Chk
Signaling Pathway Map
Research Area
Inhibitory Selectivity
Isoform-specific Inhibitors
Chk Products
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1532 |
AZD7762AZD7762 is a potent and selective inhibitor of Chk1 with IC50 of 5 nM in a cell-free assay. It is equally potent against Chk2 and less potent against CAM, Yes, Fyn, Lyn, Hck and Lck. Phase 1. |
E, CAL120 cells were either untreated or pretreated with gemcitabine for 24 hours followed by treatment with AZD7762 and /or MK-1775 for an additional 2 hours (top) or 8 hours (bottom), before lysis. Western blot analysis of Cyclin B1, CDK1 (phospho-Y15 and total) expression, and β-tubulin as loading control. F, induction of the intra–S-phase checkpoint was not affected by WEE1 inhibition. CAL120 cells were pulse-labeled with 10 μmol/L BrdU for 30 minutes, washed (W), and then treated with 1 μmol/L camptothecin (CPT) for 30 minutes. After CPT removal (0 hours), BrdU-labeled S-phase cells (BrdU+ , indicated by boxed area) were monitored at the indicated time points in the absence (iii) or presence of MK-1775 (iv) or AZD7762 as a positive control (v). Control cells (ctr) were not exposed to CPT and cultured in the absence (i) or presence of MK-1775 (ii). Arrowheads indicate delayed S-phase progression. |
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| S2626 |
Rabusertib (LY2603618)Rabusertib (LY2603618) is a highly selective Chk1 inhibitor with potential anti-tumor activity in a cell-free assay. IC50=7 nM, showing approximately 100-fold more potent against Chk1 than against any of the other protein kinases evaluated. Rabusertib (LY2603618) induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Rabusertib (LY2603618) induces bak-dependent apoptosis in AML cell lines. |
MK-1775 and LY2603618 synergize to induce apoptosis in AML cell lines and primary patient samples. U937 and CTS cells were treated for 8 h. Whole cell lysates were subjected to Western blotting and probed with anti-γH2AX, -pCHK1, -p-cdc25c, -p-CDK1, -p-CDK2, -CDK1, or -β-actin antibody. Densitometry measurements, as described in the Materials and methods section, are shown below the corresponding Western blot.
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| S2735 |
MK-8776 (SCH 900776)MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2. |
Hela cell was trypsinized and plated at 30% confluence in DMEM. 16 hours later, MK-8776 (SCH900776) was added at final concentrations of 0, 5, 10 and 25uM. Another 24 hours later, cells were harvested in RIPA with protease and phosphatase inhibitor cocktail. Total protein concentration was measured by BCA method. Lysates equivalent to 20ug total protein were subject to Western Blot, using total- CHK1, pS345-CHK1 and beta-actin (internal control) antibodies. |
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| S2683 |
CHIR-124CHIR-124 is a novel and potent Chk1 inhibitor with IC50 of 0.3 nM in a cell-free assay. It shows 2,000-fold selectivity against Chk2, 500- to 5,000-fold less activity against CDK2/4 and Cdc2. |
Cell proliferation of IGR-CaP1-R100 cells. Cells were treated with 100nM CHIR-124 in the presence or absence of 100nM Docetaxel or with Docetaxel alone during 4 days. Proliferation was assessed using WST1. |
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| S2904 |
PF-477736PF-477736 is a selective, potent and ATP-competitive Chk1 inhibitor with Ki of 0.49 nM in a cell-free assay and also inhibits VEGFR2, Aurora-A, FGFR3, Flt3, Fms (CSF1R), Ret and Yes. It shows ~100-fold selectivity for Chk1 than Chk2. Phase 1. |
Cells were treated at the same concentrations as in Caspase3/7 assay for 16 hours and total cell lysates were prepared for Western blotting. GAPDH was used as a loading control.
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| S9639New |
VX-803 (M4344)VX-803 (M4344) is an ATP-competitive, orally active, and selective inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase with Ki of < 150 pM. VX-803 (M4344) potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with IC50 of 8 nM. VX-803 (M4344) exhibits potential antineoplastic activity. |
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| S8526 |
GDC-0575 (ARRY-575)GDC-0575 (ARRY-575, RG7741) is a potent and selective CHK1 inhibitor with an IC50 of 1.2 nM. |
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| S7740 |
SAR-020106SAR-020106 is an ATP-competitive, potent, and selective CHK1 inhibitor with an IC50 of 13.3 nM. |
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| S8253 |
CCT245737CCT245737 is an orally active CHK1 inhibitor with The IC50 of 1.4 nM. It exhibits >1,000-fold selectivity against CHK2 and CDK1. |
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| S8148 |
PD0166285PD0166285 is a potent Wee1 and Chk1 inhibitor with activity at nanomolar concentrations (IC50=24 nM for Wee1 and 72 nM for Myt1). PD0166285 is also a novel G2 checkpoint abrogator. PD0166285 induces apoptosis. |
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| S8632 |
Chk2 Inhibitor II (BML-277)Chk2 Inhibitor II (BML-277) is an ATP-competitive inhibitor of Chk2 with IC50 of 15 nM. It is 1000-fold more selective toward Chk2 serine/threonine kinase than for Chk1 and Cdk1/B kinases. Chk2 Inhibitor II (BML-277) dose dependently protects human CD4(+) and CD8(+) T-cells from apoptosis due to ionizing radiation. |
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| S7178 |
Prexasertib HCl (LY2606368)Prexasertib (LY2606368) is an ATP-competitive CHK1 inhibitor with a Ki value of 0.9 nmol/L. For CHK2 and RSK, its IC50 values are 8 nM and 9 nM respectively in cell-free assay. |
EW8 and TC71 cells were treated with increasing doses of prexasertib for 6 hours. Cell lysates were then collected and blotted for p-CHK1-345.
