p38 MAPK

Signaling Pathway Map

Research Area

Inhibitory Selectivity

Isoform-specific Inhibitors

p38 MAPK Products

All (22) p38 MAPK Inhibitors (20) p38 MAPK Activators (1) p38 MAPK Modulators (1) New p38 MAPK Products

Catalog No.	Information	Product Use Citations	Product Validations
S1076	SB203580 SB203580 is a p38 MAPK inhibitor with IC50 of 0.3-0.5 μM in THP-1 cells, 10-fold less sensitive to SAPK3(106T) and SAPK4(106T) and blocks PKB phosphorylation with IC50 of 3-5 μM.	Cell Metab, 2020, 4;31(2):406-421 e7 Nat Commun, 2020, 11(1):37 Nat Commun, 2020, 8;11(1):2286	A, effects of p38 inhibitor SB203580 (1, 5, and 10 μM) on SRP72 protein expression was evaluated by WB using antibodies against human SRP72,SRP54, and GAPDH. A decreased intensity of SRP72 bands was noted when using the inhibitor at 5 μM concentration at 240 min (lane 6) and 10 μM at 120 and 240 min (lanes 8 and 9). B, results were analyzed and RUA illustrated, finding significant results at 5 μM, 240 versus 0 min, and 10 μM, 240 versus 0 and 120 versus 0 min, respectively, (p<0.05).
S1574	Doramapimod (BIRB 796) Doramapimod (BIRB 796) is a pan-p38 MAPK inhibitor with IC50 of 38 nM, 65 nM, 200 nM and 520 nM for p38α/β/γ/δ in cell-free assays, and binds p38α with K_d of 0.1 nM in THP-1 cells, 330-fold greater selectivity versus JNK2, weak inhibition for c-RAF, Fyn and Lck, insignificant inhibition of ERK-1, SYK, IKK2.	Genome Biol, 2020, 21(1):33 J Clin Invest, 2020, 130(3):1377-1391 Redox Biol, 2020, 28:101445	Effect of blockade of p38 or MEK on MK2 activation following TLR stimulation in moDC. MoDC were pre-treated with p38 inhibitors SB203580 10 mM (S), BIRB0796 (B) 0.1 or 1.0 mM or MEK inhibitor UO126 10 mM (U) for 1hr followed by poly I:C/R848 stimulation for 30 min then Western blotted for p-MK2 with β-actin loading control.
S1077	SB202190 (FHPI) SB202190 (FHPI) is a potent p38 MAPK inhibitor targeting p38α/β with IC50 of 50 nM/100 nM in cell-free assays, sometimes used instead of SB 203580 to investigate potential roles for SAPK2a/p38 in vivo.	Redox Biol, 2020, 28:101445 Cells, 2020, 13;9(5) pii: E1209 Cells, 2020, 28;9(4) pii: E822	C, Jurkat cells with SB202190 at 1, 5, and 10 μM were tested, and a decreased SRP72 expression was found when using at 10 μM (lanes 8 and 9). D, results were analyzed and RUA illustrated, finding significant results at 10 μM at 240 versus 0 and 120 versus 0 min (p<0.05).
S1494	Ralimetinib (LY2228820) Ralimetinib (LY2228820) is a novel and potent inhibitor of p38 MAPK with IC50 of 7 nM in a cell-free assay, does not alter p38 MAPK activation. Phase 1/2.	Genome Biol, 2020, 21(1):33 J Biol Chem, 2020, 10.1074/jbc.RA119.011633. Cancer Res Treat, 2020, 52(1):10-23	Relationship of JNK, p38 MAPK, and PI3K activation in TNF-α-induced signaling. Western blot analysis of the effect of another p38 MAPK inhibitor, LY2228820, on TNF-α signaling. HUVECs were pretreated with LY2228820 (10 umol/L) or wortmannin (1 umol/L) for 1 h, followed by stimulation with TNF-α (5 ng/mL) for 15 min (n=2).
