Journal: bioRxiv

Article Title: Inhibition of Stearoyl-CoA desaturase suppresses follicular help T and germinal center B cell responses

doi: 10.1101/601021

Figure Lengend Snippet: (A-B) Frequencies and absolute cell number of splenic T FH and GC B cells in the mice immunized with X31 virus and treated with SCD1 inhibitor at indicated d.p.i. (n = 7 - 10). (C) Frequency of splenic T FR and T FH cells were measured in the in the mice immunized with X31 virus and treated with SCD1 inhibitor at 14 d.p.i. (D) The titer of influenza-specific IgG was measured by ELISA from blood serum at 14 d.p.i. Representative data are obtained from at 3 independent experiments. * indicates significant differences ( P <0.05) between DMSO control group and SCD inhibitor (A939572) treated group.

Article Snippet: A939572 (6 mg/kg, BioFine International, WA, USA), C75 (15 mg/kg, Cayman chemical, MI, USA) or of Fluvastatin (20mg/kg, Cayman chemical) was injected to the X31 immunized mice from day 4 to day 13 for daily via intraperitoneal route.

Techniques: Enzyme-linked Immunosorbent Assay

Journal: Cell Death & Disease

Article Title: Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells

doi: 10.1038/cddis.2013.444

Figure Lengend Snippet: SCD1 is overexpressed in lung spheroid cultures. ( a ) ALDH1A1 activity was measured by flow cytometry, as described in Materials and Methods, in spheroid cultures obtained from five lung primary cell cultures and a stable cell line. Results indicated an increased ALDH1A1 activity in Pe d/10 (13.5%), Pe e/10 (11.5%), Pe o/11 (25.1%) and NCI-H460 (22.5%) spheroids. Results represent the means±S.D. of three independent experiments. ( b ) Spheroid-forming ability was also evaluated using different cell density in serum-free medium supplemented with growth factors for 8 days. Increased spherogenicity was observed in spheroid cultures obtained from three primary cell cultures and in the stable cell line NCI-H460, which also displayed increased ALDH1A1 activity. Results are the means of three independent experiments; bars indicate S.D. ( c ) SCD1 mRNA level was increased more than 10-fold in spheroids cultures compared with adherent cultures. Results represented in the histogram are the means±S.D. of three independent experiments. GAPDH was used as housekeeping gene. Student's t -test * P <0.01 and ** P <0.05 in adherent versus spheroid cell cultures. ( d ) Representative western blotting showing SCD1 protein expression upregulation in three primary cultures and the stable cell line NCI-H460 grown as spheroid in respect to adherent cultures. GAPDH was used as loading control

Article Snippet: Although untreated cultures displayed a typical spheroid pattern of growth, characterized by sphericity of the multicellular structures ( =0.92) and high percentage of tight spheroids (exceeding 50%) ( , ), the amount of tight spheroids in the presence of the SCD1 inhibitor was drastically reduced (10.3% Chi square test: P <0.0001) and the cultures were characterized by high prevalence of irregular cell aggregates (62.8%) of lower sphericity ( =0.80) with respect to the untreated cultures ( ).

Techniques: Activity Assay, Flow Cytometry, Stable Transfection, Western Blot, Expressing, Control

Journal: Cell Death & Disease

Article Title: Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells

doi: 10.1038/cddis.2013.444

Figure Lengend Snippet: Silencing and pharmacological inhibition of SCD1 reduces the capability to form spheroids. ( a ) Spheroid-forming ability was reduced in NCI-H460, Pe d/10, Pe o/11 cell cultures after transfection with SCD1 siRNA, compared with control siRNA (scramble). Spheroids were allowed to form as described previously in Materials and methods, and were counted by optical microscopy. Results are the means±S.D. of three independent experiments. Student's t -test * P <0.01, ** P <0.05 in scramble versus siSCD1-transfected cells. ( b ) Representative western blotting of SCD1 protein expression was performed in siSCD1 and scramble-transfected cultures. GAPDH was used as normalization. ( c ) Spheroid-forming assay was carried out in NCI-H460 and Pe o/11 cell cultures treated with the indicated concentration of MF-438; results showed a decreased spheroid formation in the presence of increased concentration of the inhibitor. Results are the means of three independent experiments where bars indicate S.D. ( d ) A concentration of 1 μ M oleic acid-BSA can rescue the inhibitory effect of MF-438 when added to NCI-H460 spheroids in a spheroid-forming assay. Data are means±S.D. of three independent experiments

Article Snippet: Although untreated cultures displayed a typical spheroid pattern of growth, characterized by sphericity of the multicellular structures ( =0.92) and high percentage of tight spheroids (exceeding 50%) ( , ), the amount of tight spheroids in the presence of the SCD1 inhibitor was drastically reduced (10.3% Chi square test: P <0.0001) and the cultures were characterized by high prevalence of irregular cell aggregates (62.8%) of lower sphericity ( =0.80) with respect to the untreated cultures ( ).

