E0404New |
Zapnometinib (PD0184264)
|
Zapnometinib (PD0184264, ATR-002), an major active metabolite of CI-1040, is a novel MEK inhibitor with an IC50 of 5.7 nM. |
|
|
S1008 |
Selumetinib (AZD6244)
|
Selumetinib (AZD6244, ARRY-142886) is a potent, highly selective MEK inhibitor with IC50 of 14 nM for MEK1 and Kd value of 530 nM for MEK2. It also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Selumetinib suppresses cell proliferation, migration and trigger apoptosis. Phase 3. |
-
Cancer Cell, 2022, S1535-6108(21)00662-0
-
Nat Commun, 2022, 13(1):1691
-
Bone Res, 2022, 10(1):27
|
|
S1020 |
PD184352 (CI-1040)
|
PD184352 (CI-1040) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM in cell-based assays, 100-fold more selective for MEK1/2 than MEK5. PD184352 (CI-1040) selectively induces apoptosis. Phase 2. |
-
Cancer Cell, 2022, S1535-6108(22)00005-8
-
Signal Transduct Target Ther, 2022, 7(1):51
-
Proc Natl Acad Sci U S A, 2022, 119(3)e2114134119
|
|
S1036 |
Mirdametinib (PD0325901)
|
Mirdametinib (PD0325901) is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM in cell-free assays, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 2. |
-
Nature, 2022, 604(7904):111-119
-
Cell Stem Cell, 2022, S1934-5909(22)00010-8
-
Mol Cell, 2022, 82(6):1169-1185.e7
|
|
S1066 |
SL-327
|
SL327 is a selective inhibitor for MEK1/2 with IC50 of 0.18 μM/ 0.22 μM, no activity towards Erk1, MKK3, MKK4, c-JUN, PKC, PKA, or CamKII;capable of transport through the blood-brain barrier. |
-
Eur J Neurosci, 2022, 55(6):1471-1482
-
Nat Commun, 2020, 25;11(1):1556
-
Neuroscience, 2020, 430:1-11
|
|
S1089 |
Refametinib (RDEA119)
|
Refametinib (RDEA119, Bay 86-9766) is a potent, ATP non-competitive and highly selective inhibitor of MEK1 and MEK2 with IC50 of 19 nM and 47 nM, respectively. |
-
Genome Med, 2021, 13(1):116
-
Mol Oncol, 2021, 10.1002/1878-0261.13153
-
Int J Mol Sci, 2021, 22(13)6727
|
|
S1102 |
U0126-EtOH
|
U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM in cell-free assays, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD98059. U0126 inhibits autophagy and mitophagy with antiviral activity. |
-
Adv Sci (Weinh), 2022, 10.1002/advs.202104055
-
Cell Rep, 2022, 38(11):110522
-
Elife, 2022, 11e76183
|
|
S1177 |
PD98059
|
PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM in a cell-free assay, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2. PD98059 is a ligand for the aryl hydrocarbon receptor (AHR) and functions as an AHR antagonist. |
-
Cancer Lett, 2022, 541:215749
-
Neuropathol Appl Neurobiol, 2022, e12795
-
Front Pharmacol, 2022, 13:817596
|
|
S1392 |
Pelitinib (EKB-569)
|
Pelitinib (EKB-569) is a potent irreversible EGFR inhibitor with IC50 of 38.5 nM. Pelitinib (EKB-569) also slightly inhibits Src, MEK/ERK and ErbB2 with IC50s of 282 nM, 800 nM and 1255 nM, respectively. Phase2. |
-
Sci Rep, 2022, 12(1):2928
-
Mol Cancer Ther, 2020, 5;molcanther.1131.2019
-
Nat Cell Biol, 2019, 21(6):778-790
|
|
S1475 |
Pimasertib (AS-703026)
|
Pimasertib (AS-703026, MSC1936369B, SAR 245509) is a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2 with IC50 of 5 nM-2 μM in MM cell lines. Phase 2. |
-
Cancers (Basel), 2022, 14(6)1575
-
Front Oncol, 2021, 11:780654
-
Mol Oncol, 2021, 10.1002/1878-0261.13153
|
|
S1530 |
BIX 02188
