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Takeda small-molecule ask1 inhibitors
Small Molecule Ask1 Inhibitors, supplied by Takeda, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/small-molecule+ask1+inhibitors/pm40117753-24-2-0?v=Takeda
Average 90 stars, based on 1 article reviews

small-molecule ask1 inhibitors - by Bioz Stars, 2026-08

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(A) Groups of WT and CC1-KO livers were stored in UW solution (4°C/18 hours). Liver samples were collected right after cold storage (before OLT) or 3 hours after reperfusion (post-OLT). (B and C) Western blot–assisted detection and relative intensity ratio of cleaved caspase-3, RIP3, CC1, ASK1, p-p38 in naive liver, cold-stored liver or postreperfusion OLT (WT). Vinculin (VCL) expression served as an internal control and was used for normalization (n = 3/group). (D) Western blot–assisted detection and relative intensity ratio of CC1, ASK1, and p-p38 in naive WT or CC1-KO liver. VCL expression served as an internal control and was used for normalization (n = 4/group). (E) Western blot–assisted detection and relative intensity ratio of CC1, ASK1, and p-p38 in cold-stored WT or CC1-KO livers. VCL expression served as an internal control and used for normalization (n = 3/group). Data shown as mean ± SD. *P < 0.05, 1-way ANOVA followed by Tukey’s HSD test (B and C) or Student’s t test (D and E).

Journal: The Journal of Clinical Investigation

Article Title: Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury

doi: 10.1172/JCI133142

Figure Lengend Snippet: (A) Groups of WT and CC1-KO livers were stored in UW solution (4°C/18 hours). Liver samples were collected right after cold storage (before OLT) or 3 hours after reperfusion (post-OLT). (B and C) Western blot–assisted detection and relative intensity ratio of cleaved caspase-3, RIP3, CC1, ASK1, p-p38 in naive liver, cold-stored liver or postreperfusion OLT (WT). Vinculin (VCL) expression served as an internal control and was used for normalization (n = 3/group). (D) Western blot–assisted detection and relative intensity ratio of CC1, ASK1, and p-p38 in naive WT or CC1-KO liver. VCL expression served as an internal control and was used for normalization (n = 4/group). (E) Western blot–assisted detection and relative intensity ratio of CC1, ASK1, and p-p38 in cold-stored WT or CC1-KO livers. VCL expression served as an internal control and used for normalization (n = 3/group). Data shown as mean ± SD. *P < 0.05, 1-way ANOVA followed by Tukey’s HSD test (B and C) or Student’s t test (D and E).

Article Snippet: In separate experiments, donor livers were incubated with ASK1-specific small molecule inhibitor (10 μg/15 mL, MSC2032964A, R&D Systems) throughout 18 hours of cold storage.

Techniques: Western Blot, Expressing

(A) Primary mouse hepatocytes (WT) with or without cold stimulation (4°C/4 hours) were incubated for the indicated time periods. Western blot–assisted detection and relative intensity ratio of CC1, ASK1, p-p38. VCL expression served as an internal control and used for normalization (n = 2/group). (B–D) Cold-stimulated WT or CC1-KO hepatocytes were pretreated with or without siRNA against ASK1. (B) Western blot–assisted detection and relative intensity ratio of CC1, ASK1, p-p38. VCL expression served as an internal control and used for normalization (n = 3/group). (C) Representative (n = 3/group) immunohistochemical staining of 4HNE (red, upper panels), HMGB1 (red, middle panels), and dead cell detection (red, lower panels). (D) Quantification of dead cells/HPF (n = 4–5/group). *P < 0.05, 1-way ANOVA followed by Tukey’s HSD test.

Journal: The Journal of Clinical Investigation

Article Title: Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury

doi: 10.1172/JCI133142

Figure Lengend Snippet: (A) Primary mouse hepatocytes (WT) with or without cold stimulation (4°C/4 hours) were incubated for the indicated time periods. Western blot–assisted detection and relative intensity ratio of CC1, ASK1, p-p38. VCL expression served as an internal control and used for normalization (n = 2/group). (B–D) Cold-stimulated WT or CC1-KO hepatocytes were pretreated with or without siRNA against ASK1. (B) Western blot–assisted detection and relative intensity ratio of CC1, ASK1, p-p38. VCL expression served as an internal control and used for normalization (n = 3/group). (C) Representative (n = 3/group) immunohistochemical staining of 4HNE (red, upper panels), HMGB1 (red, middle panels), and dead cell detection (red, lower panels). (D) Quantification of dead cells/HPF (n = 4–5/group). *P < 0.05, 1-way ANOVA followed by Tukey’s HSD test.