Techniques: Inhibition, Transfection, Control, Microscopy, Western Blot, Expressing, Concentration Assay

Journal: Cell Death & Disease

Article Title: Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells

doi: 10.1038/cddis.2013.444

Figure Lengend Snippet: Three-dimensional and morphometric analysis of Pe o/11 tumor spheroids grown with or without SCD1 inhibitor. ( a ) Differential interference contrast microscopy of Pe o/11 cultures. The untreated Pe o/11 cultures (left panel) exhibited a typical spheroid pattern of growth with many densely packed spheres with indiscernible individual cells (see inset). The Pe o/11 cultures grown in presence of SCD1 inhibitor for 72 h were characterized by a high number of irregular multicellular structures (right panel) and displayed a small amount of tight spheroids. ( b ) Morphometric analysis of all multicellular structures from treated or untreated Pe o/11: the box-and-whisker plot of shape factor showed the higher sphericity of the tumor spheroids obtained from Pe o/11-untreated cultures. The central box represents the interquartile ranges, the middle line represents the median and the horizontal lines represent the minimum and the maximum value of observation range (Mann–Whitney test: * P <0.0001). At the morphological categorization of structures (see histogram), untreated Pe o/11 showed a higher prevalence of tight spheroids (51.4% versus 10.3%) and a lower prevalence of irregular aggregated (26.9% versus 62.8%) compared with treated Pe o/11. Results reported in graph represent the mean values±S.E. of three experimental replicates (chi-square test: ** P <0.0001). ( c ) Morphometric analysis of tight spheroids from treated or untreated Pe o/11: the box-and-whisker plots of size and SCF volume (see Materials and methods) showed that untreated cultures were characterized by a higher size and volume of tight spheroids respect to the treated cultures (Mann–Whitney test: *** P <0.001)

Article Snippet: Although untreated cultures displayed a typical spheroid pattern of growth, characterized by sphericity of the multicellular structures ( =0.92) and high percentage of tight spheroids (exceeding 50%) ( , ), the amount of tight spheroids in the presence of the SCD1 inhibitor was drastically reduced (10.3% Chi square test: P <0.0001) and the cultures were characterized by high prevalence of irregular cell aggregates (62.8%) of lower sphericity ( =0.80) with respect to the untreated cultures ( ).

Techniques: Microscopy, Whisker Assay, MANN-WHITNEY

Journal: Cell Death & Disease

Article Title: Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells

doi: 10.1038/cddis.2013.444

Figure Lengend Snippet: SCD1 inhibition reduces markers of staminality. ( a ) Pictures of ALDH1A1 activity determined by flow cytometry using Aldefluor assay. NCI-H460 and Pe o/11 cells were transfected with control siRNA (scramble) or a siRNA specific for SCD1 (siSCD1), cultured for 72 h in spheroid medium and subjected to ALDHA1A activity assay by flow cytometry. Data indicated that silencing of SCD1 reduced dramatically the percentage of cells with ALDH1A1 activity both in NCI-H460 and Pe o/11 cultures. Data are representative of three independent experiments. ( b ) RT-real time PCR was performed to evaluate mRNA relative expressions of OCT4 and Nanog in siSCD1 and scramble-transfected NCI-H460 cell cultures. Results demonstrated a decreased in mRNA levels of both OCT4 and Nanog genes in siSCD1-transfected cells in respect to control siRNA-transfected spheroids. Histograms show the means of at least three independent experiments. Bars indicate S.D. Student's t -test * P <0.01 in siSCD1 versus control siRNA-transfected cells. GAPDH was used as the normalization. ( c ) Representative pictures of flow cytometry analysis for ALDH1A1 activity. Spheroids of Pe o/11 and NCI-H460 cell cultures treated for 72 h with MF-438 (1 μ M) reduced the percentage of positive cells with ALDH1A1 activity. Data are representative of three independent experiments

Article Snippet: Although untreated cultures displayed a typical spheroid pattern of growth, characterized by sphericity of the multicellular structures ( =0.92) and high percentage of tight spheroids (exceeding 50%) ( , ), the amount of tight spheroids in the presence of the SCD1 inhibitor was drastically reduced (10.3% Chi square test: P <0.0001) and the cultures were characterized by high prevalence of irregular cell aggregates (62.8%) of lower sphericity ( =0.80) with respect to the untreated cultures ( ).