S6005	VX-702 VX-702 is a highly selective inhibitor of p38α MAPK, 14-fold higher potency against the p38α versus p38β. Phase 2.	J Neurosci, 2020, 40(2):297-310 Int Immunopharmacol, 2020, 81:106143 Nat Cell Biol, 2019, 21(6):778-790	Reduction of IL-10 expression due to p38 inhibition is observed also in CpG-stimulated B cells and using VX-702. B cells were pre-treated with 10 uM of VX-702 for 1 h and stimulated with LPS or CpG for 24 or 48 h. Bar graphs indicate mean (±SEM) IL-10 concentrations at 48 h from n = 4 (LPS) and n = 3 (CpG) experiments. Significant differences against the no inhibitor condition were calculated using a paired Student's t-test and indicated as follows: p < 0.05, **p < 0.001.
S5183^New	PD 169316 PD 169316 is a potent, selective and cell-permeable p38 MAP kinase inhibitor with IC50 of 89 nM. PD169316 abrogates signaling initiated by both TGFbeta and Activin A. PD169316 shows antiviral activity against Enterovirus71.
S6807^New	TA-02 TA-02 is a p38 MAPK inhibitor with IC50 of 20 nM. TA-02 especially inhibits TGFBR-2.
S6502^New	SD 0006 SD0006 is an inhibitor of p38 kinase-alpha (p38alpha) with IC50 values of 0.016 μM and 0.677 μM for p38α and p38β. It is selective for p38α kinase over 50 other kinases screened (including p38γ and p38δ with modest selectivity over p38β).
S2726	PH-797804 PH-797804 is a novel pyridinone inhibitor of p38α with IC50 of 26 nM in a cell-free assay; 4-fold more selective versus p38β and does not inhibit JNK2. Phase 2.	Cell Metab, 2019, 29(1):141-155 Nat Commun, 2019, 10(1):448 Nat Commun, 2019, 10(1):3071	Effect of MEK inhibitor PH-797804 in A549 cells. A549 cells were incubated with increasing concentrations of PH-797804 for 2 h. The cell lysates were harvested and phosphorylation of indicated proteins was determined by Western blotting.
S1458	VX-745 VX-745 is a potent and selective inhibitor of p38α with IC50 of 10 nM, 22-fold greater selectivity versus p38β and no inhibition to p38γ.	Sci Rep, 2020, 10(1):3479 J Pharmacol Exp Ther, 2019, 370(2):219-230 J Biol Chem, 2018, 293(7):2302-2317	A) TRAP staining of BMMs cultured with M-CSF and RANKL for 7 d in the presence of SB203580 (50 nM) or VX-745 (50 nM). B) Bone slice assay indicated the effects of compounds on bone resorption.
S2928	TAK-715 TAK-715 is a p38 MAPK inhibitor for p38α with IC50 of 7.1 nM, 28-fold more selective for p38α over p38β, no inhibition to p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 or TAK1. Phase 2.	Nat Cell Biol, 2019, 21(6):778-790 J Pharmacol Exp Ther, 2019, 370(2):219-230
S3940	3'-Hydroxypterostilbene 3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium which may be useful in treating different types of haematological malignancies. 3'-Hydroxypterostilbene, a natural pterostilbene analogue, effectively inhibits the growth of human colon cancer cells (IC50s of 9.0, 40.2, and 70.9 µM for COLO 205, HCT-116, and HT-29 cells, respectively) by inducing apoptosis and autophagy. 3'-Hydroxypterostilbene inhibits the PI3K/Akt/mTOR/p70S6K, and p38MAPK pathways and activates the ERK1/2, JNK1/2 MAPK pathways.
S8125	Pamapimod Pamapimod (R-1503, Ro4402257) is a novel, selective inhibitor of p38 mitogen-activated protein kinase. It inhibits p38α and p38β enzymatic activity with IC50 values of 0.014±0.002 and 0.48± 0.04 microM, respectively with no activity against p38delta or p38gamma isoforms.	J Leukoc Biol, 2020, 10.1002/JLB.3A0120-379RR Nat Commun, 2019, 10(1):688 J Pharmacol Exp Ther, 2019, 370(2):219-230