|
BIX02188 is a selective inhibitor of MEK5 with IC50 of 4.3 nM, also inhibits ERK5 catalytic activity with IC50 of 810 nM, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2. |
-
Cell Stem Cell, 2021, 28(2):257-272.e11
-
Front Cell Dev Biol, 2021, 9:742049
-
Nat Immunol, 2018, 19(3):233-245
|
|
S1531 |
BIX 02189
|
BIX02189 is a selective inhibitor of MEK5 with IC50 of 1.5 nM, also inhibits ERK5 catalytic activity with IC50 of 59 nM in cell-free assays, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2. |
-
Cells, 2022, 11(9)1392
-
Cell Stem Cell, 2021, 28(2):257-272.e11
-
Front Cell Dev Biol, 2021, 9:742049
|
|
S1568 |
PD318088
|
PD318088 is a non-ATP competitive allosteric MEK1/2 inhibitor, binds simultaneously with ATP in a region of the MEK1 active site that is adjacent to the ATP-binding site. |
-
Cancers (Basel), 2022, 14(6)1575
-
Curr Protoc, 2021, 1(6):e180
-
Nature, 2019, 569(7757):509-513
|
|
S2134 |
AZD8330
|
AZD8330 (ARRY704) is a novel, selective, non-ATP competitive MEK 1/2 inhibitor with IC50 of 7 nM. Phase 1. |
-
Cancers (Basel), 2022, 14(6)1575
-
Curr Protoc, 2021, 1(6):e180
-
Int J Clin Oncol, 2020, 19
|
|
S2310 |
Honokiol (NSC 293100)
|
Honokiol (NSC 293100) is the active principle of magnolia extract that inhibits Akt-phosphorylation and promotes ERK1/2 phosphorylation. Honokiol causes G0/G1 phase arrest, induces apoptosis, and autophagy via the ROS/ERK1/2 signaling pathway. Honokiol inhibits hepatitis C virus (HCV) infection. Phase 3. |
-
Br J Pharmacol, 2022, 10.1111/bph.15837
-
Cell Death Dis, 2021, 12(9):847
-
Front Cell Dev Biol, 2021, 9:619475
|
|
S2326 |
Myricetin
|
Myricetin, a natural flavonoid with antioxidant and anti tumor properties, is a novel inhibitor of MEK1 activity and transformation of JB6 P+ mouse epidermal cells. It also inhibits PI3Kγ with Kd of 0.17 μM. |
-
Evid Based Complement Alternat Med, 2022, 2022:3115312
-
Molecules, 2021, 26(5)1210
-
Front Med (Lausanne), 2020, 7:71
|
|
S2617 |
TAK-733
|
TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc. Phase 1. |
-
Cancers (Basel), 2022, 14(6)1575
-
Cells, 2022, 11(5)775
-
Curr Protoc, 2021, 1(6):e180
|
|
S2673 |
Trametinib (GSK1120212)
|
Trametinib (GSK1120212, JTP-74057, Mekinist) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2. Trametinib activates autophagy and induces apoptosis. |
-
Nature, 2022, 603(7900):335-342
-
Cell, 2022, S0092-8674(22)00472-X
-
Cancer Cell, 2022, S1535-6108(21)00662-0
|
|
S4484 |
Trametinib DMSO solvate
|
Trametinib (GSK1120212, JTP-74057, Mekinist) DMSO solvate is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assay. Trametinib activates autophagy and induces apoptosis. |
-
Cell Rep, 2022, 38(7):110374
|
|
S7007 |
Binimetinib (MEK162)
|
Binimetinib (MEK162, ARRY-162, ARRY-438162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM in a cell-free assay. Binimetinib induces G1 cell cycle arrest and apoptosis in human NSCLC cell lines and induces autophagy. Phase 3. |
-
Cell, 2022, S0092-8674(22)00472-X
-
EMBO Mol Med, 2022, e14876
-
Cancer Res, 2022, canres.1397.2021
|
|
S7170 |
RO5126766 (CH5126766)
|
RO5126766 (CH5126766, VS 6766, CKI-27, R-7304, RG-7304) is a dual RAF/MEK inhibitor with IC50 of 8.2 nM,19 nM, 56 nM, and 160 nM for BRAF V600E, BRAF, CRAF, and MEK1, respectively. Phase 1.