|
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1532 |
AZD7762AZD7762 is a potent and selective inhibitor of Chk1 with IC50 of 5 nM in a cell-free assay. It is equally potent against Chk2 and less potent against CAM, Yes, Fyn, Lyn, Hck and Lck. Phase 1. |
E, CAL120 cells were either untreated or pretreated with gemcitabine for 24 hours followed by treatment with AZD7762 and /or MK-1775 for an additional 2 hours (top) or 8 hours (bottom), before lysis. Western blot analysis of Cyclin B1, CDK1 (phospho-Y15 and total) expression, and β-tubulin as loading control. F, induction of the intra–S-phase checkpoint was not affected by WEE1 inhibition. CAL120 cells were pulse-labeled with 10 μmol/L BrdU for 30 minutes, washed (W), and then treated with 1 μmol/L camptothecin (CPT) for 30 minutes. After CPT removal (0 hours), BrdU-labeled S-phase cells (BrdU+ , indicated by boxed area) were monitored at the indicated time points in the absence (iii) or presence of MK-1775 (iv) or AZD7762 as a positive control (v). Control cells (ctr) were not exposed to CPT and cultured in the absence (i) or presence of MK-1775 (ii). Arrowheads indicate delayed S-phase progression. |
|
| S2626 |
Rabusertib (LY2603618)Rabusertib (LY2603618) is a highly selective Chk1 inhibitor with potential anti-tumor activity in a cell-free assay. IC50=7 nM, showing approximately 100-fold more potent against Chk1 than against any of the other protein kinases evaluated. Rabusertib (LY2603618) induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Rabusertib (LY2603618) induces bak-dependent apoptosis in AML cell lines. |
MK-1775 and LY2603618 synergize to induce apoptosis in AML cell lines and primary patient samples. U937 and CTS cells were treated for 8 h. Whole cell lysates were subjected to Western blotting and probed with anti-γH2AX, -pCHK1, -p-cdc25c, -p-CDK1, -p-CDK2, -CDK1, or -β-actin antibody. Densitometry measurements, as described in the Materials and methods section, are shown below the corresponding Western blot.
|
|
| S2735 |
MK-8776 (SCH 900776)MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2. |
Hela cell was trypsinized and plated at 30% confluence in DMEM. 16 hours later, MK-8776 (SCH900776) was added at final concentrations of 0, 5, 10 and 25uM. Another 24 hours later, cells were harvested in RIPA with protease and phosphatase inhibitor cocktail. Total protein concentration was measured by BCA method. Lysates equivalent to 20ug total protein were subject to Western Blot, using total- CHK1, pS345-CHK1 and beta-actin (internal control) antibodies. |
|
| S2683 |
CHIR-124CHIR-124 is a novel and potent Chk1 inhibitor with IC50 of 0.3 nM in a cell-free assay. It shows 2,000-fold selectivity against Chk2, 500- to 5,000-fold less activity against CDK2/4 and Cdc2. |
Cell proliferation of IGR-CaP1-R100 cells. Cells were treated with 100nM CHIR-124 in the presence or absence of 100nM Docetaxel or with Docetaxel alone during 4 days. Proliferation was assessed using WST1. |
|
| S2904 |
PF-477736PF-477736 is a selective, potent and ATP-competitive Chk1 inhibitor with Ki of 0.49 nM in a cell-free assay and also inhibits VEGFR2, Aurora-A, FGFR3, Flt3, Fms (CSF1R), Ret and Yes. It shows ~100-fold selectivity for Chk1 than Chk2. Phase 1. |
Cells were treated at the same concentrations as in Caspase3/7 assay for 16 hours and total cell lysates were prepared for Western blotting. GAPDH was used as a loading control.
|
|
| S9639New |
VX-803 (M4344)VX-803 (M4344) is an ATP-competitive, orally active, and selective inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase with Ki of < 150 pM. VX-803 (M4344) potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with IC50 of 8 nM. VX-803 (M4344) exhibits potential antineoplastic activity. |
||
| S8526 |
GDC-0575 (ARRY-575)GDC-0575 (ARRY-575, RG7741) is a potent and selective CHK1 inhibitor with an IC50 of 1.2 nM. |
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| S7740 |
SAR-020106SAR-020106 is an ATP-competitive, potent, and selective CHK1 inhibitor with an IC50 of 13.3 nM. |
||
| S8253 |
CCT245737CCT245737 is an orally active CHK1 inhibitor with The IC50 of 1.4 nM. It exhibits >1,000-fold selectivity against CHK2 and CDK1. |
||
| S8148 |
PD0166285PD0166285 is a potent Wee1 and Chk1 inhibitor with activity at nanomolar concentrations (IC50=24 nM for Wee1 and 72 nM for Myt1). PD0166285 is also a novel G2 checkpoint abrogator. PD0166285 induces apoptosis. |
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| S8632 |
Chk2 Inhibitor II (BML-277)Chk2 Inhibitor II (BML-277) is an ATP-competitive inhibitor of Chk2 with IC50 of 15 nM. It is 1000-fold more selective toward Chk2 serine/threonine kinase than for Chk1 and Cdk1/B kinases. Chk2 Inhibitor II (BML-277) dose dependently protects human CD4(+) and CD8(+) T-cells from apoptosis due to ionizing radiation. |
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| S7178 |
Prexasertib HCl (LY2606368)Prexasertib (LY2606368) is an ATP-competitive CHK1 inhibitor with a Ki value of 0.9 nmol/L. For CHK2 and RSK, its IC50 values are 8 nM and 9 nM respectively in cell-free assay. |
EW8 and TC71 cells were treated with increasing doses of prexasertib for 6 hours. Cell lysates were then collected and blotted for p-CHK1-345.
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