S7741	SB239063 SB239063 is a potent and selective p38 MAPKα/β inhibitor with IC50 of 44 nM, showing no activity against the γ- and δ-kinase isoforms.	Redox Biol, 2020, 28:101445 Arch Toxicol, 2019, 93(5):1239-1253 J Cell Biochem, 2019, 120(9):14372-14382	KLF4 protein half-life is elongated under p38 inhibition. MCF7 cells plated in six-well plate were treated with DMSO or p38 inhibitors (SB203580 and SB239063) for 6 h. Then CHX was added 0, 2, 4 or 6 h before harvest. KLF4 protein level was tested by immunoblotting
S7214	Skepinone-L Skepinone-L is a selective p38α-MAPK inhibitor with IC50 of 5 nM.	Am J Physiol Renal Physiol, 2020, 318(2):F322-F328 Mol Cancer Ther, 2019, 18(9):1506-1519 Cancer Res, 2018, 78(5):1275-1292	TLR4/MAPK pathway regulated macrophage polarization towards M1 phenotype. LPS/INF-γ induced macrophages were cultured in the absence or presence of siTLR4, SP600125(an inhibitor of JNK), SCH772984(an inhibitor of ERK) and Skepinone-L(an inhibitor of p38) respectively for 24h. Then, all the cells were harvested for western blot assay.
S7215	Losmapimod (GW856553X) Losmapimod (GW856553X) is a selective, potent, and orally active p38 MAPK inhibitor with pK_i of 8.1 and 7.6 for p38α and p38β, respectively. Phase 3.	Front Immunol, 2020, 11:363 Cell Signal, 2020, 68:109528 J Neurogenet, 2018, 32(2):106-117	Intracellular pathways of b-adrenoceptor-induced proliferation. Urothelial proliferation (% of basal responses) in T24 in the absence and presence of (d) losmapimod (1-30 μM).
S9315	Praeruptorin A Praeruptorin A, a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. Praeruptorin A inhibits p38/Akt-c-Fos-NFATc1 signaling and PLCγ-independent Ca2+ oscillation. Praeruptorin A can significantly upregulates multidrug resistance-associated protein 2 expression via the constitutive androstane receptor-mediated pathway in vitro, and this should be taken as an herb-drug interaction.
S8124	BMS-582949 BMS-582949 is a potent and selective p38 mitogen-activated protein kinase (p38 MAPK) inhibitor with IC50 of 13nM,inhibiting both p38 kinase activity and activation of p38.	Onco Targets Ther, 2020, 13:2139-2151 Nat Commun, 2019, 10(1):688 J Exp Clin Cancer Res, 2019, 38(1):207
S7799	Pexmetinib (ARRY-614) Pexmetinib (ARRY-614) is a potent, orally bioavailable, dual p38 MAPK/Tie-2 inhibitor with IC50 of 4 nM/18 nM in a HEK-293 cell line. Phase 1.	J Pharmacol Exp Ther, 2019, 370(2):219-230
S8706	UM-164 UM-164 is a highly potent, dual c-Src/p38inhibitor of c-Src with a binding constant Kd of 2.7 nM for c-Src and inhibits both p38α and p38β.
S2266	Asiatic Acid Asiatic acid is the aglycone of asiaticoside isolated from the plant Centella asiatica, commonly used in wound healing.	Molecules, 2019, 24(12)
S9514	Rotundic acid Rotundic acid, a natural compound, exhibit cytotoxic activities toward human hepatocellular carcinoma (HepG2), malignant melanoma (A375), SCLC (NCI-H446), breast cancer (MCF-7), and colon cancer (HT-29) cell lines.RA induces cell cycle arrest, DNA damage, and apoptosis by modulating the AKT/mTOR and MAPK pathways.