Article Snippet: In separate experiments, donor livers were incubated with ASK1-specific small molecule inhibitor (10 μg/15 mL, MSC2032964A, R&D Systems) throughout 18 hours of cold storage.

Techniques: Incubation, Western Blot, Expressing, Immunohistochemical staining, Staining

(A–C) Groups of WT and CC1-KO livers were stored in UW solution (4°C/18 hours) with or without ASK1 inhibitor (10 μg/15 mL). (A) Western blot–assisted detection and relative intensity ratio of CC1 and p-p38. VCL expression served as an internal control and used for normalization (n = 3–4/group). (B) Representative (n = 3/group) immunohistochemical staining of CC1/4HNE and CC1/HMGB1. (C) Liver flush (20 μL) from cold-stressed WT or CC1-KO livers with or without ASK1 inhibitor were analyzed by Western blots for HMGB1 levels (n = 3–4/group). (D–H) Cold-stored (4°C/18 hours) WT or CC1-KO livers were transplanted into recipient mice, and OLT and serum samples were analyzed at 6 hours after reperfusion. Some CC1-KO grafts were preincubated with ASK1 inhibitor (10 μg/15 mL) during cold storage (4°C/18 hours). Separate OLT recipient groups were monitored for 20-day survival. (D) Representative H&E (original magnification ×100) and TUNEL staining. (E) sAST and sALT levels (IU/L; n = 7–8/group). (F) Suzuki’s histological grading of liver IRI (n = 7–8/group). (G) Quantification of TUNEL-positive cells/HPF (n = 7–8/group). Data shown as mean ± SD. *P < 0.05, 1-way ANOVA followed by Tukey’s HSD test. (H) Recipient mice were monitored for 20 days and cumulative survival was analyzed (Kaplan-Meier method). Dotted line: WT → WT; solid line: CC1-KO → WT; bold line: CC1-KO+ASK1 inhibitor → WT (n = 6–9/group; *P < 0.05 vs. CC1-KO → WT, log-rank test).

Journal: The Journal of Clinical Investigation

Article Title: Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury

doi: 10.1172/JCI133142

Figure Lengend Snippet: (A–C) Groups of WT and CC1-KO livers were stored in UW solution (4°C/18 hours) with or without ASK1 inhibitor (10 μg/15 mL). (A) Western blot–assisted detection and relative intensity ratio of CC1 and p-p38. VCL expression served as an internal control and used for normalization (n = 3–4/group). (B) Representative (n = 3/group) immunohistochemical staining of CC1/4HNE and CC1/HMGB1. (C) Liver flush (20 μL) from cold-stressed WT or CC1-KO livers with or without ASK1 inhibitor were analyzed by Western blots for HMGB1 levels (n = 3–4/group). (D–H) Cold-stored (4°C/18 hours) WT or CC1-KO livers were transplanted into recipient mice, and OLT and serum samples were analyzed at 6 hours after reperfusion. Some CC1-KO grafts were preincubated with ASK1 inhibitor (10 μg/15 mL) during cold storage (4°C/18 hours). Separate OLT recipient groups were monitored for 20-day survival. (D) Representative H&E (original magnification ×100) and TUNEL staining. (E) sAST and sALT levels (IU/L; n = 7–8/group). (F) Suzuki’s histological grading of liver IRI (n = 7–8/group). (G) Quantification of TUNEL-positive cells/HPF (n = 7–8/group). Data shown as mean ± SD. *P < 0.05, 1-way ANOVA followed by Tukey’s HSD test. (H) Recipient mice were monitored for 20 days and cumulative survival was analyzed (Kaplan-Meier method). Dotted line: WT → WT; solid line: CC1-KO → WT; bold line: CC1-KO+ASK1 inhibitor → WT (n = 6–9/group; *P < 0.05 vs. CC1-KO → WT, log-rank test).