|
-
EMBO Mol Med, 2021, e11814
-
Cancer Sci, 2021, 112(10):4026-4036
-
Nature, 2020, 588(7838):509-514
|
|
S7553 |
GDC-0623
|
GDC-0623 (G-868) is a potent and ATP-uncompetitive MEK1 inhibitor with Ki of 0.13 nM. Phase 1.
|
-
Int J Endocrinol, 2021, 2021:5720145
-
Curr Protoc, 2021, 1(6):e180
-
Nature, 2019, 569(7757):509-513
|
|
S7843 |
BI-847325
|
BI-847325 is an orally bioavailable, and selective dual MEK/Aurora kinase inhibitor with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM for Xenopus laevis Aurora B, human Aurora A and Aurora C, as well as human MEK1 and MEK2, respectively. Phase 1. |
-
Sci Rep, 2021, 11(1):9161
-
Curr Protoc, 2021, 1(6):e180
-
Nature, 2019, 569(7757):509-513
|
|
S8041 |
Cobimetinib (GDC-0973)
|
Cobimetinib (GDC-0973, RG7420) is a potent and highly selective MEK1 inhibitor with IC50 of 4.2 nM, showing more than 100-fold selectively for MEK1 over MEK2 and showed no significant inhibition when tested against a panel of more than 100 of serine-threonine and tyrosine kinases. Cobimetinib induces apoptosis. Phase 3. |
-
Cancer Cell, 2022, S1535-6108(21)00662-0
-
Signal Transduct Target Ther, 2022, 7(1):51
-
Nat Commun, 2022, 13(1):1100
|
|
S8355 |
APS-2-79 HCl
|
APS-2-79 is a MAPK antagonist that modulating KSR-dependent MAPK signalling by antagonizing RAF heterodimerization as well as the conformational changes required for phosphorylation and activation of KSR-bound MEK. IC50=120 ± 23 nM. |
-
Sci Adv, 2019, 5(11):eaax4249
-
Exp Ther Med, 2018, 15(6):5269-5274
|
|
E0404New |
Zapnometinib (PD0184264)
|
Zapnometinib (PD0184264, ATR-002), an major active metabolite of CI-1040, is a novel MEK inhibitor with an IC50 of 5.7 nM. |
|
|
S1008 |
Selumetinib (AZD6244)
|
Selumetinib (AZD6244, ARRY-142886) is a potent, highly selective MEK inhibitor with IC50 of 14 nM for MEK1 and Kd value of 530 nM for MEK2. It also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Selumetinib suppresses cell proliferation, migration and trigger apoptosis. Phase 3. |
- Cancer Cell, 2022, S1535-6108(21)00662-0
- Nat Commun, 2022, 13(1):1691
- Bone Res, 2022, 10(1):27
|
|
S1020 |
PD184352 (CI-1040)
|
PD184352 (CI-1040) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM in cell-based assays, 100-fold more selective for MEK1/2 than MEK5. PD184352 (CI-1040) selectively induces apoptosis. Phase 2. |
- Cancer Cell, 2022, S1535-6108(22)00005-8
- Signal Transduct Target Ther, 2022, 7(1):51
- Proc Natl Acad Sci U S A, 2022, 119(3)e2114134119
|
|
S1036 |
Mirdametinib (PD0325901)
|
Mirdametinib (PD0325901) is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM in cell-free assays, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 2. |
- Nature, 2022, 604(7904):111-119
- Cell Stem Cell, 2022, S1934-5909(22)00010-8
- Mol Cell, 2022, 82(6):1169-1185.e7
|
|
S1066 |
SL-327
|
SL327 is a selective inhibitor for MEK1/2 with IC50 of 0.18 μM/ 0.22 μM, no activity towards Erk1, MKK3, MKK4, c-JUN, PKC, PKA, or CamKII;capable of transport through the blood-brain barrier. |
- Eur J Neurosci, 2022, 55(6):1471-1482
- Nat Commun, 2020, 25;11(1):1556