Catalog No.	Information	Product Use Citations	Product Validations
S1076	SB203580 SB203580 is a p38 MAPK inhibitor with IC50 of 0.3-0.5 μM in THP-1 cells, 10-fold less sensitive to SAPK3(106T) and SAPK4(106T) and blocks PKB phosphorylation with IC50 of 3-5 μM.	Cell Metab, 2020, 4;31(2):406-421 e7 Nat Commun, 2020, 11(1):37 Nat Commun, 2020, 8;11(1):2286	A, effects of p38 inhibitor SB203580 (1, 5, and 10 μM) on SRP72 protein expression was evaluated by WB using antibodies against human SRP72,SRP54, and GAPDH. A decreased intensity of SRP72 bands was noted when using the inhibitor at 5 μM concentration at 240 min (lane 6) and 10 μM at 120 and 240 min (lanes 8 and 9). B, results were analyzed and RUA illustrated, finding significant results at 5 μM, 240 versus 0 min, and 10 μM, 240 versus 0 and 120 versus 0 min, respectively, (p<0.05).
S1574	Doramapimod (BIRB 796) Doramapimod (BIRB 796) is a pan-p38 MAPK inhibitor with IC50 of 38 nM, 65 nM, 200 nM and 520 nM for p38α/β/γ/δ in cell-free assays, and binds p38α with K_d of 0.1 nM in THP-1 cells, 330-fold greater selectivity versus JNK2, weak inhibition for c-RAF, Fyn and Lck, insignificant inhibition of ERK-1, SYK, IKK2.	Genome Biol, 2020, 21(1):33 J Clin Invest, 2020, 130(3):1377-1391 Redox Biol, 2020, 28:101445	Effect of blockade of p38 or MEK on MK2 activation following TLR stimulation in moDC. MoDC were pre-treated with p38 inhibitors SB203580 10 mM (S), BIRB0796 (B) 0.1 or 1.0 mM or MEK inhibitor UO126 10 mM (U) for 1hr followed by poly I:C/R848 stimulation for 30 min then Western blotted for p-MK2 with β-actin loading control.
S1077	SB202190 (FHPI) SB202190 (FHPI) is a potent p38 MAPK inhibitor targeting p38α/β with IC50 of 50 nM/100 nM in cell-free assays, sometimes used instead of SB 203580 to investigate potential roles for SAPK2a/p38 in vivo.	Redox Biol, 2020, 28:101445 Cells, 2020, 13;9(5) pii: E1209 Cells, 2020, 28;9(4) pii: E822	C, Jurkat cells with SB202190 at 1, 5, and 10 μM were tested, and a decreased SRP72 expression was found when using at 10 μM (lanes 8 and 9). D, results were analyzed and RUA illustrated, finding significant results at 10 μM at 240 versus 0 and 120 versus 0 min (p<0.05).
S1494	Ralimetinib (LY2228820) Ralimetinib (LY2228820) is a novel and potent inhibitor of p38 MAPK with IC50 of 7 nM in a cell-free assay, does not alter p38 MAPK activation. Phase 1/2.	Genome Biol, 2020, 21(1):33 J Biol Chem, 2020, 10.1074/jbc.RA119.011633. Cancer Res Treat, 2020, 52(1):10-23	Relationship of JNK, p38 MAPK, and PI3K activation in TNF-α-induced signaling. Western blot analysis of the effect of another p38 MAPK inhibitor, LY2228820, on TNF-α signaling. HUVECs were pretreated with LY2228820 (10 umol/L) or wortmannin (1 umol/L) for 1 h, followed by stimulation with TNF-α (5 ng/mL) for 15 min (n=2).
S6005	VX-702 VX-702 is a highly selective inhibitor of p38α MAPK, 14-fold higher potency against the p38α versus p38β. Phase 2.	J Neurosci, 2020, 40(2):297-310 Int Immunopharmacol, 2020, 81:106143 Nat Cell Biol, 2019, 21(6):778-790	Reduction of IL-10 expression due to p38 inhibition is observed also in CpG-stimulated B cells and using VX-702. B cells were pre-treated with 10 uM of VX-702 for 1 h and stimulated with LPS or CpG for 24 or 48 h. Bar graphs indicate mean (±SEM) IL-10 concentrations at 48 h from n = 4 (LPS) and n = 3 (CpG) experiments. Significant differences against the no inhibitor condition were calculated using a paired Student's t-test and indicated as follows: p < 0.05, **p < 0.001.
S5183^New	PD 169316 PD 169316 is a potent, selective and cell-permeable p38 MAP kinase inhibitor with IC50 of 89 nM. PD169316 abrogates signaling initiated by both TGFbeta and Activin A. PD169316 shows antiviral activity against Enterovirus71.
S6807^New	TA-02 TA-02 is a p38 MAPK inhibitor with IC50 of 20 nM. TA-02 especially inhibits TGFBR-2.
S6502^New	SD 0006 SD0006 is an inhibitor of p38 kinase-alpha (p38alpha) with IC50 values of 0.016 μM and 0.677 μM for p38α and p38β. It is selective for p38α kinase over 50 other kinases screened (including p38γ and p38δ with modest selectivity over p38β).
S2726	PH-797804 PH-797804 is a novel pyridinone inhibitor of p38α with IC50 of 26 nM in a cell-free assay; 4-fold more selective versus p38β and does not inhibit JNK2. Phase 2.	Cell Metab, 2019, 29(1):141-155 Nat Commun, 2019, 10(1):448 Nat Commun, 2019, 10(1):3071	Effect of MEK inhibitor PH-797804 in A549 cells. A549 cells were incubated with increasing concentrations of PH-797804 for 2 h. The cell lysates were harvested and phosphorylation of indicated proteins was determined by Western blotting.