Article Snippet: In separate experiments, donor livers were incubated with ASK1-specific small molecule inhibitor (10 μg/15 mL, MSC2032964A, R&D Systems) throughout 18 hours of cold storage.

Techniques: Western Blot, Expressing, Immunohistochemical staining, Staining, TUNEL Assay

Pretransplant (after cold storage) human liver Bx (n = 60) were analyzed by Western blots with β-actin normalization for CEACAM1, ASK1, and p-p38 levels (see Supplemental Figure 1A). (A) Bx samples were divided into low (n = 30) and high (n = 30) CEACAM1 expression groups based on the relative CEACAM1/β-actin levels (cutoff = 0.85, median). (B) Western blot–assisted expression of ASK1 and p-p38. Data shown in dot plots and bars indicate mean ± SEM. #P < 0.05 (Mann-Whitney U test). (C) Four representative Western blots are shown (case 1/2: low CEACAM1, case 3/4: high CEACAM1). (D) Representative (n = 3) CEACAM1/4HNE staining (original magnification ×200). (E) Representative (n = 3) CEACAM1/HMGB1 staining (original magnification ×400).

Journal: The Journal of Clinical Investigation

Article Title: Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury

doi: 10.1172/JCI133142

Figure Lengend Snippet: Pretransplant (after cold storage) human liver Bx (n = 60) were analyzed by Western blots with β-actin normalization for CEACAM1, ASK1, and p-p38 levels (see Supplemental Figure 1A). (A) Bx samples were divided into low (n = 30) and high (n = 30) CEACAM1 expression groups based on the relative CEACAM1/β-actin levels (cutoff = 0.85, median). (B) Western blot–assisted expression of ASK1 and p-p38. Data shown in dot plots and bars indicate mean ± SEM. #P < 0.05 (Mann-Whitney U test). (C) Four representative Western blots are shown (case 1/2: low CEACAM1, case 3/4: high CEACAM1). (D) Representative (n = 3) CEACAM1/4HNE staining (original magnification ×200). (E) Representative (n = 3) CEACAM1/HMGB1 staining (original magnification ×400).

Article Snippet: In separate experiments, donor livers were incubated with ASK1-specific small molecule inhibitor (10 μg/15 mL, MSC2032964A, R&D Systems) throughout 18 hours of cold storage.

Techniques: Western Blot, Expressing, MANN-WHITNEY, Staining

The figure shows the timeline of the study. Eight treatment groups of mice were used (total mice, N=120): (1) sham (surgery without ischemia and reperfusion) at 60 min, 24 h, or 7 d (n=4 per each time point); (2) vehicle ischemia and reperfusion (0.1 mL vehicle solution at time of reperfusion) for 60 min, for 24 h for TTC and molecular analysis, or for 7 d (n=6 per each time point); (3) ASK1 inhibitor, GS-459679, single injection at 24 h for TTC (10 mg/kg in 0.1 mL vehicle solution; n=6); (4) GS-459679 single injection (30 mg/kg in 0.1 mL vehicle solution) at 60 min, at 24 h for TTC and molecular analysis, or at 7 d (n=6 per each time point); (5) GS-459679 30 mg/kg or vehicle BID for 7 d (n=6 per treatment arm); (6) delayed administration of GS-459679 30 mg/kg at 5, 15, and 30 min after reperfusion (n=6 per treatment arm); (7) GS-459679 30 mg/kg and vehicle single injection given at reperfusion after 60 min of ischemia (n=6 per treatment arm); and (8) permanent ligation (no reperfusion) treated with GS-459679 30 mg/kg or vehicle solution BID for 7 d (n=6 per treatment arm). TTC indicates triphenyl tetrazolium chloride staining for infarct size; BID, bis in die , from the Latin for twice daily.

