jak in 4

JAK-IN-4 is a prodrug of a JAK inhibitor, effective in murine collagen induced arthritis model.

JAK2-IN-4 is a selective JAK2/JAK3 inhibitor, with IC50 values of 0.7 nM and 23.2 nM for JAK2 and JAK3, respectively.

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).

JAK/HDAC-IN-4 (compound 11 i) is a dual inhibitor targeting both JAK2 and HDAC6, with IC50 values of 0.49 nM and 12 nM respectively. It inhibits cell proliferation and the production of nitric oxide. In a mouse model induced by Imiquimod, JAK/HDAC-IN-4 ameliorates psoriasiform skin lesions with low toxicity.

JAK1/TYK2-IN-4 serves as a dual inhibitor targeting both JAK and TYK2, displaying IC50 values of 39 nM and 21 nM, respectively. It is also orally bioavailable [1].

PROTACFLT3/JAK2/BRD4 Degrader-1 is a PROTAC degrader targeting FLT3, JAK2, and BRD4, with DC50 values of 5.23 nM, 0.678 nM, and 1.17 nM, respectively. It exhibits potent antiproliferative activity against MV4;11 cells (IC50= 0.79 nM) and FLT3-mutated Ba/F3 cells. Additionally, PROTACFLT3/JAK2/BRD4 Degrader-1 induces apoptosis in MV4;11 cells and demonstrates significant antitumor efficacy in an MV4;11 xenograft model established in NOD SCID mice. This compound is applicable for research in acute myeloid leukemia (AML).

JAK3/BTK-IN-4 is a potent inhibitor of JAK3/BTK, targeting critical pathways in autoimmune diseases. The simultaneous inhibition of the BTK/JAK3 signaling pathway exerts a synergistic effect, making JAK3/BTK-IN-4 a promising therapeutic candidate for JAK3 kinase and/or BTK-related diseases.

HDAC/JAK/BRD4-IN-1 (compound 25ap) is a potent triple inhibitor targeting HDAC, JAK, and BRD4. This compound not only inhibits cell proliferation but also induces apoptosis in MDA-MB-231 cells and demonstrates in vivo anticancer efficacy [1].

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.

WHI-P97 HCl is a potent and selective JAK-3 inhibitor. WHI-P97 had an estimated Ki value of 0.09 microM from modeling studies and a measured IC50 value of 2.5 microM in EGFR kinase inhibition assays. WHI-P97 effectively inhibited the in vitro invasiveness of EGFR-positive human cancer cells in a concentration-dependent manner.

Gusacitinib, also known as ASN-002 and EN-3351, is a potent dual inhibitor of SYK/JAK kinases. ASN002 showed strong antitumor activity in both hematological and solid tumor xenograft models. ASN002 strongly suppressed the SYK and JAK family kinase signaling pathways as measured in pLAT and pSTAT assays, respectively. When profiled in a panel of 178 cell lines, ASN002 showed strong anti-proliferative activity in many lymphoid/leukemia cell lines, including SU-DHL-6, SU-DHL-4, OCI-LY10, H929 and Pfeiffer.

JAK-IN-24, a JAK inhibitor, exhibits IC50 values of 0.534 nM and 24 nM in the presence of 4 μM and 1 mM ATP, respectively. Additionally, it effectively inhibits STAT5 phosphorylation induced by PBMC IL-15 with an IC50 of 86.171 nM.

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].