S1458	VX-745 VX-745 is a potent and selective inhibitor of p38α with IC50 of 10 nM, 22-fold greater selectivity versus p38β and no inhibition to p38γ.	Sci Rep, 2020, 10(1):3479 J Pharmacol Exp Ther, 2019, 370(2):219-230 J Biol Chem, 2018, 293(7):2302-2317	A) TRAP staining of BMMs cultured with M-CSF and RANKL for 7 d in the presence of SB203580 (50 nM) or VX-745 (50 nM). B) Bone slice assay indicated the effects of compounds on bone resorption.
S2928	TAK-715 TAK-715 is a p38 MAPK inhibitor for p38α with IC50 of 7.1 nM, 28-fold more selective for p38α over p38β, no inhibition to p38γ/δ, JNK1, ERK1, IKKβ, MEKK1 or TAK1. Phase 2.	Nat Cell Biol, 2019, 21(6):778-790 J Pharmacol Exp Ther, 2019, 370(2):219-230
S3940	3'-Hydroxypterostilbene 3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium which may be useful in treating different types of haematological malignancies. 3'-Hydroxypterostilbene, a natural pterostilbene analogue, effectively inhibits the growth of human colon cancer cells (IC50s of 9.0, 40.2, and 70.9 µM for COLO 205, HCT-116, and HT-29 cells, respectively) by inducing apoptosis and autophagy. 3'-Hydroxypterostilbene inhibits the PI3K/Akt/mTOR/p70S6K, and p38MAPK pathways and activates the ERK1/2, JNK1/2 MAPK pathways.
S8125	Pamapimod Pamapimod (R-1503, Ro4402257) is a novel, selective inhibitor of p38 mitogen-activated protein kinase. It inhibits p38α and p38β enzymatic activity with IC50 values of 0.014±0.002 and 0.48± 0.04 microM, respectively with no activity against p38delta or p38gamma isoforms.	J Leukoc Biol, 2020, 10.1002/JLB.3A0120-379RR Nat Commun, 2019, 10(1):688 J Pharmacol Exp Ther, 2019, 370(2):219-230
S7741	SB239063 SB239063 is a potent and selective p38 MAPKα/β inhibitor with IC50 of 44 nM, showing no activity against the γ- and δ-kinase isoforms.	Redox Biol, 2020, 28:101445 Arch Toxicol, 2019, 93(5):1239-1253 J Cell Biochem, 2019, 120(9):14372-14382	KLF4 protein half-life is elongated under p38 inhibition. MCF7 cells plated in six-well plate were treated with DMSO or p38 inhibitors (SB203580 and SB239063) for 6 h. Then CHX was added 0, 2, 4 or 6 h before harvest. KLF4 protein level was tested by immunoblotting
S7214	Skepinone-L Skepinone-L is a selective p38α-MAPK inhibitor with IC50 of 5 nM.	Am J Physiol Renal Physiol, 2020, 318(2):F322-F328 Mol Cancer Ther, 2019, 18(9):1506-1519 Cancer Res, 2018, 78(5):1275-1292	TLR4/MAPK pathway regulated macrophage polarization towards M1 phenotype. LPS/INF-γ induced macrophages were cultured in the absence or presence of siTLR4, SP600125(an inhibitor of JNK), SCH772984(an inhibitor of ERK) and Skepinone-L(an inhibitor of p38) respectively for 24h. Then, all the cells were harvested for western blot assay.
S7215	Losmapimod (GW856553X) Losmapimod (GW856553X) is a selective, potent, and orally active p38 MAPK inhibitor with pK_i of 8.1 and 7.6 for p38α and p38β, respectively. Phase 3.	Front Immunol, 2020, 11:363 Cell Signal, 2020, 68:109528 J Neurogenet, 2018, 32(2):106-117	Intracellular pathways of b-adrenoceptor-induced proliferation. Urothelial proliferation (% of basal responses) in T24 in the absence and presence of (d) losmapimod (1-30 μM).
S9315	Praeruptorin A Praeruptorin A, a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. Praeruptorin A inhibits p38/Akt-c-Fos-NFATc1 signaling and PLCγ-independent Ca2+ oscillation. Praeruptorin A can significantly upregulates multidrug resistance-associated protein 2 expression via the constitutive androstane receptor-mediated pathway in vitro, and this should be taken as an herb-drug interaction.
S8124	BMS-582949 BMS-582949 is a potent and selective p38 mitogen-activated protein kinase (p38 MAPK) inhibitor with IC50 of 13nM,inhibiting both p38 kinase activity and activation of p38.	Onco Targets Ther, 2020, 13:2139-2151 Nat Commun, 2019, 10(1):688 J Exp Clin Cancer Res, 2019, 38(1):207
S7799	Pexmetinib (ARRY-614) Pexmetinib (ARRY-614) is a potent, orally bioavailable, dual p38 MAPK/Tie-2 inhibitor with IC50 of 4 nM/18 nM in a HEK-293 cell line. Phase 1.	J Pharmacol Exp Ther, 2019, 370(2):219-230
S8706	UM-164 UM-164 is a highly potent, dual c-Src/p38inhibitor of c-Src with a binding constant Kd of 2.7 nM for c-Src and inhibits both p38α and p38β.