Journal: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Article Title: Inhibition of Apoptosis Signal–Regulating Kinase 1 Reduces Myocardial Ischemia–Reperfusion Injury in the Mouse

doi: 10.1161/JAHA.112.002360

Figure Lengend Snippet: The figure shows the timeline of the study. Eight treatment groups of mice were used (total mice, N=120): (1) sham (surgery without ischemia and reperfusion) at 60 min, 24 h, or 7 d (n=4 per each time point); (2) vehicle ischemia and reperfusion (0.1 mL vehicle solution at time of reperfusion) for 60 min, for 24 h for TTC and molecular analysis, or for 7 d (n=6 per each time point); (3) ASK1 inhibitor, GS-459679, single injection at 24 h for TTC (10 mg/kg in 0.1 mL vehicle solution; n=6); (4) GS-459679 single injection (30 mg/kg in 0.1 mL vehicle solution) at 60 min, at 24 h for TTC and molecular analysis, or at 7 d (n=6 per each time point); (5) GS-459679 30 mg/kg or vehicle BID for 7 d (n=6 per treatment arm); (6) delayed administration of GS-459679 30 mg/kg at 5, 15, and 30 min after reperfusion (n=6 per treatment arm); (7) GS-459679 30 mg/kg and vehicle single injection given at reperfusion after 60 min of ischemia (n=6 per treatment arm); and (8) permanent ligation (no reperfusion) treated with GS-459679 30 mg/kg or vehicle solution BID for 7 d (n=6 per treatment arm). TTC indicates triphenyl tetrazolium chloride staining for infarct size; BID, bis in die , from the Latin for twice daily.

Article Snippet: In the present study, we use a small-molecule inhibitor of ASK1 (GS-459679) developed at Gilead Sciences (Foster City, CA) to prevent reperfusion-induced ASK1 activation and to reduce infarct size in a mouse model of AMI due to ischemia–reperfusion.

Techniques: Injection, Ligation, Staining

Administration of the ASK1 inhibitor GS-459679, given at reperfusion after 30 min of myocardial ischemia, inhibited caspase-3 in the heart tissue measured 60 min after reperfusion (top, * P <0.001 vs sham; # P <0.01 vs vehicle) and reduced apoptotic cardiomyocytes measured as TUNEL in the area bordering the infarcted myocardium 24 h after reperfusion (bottom, * P <0.001 vs sham; # P <0.05 vs vehicle). n=4 to 6 per group. AMI indicates acute myocardial infarction.

Journal: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Article Title: Inhibition of Apoptosis Signal–Regulating Kinase 1 Reduces Myocardial Ischemia–Reperfusion Injury in the Mouse

doi: 10.1161/JAHA.112.002360

Figure Lengend Snippet: Administration of the ASK1 inhibitor GS-459679, given at reperfusion after 30 min of myocardial ischemia, inhibited caspase-3 in the heart tissue measured 60 min after reperfusion (top, * P <0.001 vs sham; # P <0.01 vs vehicle) and reduced apoptotic cardiomyocytes measured as TUNEL in the area bordering the infarcted myocardium 24 h after reperfusion (bottom, * P <0.001 vs sham; # P <0.05 vs vehicle). n=4 to 6 per group. AMI indicates acute myocardial infarction.

Techniques: TUNEL Assay

$Representative images of Evans blue/triphenyl tetrazolium chloride staining of the hearts are shown in the top panels: Blue marks the nonrisk area of the heart, and the remaining is the risk area, which appears red if viable and white if infarcted. Administration of the ASK1 inhibitor GS-459679 at reperfusion led to a dose-dependent reduction in infarct size (middle panels) and preservation of contractile function (bottom panels). * P <0.001 vs sham; † P <0.001 vs vehicle-treated AMI; ‡ P <0.001 vs 10 mg/kg, n=4 to 6 per group. AMI indicates acute myocardial infarction; LV, left ventricle; WMSI, wall motion score index; and LVEF, left ventricular ejection fraction.$

Journal: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Article Title: Inhibition of Apoptosis Signal–Regulating Kinase 1 Reduces Myocardial Ischemia–Reperfusion Injury in the Mouse

doi: 10.1161/JAHA.112.002360

Figure Lengend Snippet: Representative images of Evans blue/triphenyl tetrazolium chloride staining of the hearts are shown in the top panels: Blue marks the nonrisk area of the heart, and the remaining is the risk area, which appears red if viable and white if infarcted. Administration of the ASK1 inhibitor GS-459679 at reperfusion led to a dose-dependent reduction in infarct size (middle panels) and preservation of contractile function (bottom panels). * P <0.001 vs sham; † P <0.001 vs vehicle-treated AMI; ‡ P <0.001 vs 10 mg/kg, n=4 to 6 per group. AMI indicates acute myocardial infarction; LV, left ventricle; WMSI, wall motion score index; and LVEF, left ventricular ejection fraction.

