p38α Inhibitor

SB 202190 is a selective p38 MAP kinase inhibitor with IC₅₀s of 50 nM and 100 nM for p38α and p38β2, respectively. SB 202190 binds to the ATP pocket of the active recombinant human p38 kinase with a K_d of 38 nM. SB 202190 has anti-cancer activity and rescued memory deficits. SB202190 induces autophagy.

Doramapimod (BIRB 796) is an orally active, highly potent p38 MAPK inhibitor, which has an IC₅₀ for p38α=38 nM, for p38β=65 nM, for p38γ=200 nM, and for p38δ=520 nM. Doramapimod has picomolar affinity for p38 kinase (K_d=0.1 nM). Doramapimod also inhibits B-Raf with an IC₅₀ of 83 nM.

Naporafenib (LXH254) is a potent, selective, orally active, type II BRAF and CRAF inhibitor, with IC₅₀ values of 0.072 and 0.21 nM against CRAF and BRAF, respectively.

Ralimetinib dimesylate (LY2228820 dimesylate) is a selective, ATP-competitive inhibitor of p38 MAPK α/β with IC₅₀s of 5.3 and 3.2 nM, respectively. Ralimetinib (LY2228820) selectively inhibits phosphorylation of MK2 (Thr334), with no effect on phosphorylation of p38a MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc.

Neflamapimod (VX-745) is a potent, blood-brain barrier penetrant, highly selective inhibitor of p38α inhibitor with an IC₅₀ for p38α of 10 nM and for p38β of 220 nM. Neflamapimod (VX-745) possesses anti-inflammatory activity.

p38α-IN-14 is a selective p38α inhibitor with an IC₅₀ of 65 nM. p38α-IN-14 exhibits only weak inhibitory activity against hERG channels, with an IC₅₀ > 30 μM. p38α-IN-14 can be used in the research of chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, psoriasis and inflammatory bowel disease.

R-130823 is an orally active, highly selective p38α inhibitor with an IC₅₀ of 22 nM against p38α, an IC₅₀ of 820 nM against p38β, and no activity against p38γ or p38δ. R-130823 downregulates downstream cartilage degradation and inflammatory mediators, and inhibits the release of MMP-13, MMP-1 and PGE2. R-130823 reduces hind paw swelling, improves hyperalgesia, and blocks arthritis progression. R-130823 is applicable to research related to osteoarthritis and rheumatoid arthritis.

SB 202190 hydrochloride is a selective p38 MAP kinase inhibitor with IC₅₀s of 50 nM and 100 nM for p38α and p38β2, respectively. SB 202190 hydrochloride binds to the ATP pocket of the active recombinant human p38 kinase with a K_d of 38 nM. SB 202190 hydrochloride has anti-cancer activity. SB202190 hydrochloride induces autophagy.

TAK-715 is an orally active and potent p38 MAPK inhibitor with IC₅₀s of 7.1 nM, 200 nM for p38α and p38β, respectively. TAK-715 inhibits casein kinase I (CK1δ/ε) to regulate activation of Wnt/β-catenin signaling. TAK-715 shows good significant efficacy in a rat arthritis model.

AMG-548 dihydrochloride, an orally active and selective p38α inhibitor (K_i=0.5 nM), shows slightly selective over p38β (K_i=36 nM) and >1000 fold selective against p38γ and p38δ. AMG-548 dihydrochloride is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC₅₀=3 nM). AMG-548 dihydrochloride inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε.

Talmapimod (SCIO-469) is an orally active and selective inhibitor of p38α MAPK with an IC₅₀ of 9 nM. Talmapimod inhibits the secretion of inflammatory factors (such as TNFα, IL-1β, IL-6, and VEGF) by suppressing the p38α MAPK pathway, and it also inhibits angiogenesis and osteoclast activation. Talmapimod inhibits the growth of multiple myeloma cells and induces apoptosis. Talmapimod can be used to study various hematological malignancies (such as multiple myeloma, myelodysplastic syndrome).

Pamapimod (Ro4402257) is a potent, selective and orally active p38 MAPK inhibitor with IC₅₀s of 14 nM and 480 nM and K_is of 1.3 nM and 120 nM for p38α and p38β, respectively. Pamapimod has no activity against p38δ or p38γ isoforms. Pamapimod has the potential for rheumatoid arthritis and other autoimmune diseases treatment.

SR-318, a chemical probe, is a potent and highly selective p38 MAPK inhibitor with IC₅₀s of 5 nM, 32 nM and 6.11 μM for p38α, p38β and p38α/β, respectively. SR-318 potently inhibits the TNF-α release in whole blood with an IC₅₀ of 283 nM. SR-318 has anti-cancer and anti-inflammatory activity.

AMG-548, an orally active and selective p38α inhibitor (K_i=0.5 nM), shows slightly selective over p38β (K_i=36 nM) and >1000 fold selective against p38γ and p38δ. AMG 548 is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC₅₀=3 nM). AMG-548 inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε.

Ralimetinib is an ATP-competitive p38α and p38β MAPK inhibitor with an IC₅₀ of 5.3 nmol/L against human p38α and an IC₅₀ of 3.2 nmol/L against human p38β. Ralimetinib slows tumor growth in preclinical in vivo cancer models, exhibits oral bioavailability in mice, and achieves sustained target inhibition for 4 to 8 h. Ralimetinib is applicable for research on melanoma, non-small cell lung cancer, ovarian cancer, glioma, multiple myeloma, breast cancer, renal cancer, and head and neck squamous cell carcinoma.

UM-164 (DAS-DFGO-II) is a highly potent inhibitor of c-Src with a K_d of 2.7 nM. UM-164 also potently inhibits p38α and p38β.

EW-7195 is a potent and selective ALK5 (TGFβR1) inhibitor with an IC₅₀ of 4.83 nM. EW-7195 has >300-fold selectivity for ALK5 over p38α. EW-7195 efficiently inhibits TGF-β1-induced Smad signaling, epithelial-to-mesenchymal transition (EMT) and breast tumour metastasis to the lung.

CK1-IN-1 (Compound 1c) is a casein kinase 1 (CK1) inhibitor with IC₅₀ values of 15 nM and 16 nM for CK1δ and CK1ε, respectively. CK1-IN-1 inhibits p38α MAPK with an IC₅₀ of 73 nM. CK1-IN-1 can be used to study cardiomyogenesis.

RWJ-67657 (JNJ 3026582) is an orally active and selective p38α and p38β MAPK inhibitor with IC₅₀s of 1 and 11 μM, respectively. RWJ-67657 displays no activity at p38γ and p38δ, and exhibits cardio protective effect. Anti-inflammatory and anti-tumor activity.

R1487 Hydrochloride is a highly potent and selective p38α inhibitor, with K_d values of 0.2 nM and 29 nM for p38α and p38β, respectively.