- Neuroscience, 2020, 430:1-11
|
|
S1089 |
Refametinib (RDEA119)
|
Refametinib (RDEA119, Bay 86-9766) is a potent, ATP non-competitive and highly selective inhibitor of MEK1 and MEK2 with IC50 of 19 nM and 47 nM, respectively. |
- Genome Med, 2021, 13(1):116
- Mol Oncol, 2021, 10.1002/1878-0261.13153
- Int J Mol Sci, 2021, 22(13)6727
|
|
S1102 |
U0126-EtOH
|
U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM in cell-free assays, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD98059. U0126 inhibits autophagy and mitophagy with antiviral activity. |
- Adv Sci (Weinh), 2022, 10.1002/advs.202104055
- Cell Rep, 2022, 38(11):110522
- Elife, 2022, 11e76183
|
|
S1177 |
PD98059
|
PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM in a cell-free assay, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2. PD98059 is a ligand for the aryl hydrocarbon receptor (AHR) and functions as an AHR antagonist. |
- Cancer Lett, 2022, 541:215749
- Neuropathol Appl Neurobiol, 2022, e12795
- Front Pharmacol, 2022, 13:817596
|
|
S1392 |
Pelitinib (EKB-569)
|
Pelitinib (EKB-569) is a potent irreversible EGFR inhibitor with IC50 of 38.5 nM. Pelitinib (EKB-569) also slightly inhibits Src, MEK/ERK and ErbB2 with IC50s of 282 nM, 800 nM and 1255 nM, respectively. Phase2. |
- Sci Rep, 2022, 12(1):2928
- Mol Cancer Ther, 2020, 5;molcanther.1131.2019
- Nat Cell Biol, 2019, 21(6):778-790
|
|
S1475 |
Pimasertib (AS-703026)
|
Pimasertib (AS-703026, MSC1936369B, SAR 245509) is a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2 with IC50 of 5 nM-2 μM in MM cell lines. Phase 2. |
- Cancers (Basel), 2022, 14(6)1575
- Front Oncol, 2021, 11:780654
- Mol Oncol, 2021, 10.1002/1878-0261.13153
|
|
S1530 |
BIX 02188
|
BIX02188 is a selective inhibitor of MEK5 with IC50 of 4.3 nM, also inhibits ERK5 catalytic activity with IC50 of 810 nM, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2. |
- Cell Stem Cell, 2021, 28(2):257-272.e11
- Front Cell Dev Biol, 2021, 9:742049
- Nat Immunol, 2018, 19(3):233-245
|
|
S1531 |
BIX 02189
|
BIX02189 is a selective inhibitor of MEK5 with IC50 of 1.5 nM, also inhibits ERK5 catalytic activity with IC50 of 59 nM in cell-free assays, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2. |
- Cells, 2022, 11(9)1392
- Cell Stem Cell, 2021, 28(2):257-272.e11
- Front Cell Dev Biol, 2021, 9:742049
|
|
S1568 |
PD318088
|
PD318088 is a non-ATP competitive allosteric MEK1/2 inhibitor, binds simultaneously with ATP in a region of the MEK1 active site that is adjacent to the ATP-binding site. |
- Cancers (Basel), 2022, 14(6)1575
- Curr Protoc, 2021, 1(6):e180
- Nature, 2019, 569(7757):509-513
|
|
S2134 |
AZD8330
|
AZD8330 (ARRY704) is a novel, selective, non-ATP competitive MEK 1/2 inhibitor with IC50 of 7 nM. Phase 1. |
- Cancers (Basel), 2022, 14(6)1575
- Curr Protoc, 2021, 1(6):e180
- Int J Clin Oncol, 2020, 19
|
|
S2310 |
Honokiol (NSC 293100)
|
Honokiol (NSC 293100) is the active principle of magnolia extract that inhibits Akt-phosphorylation and promotes ERK1/2 phosphorylation. Honokiol causes G0/G1 phase arrest, induces apoptosis, and autophagy via the ROS/ERK1/2 signaling pathway. Honokiol inhibits hepatitis C virus (HCV) infection. Phase 3. |
