jak3-in-1

JAK3-IN-1 is an orally active, selective and potent JAK3 inhibitor that can be used to study immune system diseases.

JAK3-IN-11 (Compound 12) exhibits potent, noncytotoxic, irreversible, orally active JAK3 inhibitory activity (IC50 = 1.7 nM) with an excellent selectivity profile (>588-fold compared to other JAK isoforms), covalently binds to the ATP-binding pocket in JAK3. JAK3-IN-11 strongly inhibits JAK3-dependent signaling and T-cell proliferation which is a promising tool for studying autoimmune diseases [1].

JAK3 BTk-in-1 is a dual JAK3 BTK inhibitor that specifically targets and inhibits Janus kinase 3 (JAK3) and Bruton's tyrosine kinase (BTK), two important targets in autoimmune diseases. JAK3 BTk-in-1 simultaneously inhibited the BTK JAK3 signaling pathway, showing a synergistic effect. JAK3 BTK-in-1 is a potential compound for the treatment of immune-related diseases, such as autoimmune diseases, certain types of cancer (including lymphoma and leukemia), and other diseases that may be characterized by an unbalanced immune response.

JAK3-IN-14 is a potent, selective and orally active FLT3 inhibitor, with IC50s of ∼40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively.

JAK3-IN-16 (compound 6) is a covalent inhibitor of JAK3.

JAK3-IN-12 (compound 15k) is a potent inhibitor of JAK3 (IC50: 9.5 nM) and can be used in the study of rheumatoid arthritis.

JAK3-IN-15 (compound 22) is a JAK3 inhibitor that reduces the secretion of p-JAK3 induced by LPS. It is utilized in research for rheumatoid arthritis.

JAK3-IN-13 is a potent, selective, orally active JAK3 inhibitor with IC50 values of 4728 nM for NK1, 2039 nM for JNK2, 8 nM for JNK3, and 365 nM for Tyk2. JAK3-IN-13 also exhibits anti-tumor effects.

JAK3 BTK-IN-7 (XL-12), characterized as a JAK3 BTK inhibitor, exhibits IC 50 values of 2 nM and 14 nM for JAK3 and BTK respectively. This compound demonstrates anti-inflammatory properties and is applicable in research related to rheumatoid arthritis [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].

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].

TK4b can be used in the research of leukemia cancer and lymphoid-derived diseases. TK4b is a Janus kinase (JAK) inhibitor with the IC50 values of 18.42 nM and 19.40 nM for JAK3 and JAK2, respectively [1].

JAK3-IN-9 is a potent and orally active inhibitor of the Janus kinase 3 (JAK3) enzyme, displaying an impressive IC50 value of 1.7 nM. It exhibits high selectivity towards the JAK3 signaling pathway, making it a valuable tool for studying autoimmune diseases. Additionally, JAK3-IN-9 possesses desirable characteristics such as low toxicity and excellent oral bioavailability. It also demonstrates promising anti-arthritis activity, thus enhancing its potential as a therapeutic agent [1].

JAK kinase-IN-1 (Example 1) is a potent inhibitor targeting the JAK family, including TYK2, JAK1, JAK2, and JAK3, with IC50 values of 4.2 nM, 32 nM, 27 nM, and 3473 nM, respectively [1].

JAK2 FLT3-IN-1 (TFA) is an orally active dual inhibitor of JAK2 (IC50: 0.7 nM) and FLT3 (IC50: 4 nM) that demonstrates anticancer effects, also affecting JAK1 (IC50: 26 nM) and JAK3 (IC50: 39 nM).

JAK-IN-34 (compound 11n) is a potent inhibitor of Janus kinases (JAKs), demonstrating IC50 values of 0.40 nM for JAK1, 0.83 nM for JAK2, 2.10 nM for JAK3, and 1.95 nM for TYK2. It effectively reduces joint swelling while maintaining a good safety profile [1].

JAK2-IN-7, a selective inhibitor targeting Janus Kinase 2 (JAK2), exhibits inhibitory concentrations (IC50) of 3 nM for JAK2, 11.7 nM for SET-2 cells, and 41 nM for Ba F3 V617F cells, indicative of its potency and selectivity. This compound demonstrates more than 14-fold selectivity against JAK1, JAK3, and FLT3, underlining its specificity. JAK2-IN-7 effectively induces cell cycle arrest at the G0 G1 phase and promotes apoptosis in tumor cells, manifesting significant antitumor activities [1].

JAK-IN-1 shows improved selectivity for JAK3 over JAK1. JAK-IN-1 is a JAK1 2 3 inhibitor with IC50s of 0.26, 0.8 and 3.2 nM, respectively.

JAK-IN-31 (Example 75), a JAK inhibitor, demonstrates IC50 values of ≤0.01 µM for JAK1, ≤0.01 µM for JAK2, 0.01-0.1 µM for JAK3, and ≤0.01 µM for Tyk2, indicating potent activity across these targets. It is utilized in cancer research [1].

JAK-IN-25 (compound 19), a potent JAK inhibitor, exhibits IC50 values of 6 nM for TYK2, 21 nM for JAK1, 8 nM for JAK2, and 1051 nM for JAK3. It also demonstrates an IC50 of 28 nM against human whole blood IL-12 (HEB IL-12) and holds potential for cancer research [1].

FAK-IN-22 (Compound 26) is an inhibitor of FAK, JAK3, and Aurora B, with IC50 values of 50.94 nM, 9.99 nM, and 0.49 nM, respectively, effectively suppressing tumorigenesis and metastasis in pancreatic ductal adenocarcinoma (PDAC). It inhibits proliferation in PANC-1 cells with an IC50 of 0.15 μM. FAK-IN-22 induces apoptosis and G2 M phase arrest in PANC-1 cells by inhibiting the FAK PI3K Akt signaling pathway.

Flonoltinib (JAK2 FLT3-IN-1) is an orally active and potent JAK2 FLT3 inhibitor, inhibiting JAK2, FLT3, JAK1, and JAK3. Flonoltinib has anti-cancer activity and can be used for studying myeloproliferative neoplasms.

Flonoltinib maleate is an orally effective dual JAK2 FLT3 inhibitor, with IC50 values of 0.7 nM for JAK2, 4 nM for FLT3, 26 nM for JAK1, and 39 nM for JAK3. Known as JAK2 FLT3-IN-1, it exhibits anticancer activity.

BMX-IN-1 (BMX kinase inhibitor) is a selective inhibitor of bone marrow tyrosine kinase on chromosome X (BMX, IC50 = 8 nM) and the related Bruton's tyrosine kinase (BTK, IC50 = 10.4 nM), but BMX-IN-1 is more than 47-656 fold less potent against Blk, JAK3, EGFR, Itk, or Tec activity.