Techniques: Inhibition, Activity Assay, Flow Cytometry, Transfection, Control, Cell Culture, Real-time Polymerase Chain Reaction

Journal: Cell Death & Disease

Article Title: Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells

doi: 10.1038/cddis.2013.444

Figure Lengend Snippet: MF-438 induces apoptosis and cellular damage in Pe o/11 spheroids. ( a ) Flow cytometry analysis using Annexin V staining, showed apoptosis induction in Pe o/11 spheroids treated for 72 h with MF-438 (1 μ M). Data shown in the histogram are the means of three independent experiments, where bars represent S.D. * P <0.01 in treated versus untreated spheroids. ( b ) Analysis of ultrastructural features demonstrated that Pe o/11-untreated spheroids (left panel) showed nuclei generally rounded or, occasionally lobulated, with chromatin finely dispersed and prominent nucleoli. The cytoplasm displayed numerous mitochondria, rod-shaped or elongated, and variable amounts of organelles. Pe o/11-treated cells (right panel) exhibit cellular damage findings such as cytoplasmatic vacuolization, mitochondrial swelling, apoptotic nuclei with areas of marginal, dense-staining chromatin (see asterisk) and, although less frequently, nuclear and cellular fragmentation. Both spheroid cultures, undergone or not to MF-438 treatment, did not exhibit classical junctional complex but rather few continuous junctions and displayed discontinuous and short surface microvilli. (TEM, uranyl acetate/lead citrate). ( c ) Upper panel: Pe o/11 cultures were treated or not with MF-438 1 μ M as described above and immunostained with M30 CytoDEATH Fluorescein monoclonal antibody, able to detect the caspase-cleaved cytokeratin 18. Quantitative immunofluorescence analysis indicated that the percentage of cells presenting positive M30 signal was higher in Pe o/11-treated cultures (47.3% versus 2.4% * P <0.0001). Lower panel: the co-immunostaining for M30 and the stemness marker ALDH1A1 showed that the treatment with MF-438 induced a decrease in ALDH1A1-positive cells (66.8% versus 86.2% obtained from untreated spheroids; Student's t -test: ** P <0.05) and that the SCD1 inhibitor selectively killed the cells with stem-like properties, in fact most of the apoptotic M30 positive cells were also positive for ALDH1A1 (31.6% of M30 + /AldhA1 + versus 3.0% of M30 + /AldhA1 − cells in Pe o/11 MF-438 treated; Student's t -test: * P <0.0001). Data represent the means of three independent experiments. Bars indicate S.D.

Article Snippet: Although untreated cultures displayed a typical spheroid pattern of growth, characterized by sphericity of the multicellular structures ( =0.92) and high percentage of tight spheroids (exceeding 50%) ( , ), the amount of tight spheroids in the presence of the SCD1 inhibitor was drastically reduced (10.3% Chi square test: P <0.0001) and the cultures were characterized by high prevalence of irregular cell aggregates (62.8%) of lower sphericity ( =0.80) with respect to the untreated cultures ( ).

Techniques: Flow Cytometry, Staining, Immunofluorescence, Immunostaining, Marker

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: (A) Structure of Aramchol (B) SCD1 converts saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs), inhibiting SCD1 results in decreased incorporation of lipid droplets, reduced lipid storage and increased fatty acid oxidation.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: General structural representation of SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Monocyclic SCD1 inhibitors: piperazinyl – pyridazine based SCD1 inhibitors as reported by Xenon.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Monocyclic SCD1 inhibitors: six-membered piperazinyl based SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Monocyclic SCD1 inhibitors: pyridazine based carboxamide and acetylene linker containing SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Monocyclic SCD1 inhibitors: piperidine based SSI-4 and pyridine based SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Monocyclic SCD1 inhibitors: pyridazine–piperidine containing SCD1 inhibitors reported by Takeda Pharmaceuticals and Yang et al.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Monocyclic SCD1 inhibitors: SCD1 inhibitors reported by Xenon and Merck.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Monocyclic SCD1 inhibitors: SCD1 inhibitors containing 5-membered rings as central moiety.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Monocyclic SCD1 inhibitors: thiazole derivatives as SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Monocyclic SCD1 inhibitors: five membered heterocycles reported for SCD1 inhibition.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques: Inhibition

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Bicyclic SCD1 inhibitors: development of SAR 707 and SAR 224.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Bicyclic SCD1 inhibitors: various bicyclic heterocycles as potential SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Spirocyclic SCD1 inhibitors: spiro benzo-oxapine based SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Spirocyclic SCD1 inhibitors: oxazepane-piperidine based spirocyclic systemic SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Development of MK-8245 based SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Tetrazole and thiazole acetic acid based SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Acyclic linker based liver targeted SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Spirocyclic liver targeted SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Natural products based SCD1 inhibitors.

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques:

Journal: RSC Advances

Article Title: An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

doi: 10.1039/d4ra06237j

Figure Lengend Snippet: Key developments in SCD1 inhibitors during the last 10 years (2013–2023)

Article Snippet: Medicis Pharmaceuticals reported a simple phenoxy pyrrolidine potent SCD1 inhibitor compound 76 , with aromatic rings substituted at either end and pyrrolidine as central ring.

Techniques: Activity Assay, Inhibition, Binding Assay, In Silico