Techniques: Staining, Preserving

$Representative images of heart sections stained with Masson's trichrome are shown: The fibrotic scar appears blue, and the viable myocardium is red. Administration of the ASK1 inhibitor (GS-459679, 30 mg/kg) at reperfusion led to a reduction in infarct scar size measured at 7 d (top panels) and preservation of contractile function (bottom panels). The administration of multiple daily doses compared with a single dose at reperfusion yielded no additional benefit. * P <0.001 vs sham; † P <0.001 vs vehicle-treated AMI; n=4 to 6 per group. AMI indicates acute myocardial infarction; LV, left ventricle; WMSI, wall motion score index; and LVEF, left ventricular ejection fraction.$

Journal: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Article Title: Inhibition of Apoptosis Signal–Regulating Kinase 1 Reduces Myocardial Ischemia–Reperfusion Injury in the Mouse

doi: 10.1161/JAHA.112.002360

Figure Lengend Snippet: Representative images of heart sections stained with Masson's trichrome are shown: The fibrotic scar appears blue, and the viable myocardium is red. Administration of the ASK1 inhibitor (GS-459679, 30 mg/kg) at reperfusion led to a reduction in infarct scar size measured at 7 d (top panels) and preservation of contractile function (bottom panels). The administration of multiple daily doses compared with a single dose at reperfusion yielded no additional benefit. * P <0.001 vs sham; † P <0.001 vs vehicle-treated AMI; n=4 to 6 per group. AMI indicates acute myocardial infarction; LV, left ventricle; WMSI, wall motion score index; and LVEF, left ventricular ejection fraction.

Techniques: Staining, Preserving

$Administration of the ASK1 inhibitor (GS-459679, 30 mg/kg) with a delay at reperfusion led to a time-dependent loss of effect on infarct size (top panels) and regional wall motion abnormalities (bottom left panel), whereas global LV systolic function also was preserved with a 30-min delay (bottom right panel). * P <0.001 vs sham; † P <0.001 vs vehicle-treated AMI; ‡ P <0.001 vs no delay. n=4 to 6 per group. AMI indicates acute myocardial infarction; LV, left ventricle; WMSI, wall motion score index; and LVEF, left ventricular ejection fraction.$

Journal: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Article Title: Inhibition of Apoptosis Signal–Regulating Kinase 1 Reduces Myocardial Ischemia–Reperfusion Injury in the Mouse

doi: 10.1161/JAHA.112.002360

Figure Lengend Snippet: Administration of the ASK1 inhibitor (GS-459679, 30 mg/kg) with a delay at reperfusion led to a time-dependent loss of effect on infarct size (top panels) and regional wall motion abnormalities (bottom left panel), whereas global LV systolic function also was preserved with a 30-min delay (bottom right panel). * P <0.001 vs sham; † P <0.001 vs vehicle-treated AMI; ‡ P <0.001 vs no delay. n=4 to 6 per group. AMI indicates acute myocardial infarction; LV, left ventricle; WMSI, wall motion score index; and LVEF, left ventricular ejection fraction.

Techniques:

$Administration of the ASK1 inhibitor (GS-459679, 30 mg/kg) after the onset of ischemia in a model of AMI without reperfusion did not affect infarct size (top panels) or regional/global systolic function (bottom panels). * P <0.001 vs sham. n=4 to 8 per group. AMI indicates acute myocardial infarction; LV, left ventricle; WMSI, wall motion score index; and LVEF, left ventricular ejection fraction.$

Journal: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Article Title: Inhibition of Apoptosis Signal–Regulating Kinase 1 Reduces Myocardial Ischemia–Reperfusion Injury in the Mouse

doi: 10.1161/JAHA.112.002360

Figure Lengend Snippet: Administration of the ASK1 inhibitor (GS-459679, 30 mg/kg) after the onset of ischemia in a model of AMI without reperfusion did not affect infarct size (top panels) or regional/global systolic function (bottom panels). * P <0.001 vs sham. n=4 to 8 per group. AMI indicates acute myocardial infarction; LV, left ventricle; WMSI, wall motion score index; and LVEF, left ventricular ejection fraction.

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