Catalog No.	Information	Product Use Citations	Product Validations
S2266	Asiatic Acid Asiatic acid is the aglycone of asiaticoside isolated from the plant Centella asiatica, commonly used in wound healing.	Molecules, 2019, 24(12)

Catalog No.

Information

Product Use Citations

Product Validations

S2266

Asiatic Acid

Asiatic acid is the aglycone of asiaticoside isolated from the plant Centella asiatica, commonly used in wound healing.

Molecules, 2019, 24(12)

Catalog No.	Information	Product Use Citations	Product Validations
S9514	Rotundic acid Rotundic acid, a natural compound, exhibit cytotoxic activities toward human hepatocellular carcinoma (HepG2), malignant melanoma (A375), SCLC (NCI-H446), breast cancer (MCF-7), and colon cancer (HT-29) cell lines.RA induces cell cycle arrest, DNA damage, and apoptosis by modulating the AKT/mTOR and MAPK pathways.

Catalog No.

Information

Product Use Citations

Product Validations

S9514

Rotundic acid, a natural compound, exhibit cytotoxic activities toward human hepatocellular carcinoma (HepG2), malignant melanoma (A375), SCLC (NCI-H446), breast cancer (MCF-7), and colon cancer (HT-29) cell lines.RA induces cell cycle arrest, DNA damage, and apoptosis by modulating the AKT/mTOR and MAPK pathways.