- Br J Pharmacol, 2022, 10.1111/bph.15837
- Cell Death Dis, 2021, 12(9):847
- Front Cell Dev Biol, 2021, 9:619475
|
|
S2326 |
Myricetin
|
Myricetin, a natural flavonoid with antioxidant and anti tumor properties, is a novel inhibitor of MEK1 activity and transformation of JB6 P+ mouse epidermal cells. It also inhibits PI3Kγ with Kd of 0.17 μM. |
- Evid Based Complement Alternat Med, 2022, 2022:3115312
- Molecules, 2021, 26(5)1210
- Front Med (Lausanne), 2020, 7:71
|
|
S2617 |
TAK-733
|
TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc. Phase 1. |
- Cancers (Basel), 2022, 14(6)1575
- Cells, 2022, 11(5)775
- Curr Protoc, 2021, 1(6):e180
|
|
S2673 |
Trametinib (GSK1120212)
|
Trametinib (GSK1120212, JTP-74057, Mekinist) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2. Trametinib activates autophagy and induces apoptosis. |
- Nature, 2022, 603(7900):335-342
- Cell, 2022, S0092-8674(22)00472-X
- Cancer Cell, 2022, S1535-6108(21)00662-0
|
|
S4484 |
Trametinib DMSO solvate
|
Trametinib (GSK1120212, JTP-74057, Mekinist) DMSO solvate is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assay. Trametinib activates autophagy and induces apoptosis. |
- Cell Rep, 2022, 38(7):110374
|
|
S7007 |
Binimetinib (MEK162)
|
Binimetinib (MEK162, ARRY-162, ARRY-438162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM in a cell-free assay. Binimetinib induces G1 cell cycle arrest and apoptosis in human NSCLC cell lines and induces autophagy. Phase 3. |
- Cell, 2022, S0092-8674(22)00472-X
- EMBO Mol Med, 2022, e14876
- Cancer Res, 2022, canres.1397.2021
|
|
S7170 |
RO5126766 (CH5126766)
|
RO5126766 (CH5126766, VS 6766, CKI-27, R-7304, RG-7304) is a dual RAF/MEK inhibitor with IC50 of 8.2 nM,19 nM, 56 nM, and 160 nM for BRAF V600E, BRAF, CRAF, and MEK1, respectively. Phase 1.
|
- EMBO Mol Med, 2021, e11814
- Cancer Sci, 2021, 112(10):4026-4036
- Nature, 2020, 588(7838):509-514
|
|
S7553 |
GDC-0623
|
GDC-0623 (G-868) is a potent and ATP-uncompetitive MEK1 inhibitor with Ki of 0.13 nM. Phase 1.
|
- Int J Endocrinol, 2021, 2021:5720145
- Curr Protoc, 2021, 1(6):e180
- Nature, 2019, 569(7757):509-513
|
|
S7843 |
BI-847325
|
BI-847325 is an orally bioavailable, and selective dual MEK/Aurora kinase inhibitor with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM for Xenopus laevis Aurora B, human Aurora A and Aurora C, as well as human MEK1 and MEK2, respectively. Phase 1. |
- Sci Rep, 2021, 11(1):9161
- Curr Protoc, 2021, 1(6):e180
- Nature, 2019, 569(7757):509-513
|
|
S8041 |
Cobimetinib (GDC-0973)
|
Cobimetinib (GDC-0973, RG7420) is a potent and highly selective MEK1 inhibitor with IC50 of 4.2 nM, showing more than 100-fold selectively for MEK1 over MEK2 and showed no significant inhibition when tested against a panel of more than 100 of serine-threonine and tyrosine kinases. Cobimetinib induces apoptosis. Phase 3. |
- Cancer Cell, 2022, S1535-6108(21)00662-0
- Signal Transduct Target Ther, 2022, 7(1):51
- Nat Commun, 2022, 13(1):1100
|
|