jak1-stat3

JAK1 STAT3-IN-1 (compound 4f) functions as an anti-atopic dermatitis (AD) agent by inhibiting the JAK1 STAT3 signaling pathway. It has an IC50 value of 2.17 μM for inhibiting NO production. Additionally, JAK1 STAT3-IN-1 improves skin conditions in AD-like mice by reducing inflammatory infiltration, suppressing the expression of p-JAK1 JAK1 and p-STAT3 STAT3, and alleviating the hyperimmune response induced by MC903 (Calcipotriol).

Abrocitinib (PF-04965842) (PF-04965842) is a potent, specific and orally-active JAK1 inhibitor (IC50s: 29 803 nM for JAK1 2).

WP1066 is a inhibitor of JAK2 (IC50: 2.30 μM) and STAT3 (IC50: 2.43 μM) in HEL cells; shows activity to JAK2, STAT3 5, and ERK1 2, not JAK1 and JAK3. WP1066 has been used in trials studying the treatment of Melanoma, Brain Cancer, Solid Tumors, and Central Nervous System Neoplasms.

JAK1-IN-4 is a selective JAK1 inhibitor (IC50s: 85 nM, 12.8 μM and >30 μM for JAK1, JAK2, and JAK3, respectively). JAK1-IN-4 inhibits STAT3 phosphorylation in NCI-H 1975 cells (IC50, 227 nM).

JAK1-IN-16 (compound 4l) acts as an inhibitor of JAK1 STAT3 and effectively downregulates the expression of TLR4 protein.

JAK-IN-40 (Compound 46) is an inhibitor of JAK, effectively targeting JAK1, JAK2, and JAK3 with IC50 values of 0.022, 0.759, and 1.601 μM, respectively. It reduces the phosphorylation of STAT3 and inhibits the proliferation of cancer cells Ba F3 and JAK1-TEL Ba F3 with GI50 values of 0.614 μM and 0.193 μM. JAK-IN-40 arrests cell cycle progression at the G2 M phase in H1975 and H2087 cells, leading to apoptosis. Additionally, JAK-IN-40 exhibits a synergistic anti-tumor effect when used in combination with Osimertinib.

K882 (Compound 4e) is an Src inhibitor with a KD of 0.315 μM. It induces apoptosis and inhibits XIAP and Survivin. Additionally, K882 blocks the activation of the PI3K Akt mTOR, Jak1 Stat3, and Ras MAPK signaling pathways. K882 exhibits antitumor activity against non-small cell lung cancer.

XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, 100 fold selectivity over JAK1.

INCB16562 is a novel, selective, and orally bioavailable small-molecule inhibitor of JAK1 and JAK2 markedly selective over JAK3. Treatment of myeloma cells with INCB16562 potently inhibited interleukin-6 (IL-6)-induced phosphorylation of STAT3. INCB16562 abrogated the protective effects of recombinant cytokines or bone marrow stromal cells and sensitized myeloma cells to cell death by exposure to dexamethasone, melphalan, or bortezomib. Oral administration of INCB16562 antagonized the growth of myeloma xenografts in mice and enhanced the antitumor activity of relevant agents in combination studies. INCB16562 is a potent JAK1 2 inhibitor and that mitigation of JAK STAT signaling by targeting JAK1 and JAK2 will be beneficial in the treatment of myeloma patients, particularly in combination with other agents. ( source: Neoplasia. 2010 Jan;12(1):28-38. ).

JI069 (WAY-354189) is a potent STAT3 inhibitor that inhibits gp130 signaling by inducing dissociation between gp130 and JAK1.

JAK HDAC-IN-2, a potent 2-amino-4-phenylaminopyrimidine dual-target inhibitor, effectively suppresses JAK1 2 and HDAC3 6 at nanomolar concentrations. This compound exhibits proapoptotic properties, inhibits histone deacetylation, and impedes STAT3 phosphorylation, demonstrating notable antiproliferative activity against various hematological malignancies and solid tumors [1].

JAK-IN-27, also known as compound 1, is an orally active, potent inhibitor of the JAKS family kinases, displaying inhibitory concentrations (IC50s) of 3.0 nM for TYK2, 7.7 nM for JAK1, and 629.6 nM for JAK3. Moreover, JAK-IN-27 impedes IFN-α2B-induced phosphorylation of STAT3 in Jurkat cells with an IC50 of 23.7 nM [1].

Ivarmacitinib (SHR0302) sulfate, a potent and orally active inhibitor of all JAK family members, exhibits particular selectivity towards JAK1. Its selectivity is >10-fold greater for JAK1 compared to JAK2, 77-fold more than JAK3, and 420-fold more than Tyk2. Ivarmacitinib effectively inhibits JAK1-STAT3 phosphorylation, thereby inducing apoptosis in hepatic stellate cells. Additionally, it demonstrates notable anti-proliferative and anti-inflammatory properties [1] [2].

JAK1-IN-13 (compound 36b) functions as an orally active, potent, and highly selective JAK1 inhibitor, exhibiting an IC 50 of 0.044 nM. It effectively reduces STAT3 phosphorylation [1].

MMT3-72 is a weak JAK1 inhibitor with superior efficacy and reduced p-STAT3 in DSS-induced colitis [1].

SHR0302 (ARQ252) is a JAK inhibitor that binds JAK1 with stronger affinity than others (Selectivity for JAK1 is more than 10 times for JAK2, 77 times for JAK3, 420 times for Tyk2).