells to DHODH Inhibitors. ( A ) Heatmaps representing survival fractions of OCI-AML2, OCI-AML3 and RPE1 treated with increasing doses of TP-021 (BCOR inhibitor) and brequinar, for 6 days ( n = 3 per line). Survival fractions of OCI-AML2, OCI-AML3 and RPE1 treated with working dose of TP-021 (10 µM) compared to DMSO, with increasing doses of brequinar, for each cell line, for 6 days (two-way ANOVA, n = 3; p < 0.0001****; p < 0.001***). ( B ) Survival fractions of OCI-AML2, OCI-AML3 and RPE1; transfected with siRNA and ± treated with brequinar 1 µM (two-way ANOVA, n = 3; p < 0.0001****). ( C ) Cell proliferation assay of RPE1 transfected with siRNA, ± treated with brequinar 1 µM (two-way ANOVA, n = 2; p < 0.0001****) with ( D ) associated pictures taken at 48 h (basic analyzer – Incucyte, 10x magnification). (E) SKM-1 (BCOR-mutated AML) was treated with increasing doses of DHODH inhibitors for 6 days (two-way ANOVA, n = 3; p < 0.0001****). ( F ) OCI-AML3 BCOR_WT , OCI-AML3 BCOR_KO.03 , OCI-AML3 BCOR_KO.17 and OCI-AML3 BCOR_KO.24 were treated for 6 days with increasing doses of 5 different DHODH inhibitors (two-way ANOVA, n = 3; p < 0.0001****, p < 0.001***, p < 0.01**, p < 0.05*, n.s = non-significant)

Article Snippet: For pharmacologic studies, cells were treated with brequinar (Cayman Chemical), TP-021, leflunomide, teriflunomide, AG-636, farudodstat, sparfosic acid (MedChemExpress), or 6-azauridine (Thermo Fisher).

Techniques: Transfection, Proliferation Assay

Journal: NAR Molecular Medicine

Article Title: Inhibitory effects of molnupiravir on Crimean–Congo hemorrhagic fever virus polymerase

doi: 10.1093/narmme/ugaf041

Figure Lengend Snippet: CCHFV and LASV L protein RNA synthesis patterns succeeding a single NHC-monophosphate. ( A ) RNA primer/template that supports incorporation of single CMP or NHC-monophosphate as a C-analog at position 6. RNA synthesis products catalyzed by CCHFV ( B ) and LASV ( C ) L protein. G indicates incorporation of [α- 32 P]-GTP at position 5. A 5′- 32 P-labeled 4-nt primer (4) serves as a size marker ( m ). The numbers on the side of the gel image indicate the size of the products in nucleotides. The asterisk indicates products that are likely the result of sequence-dependent template slippage events. ( D ) Graphical representation of the incorporation of CTP and NHC-TP by CCHFV L protein when 0 µM ATP is present in the reaction mixture. ( E ) Graphical representation of the incorporation of CTP and NHC-TP by LASV L protein when 0 µM ATP is present in the reaction mixture. Here, the signal at position 6 is presented as a percentage of the total signal generated between positions 5 and 7.

Article Snippet: NHC-TP was purchased from MedChemExpress (HY-135867A), and NTPs were purchased from GE Healthcare.

Techniques: Labeling, Marker, Sequencing, Generated

Journal: NAR Molecular Medicine

Article Title: Inhibitory effects of molnupiravir on Crimean–Congo hemorrhagic fever virus polymerase

doi: 10.1093/narmme/ugaf041

Figure Lengend Snippet: AlphaFold model prediction of CCHFV RdRp domain bound to dsRNA and incorporating NHC-TP. ( A ) The molecular surface (transparent beige) of the AlphaFold-predicted full-length CCHFV L-protein; the polymerase domain, including the subdomains thumb (green), palm (orange), and fingers (blue), is highlighted and individually displayed in ( B ). The gray region constitutes an undefined region. ( C ) A model of the RdRp domain in the complex with dsRNA substrate, primer strand (light blue), and template strand (green) shows the binding of NHC-TP as a substrate at the active site. ( D ) A close-up view of the active site, showing the potential interactions of NHC-TP with surrounding protein atoms and a Mg 2+ cofactor. Arg-2280 forms a potentially conserved interaction with the incoming NTP, analogous to that observed in SARS-CoV-2 RdRp structure . Gln-2275 is located within motif F , which appears to interact with the hydroxylamine on NHC-TP.

Article Snippet: NHC-TP was purchased from MedChemExpress (HY-135867A), and NTPs were purchased from GE Healthcare.

Techniques: Binding Assay