p38γ Inhibitor

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.

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.

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.

JNJ-49095397 (RV568) is an inhaled narrow-spectrum kinase inhibitor (NSKI) against both the α and γ isoforms of p38 MAPK. JNJ-49095397 also inhibits SRC kinase family, specifically haematopoietic kinase (HCK) JNJ-49095397 shows potent anti-inflammatory effects and can be used for the research of chronic obstructive pulmonary disease (COPD) and asthma.

SX 011 is a p38 inhibitor with IC₅₀s of 9 nM and 90 nM against p38α and p38β, respectively. SX 011 also inhibits JNK-2 with an IC₅₀ of 100 nM. SX-011 is orally bioavailable.

p38-α MAPK-IN-5 (compound 4e) is a potent p38α inhibitor with IC₅₀s of 0.1 nM, 0.2 nM, 944 nM, 4100 nM for p38α, p38 β, p38γ, p38δ, respectively. p38-α MAPK-IN-5 has anti-inflammatory effect. p38-α MAPK-IN-5 has the potential for asthma and chronic obstructive pulmonary disease (COPD) research.

AMG-548 hydrochloride, 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 hydrochloride is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC₅₀=3 nM). AMG-548 hydrochloride inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε.

P38-α MAPK-IN-11 (Compound 4C) is a selective inhibitor of P38α MAPK that can cross the blood-brain barrier with an IC₅₀ value of 43 nM. P38-α MAPK-IN-11 has extremely low inhibitory activity against other MAPK subtypes, namely p38β, p38γ, and p38δ, with IC₅₀ values of > 100 nM, > 100 nM, and 48.6 mM respectively. P38-α MAPK-IN-11 exhibits outstanding neuroprotective effects and anti-neuroinflammatory effects in Alzheimer's disease-like rat models. P38-α MAPK-IN-11 can be used for the study of Alzheimer's disease.

Doramapimod GMP (BIRB 796 GMP) is an orally active inhibitor for p38 MAPK, with IC₅₀s of 38, 65, 200 and 520 nM, for p38α, p38β, p38γ, p38δ. Doramapimod exhibits cytotoxicity and antitumor activity against multiple myeloma, synergizes with multidrug resistance protein 1 (ABCB1) and aurora kinase inhibitor VX680, promoting their antitumor efficacy against oral epidermoid carcinoma and cervical cancer. Doramapimod also exhibits anti-inflammatory activity.