JAK Inhibitor

AUH-6-96 is a JAK/STAT signaling inhibitor. AUH-6-96 reduces Unpaired-induced transcriptional activity in Drosophila cells and blocks tyrosine phosphorylation of STAT92E. AUH-6-96 blocks both constitutive and IL-6-induced phosphorylation of STAT3. AUH-6-96 decreases the level of tyrosine-phosphorylated JAK3. AUH-6-96 induces cancer cell Apoptosis by downregulating the expression of anti-apoptotic genes downstream of STAT3. AUH-6-96 selectively reduces the viability of cancer cells with abnormal JAK/STAT signaling pathway. AUH-6-96 is applicable to related research on Hodgkin's lymphoma, breast cancer, and prostate cancer.

SIRT5-IN-10 is a competitive SIRT5 inhibitor. SIRT5-IN-10 improves renal function and reduces histopathological damage in septic acute kidney injury (AKI) mice. SIRT5-IN-10 can be used for the research of sepsis-associated AKI.

JAK2/STAT3-IN-2 is an orally active JAK2/STAT3 inhibitor. JAK2/STAT3-IN-2 inhibits the phosphorylation of tyrosine residues in JAK2 and STAT3, blocks downstream signal transduction, disrupts the dimerization and nuclear translocation of STAT3, and suppresses pro-inflammatory transcriptional activity. JAK2/STAT3-IN-2 inhibits the expression of IL-17A and IL-17F, reduces immune cell infiltration, and inhibits the production of NO simultaneously. JAK2/STAT3-IN-2 exerts a protective effect in a mouse model of ulcerative colitis induced by DSS (HY-116282C). JAK2/STAT3-IN-2 can be used for the research of ulcerative colitis.

JAK3-IN-14 (compound 1) is a potent JAK3 inhibitor, with IC₅₀ values of 38 and 600 nM for JAK3 and JAK2, respectively. JAK3-IN-14 shows inhibitory of IL-4 and IL-3 induced TF-1 cell proliferation, with IC₅₀ values of 600 and 500 nM, respectively.

MRC-G-001 is a Genipin (HY-17389) derivative with an IC₅₀ of 117 μM against A549 cancer cells. MRC-G-001 inhibits the phosphorylation of EGFR, JAK1, and STAT3, and modulates epithelial-mesenchymal transition (EMT)-related protein expression, thereby attenuating cell migration and invasion. MRC-G-001 induces cell cycle arrest and cell apoptosis. MRC-G-001 can be used for the study of cancers such as non-small-cell lung cancer.

Tyk2-IN-18 (compound 86) is a potent tyrosine kinase 2 (Tyk2) inhibitor. Tyk2-IN-18 inhibits JAK2-JH2, with an IC₅₀ of ＜10 nM.

SYK/JAK-IN-1 is a dual Syk/Jak2 kinase inhibitor. SYK/JAK-IN-1 is applicable to cancer-related research.

Cucurbitacin I (Standard) is the analytical standard of Cucurbitacin I. This product is intended for research and analytical applications. Cucurbitacin I is a natural selective inhibitor of JAK2/STAT3, with potent anti-cancer activity.

MMT3-72 is a weak inhibitor of JAK1. MMT3-72 has superior efficacy and reduced p-STAT3 in DSS-induced colitis.

LS-104 (Tyrene CR-4) is a non-ATP-competitive kinase inhibitor against JAK2, Bcr-Abl and FLT3. LS-104 potently induces apoptosis in JAK2V617F-positive cells and inhibits JAK2 autophosphorylation and downstream signal transduction. LS-104 also inhibits proliferation and induces potent cytotoxic effects in FLT3 expressing leukemic cells. LS-104 is a hydroxystyryl-acrylonitrile compound, which is promising for research of myeloproliferative disorders and refractory/relapsed hematologic malignancies.

JAK2-IN-17 (compound 20) is a potent JAK2 allosteric inhibitor. JAK2-IN-17 inhibits full-length JAK2 and JAK2 V617F with IC₅₀s of 160 and 130 nM, respectively. JAK2-IN-17 covalently modifies Lys677 in the pseudokinase domain.

PRN-371 is a potent and selective JAK3 inhibitor. PRN371 effectively suppresses natural killer/T-cell lymphoma cell proliferation and induces apoptosis through abrogation of the JAK3-STAT signaling. PRN-371 exhibits antitumor activity and can be used for the research of cancer, such as hematological malignancies.

Jolkinolide B (Standard) is the analytical standard of Jolkinolide B (HY-N0732). This product is intended for research and analytical applications. Jolkinolide B is a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud with oral activity. Jolkinolide B downregulates XIAP, cIAP1, cIAP2, and phosphorylated Akt, upregulates Smac, activates caspase-3 and caspase-9, and inhibits NF-κB, TGFβ/smad3 and JAK/STAT3 pathways. Jolkinolide B exerts comprehensive biological effects including inducing cancer cell apoptosis, suppressing inflammatory responses, improving lung function, alleviating hepatic steatosis and eliminating intracellular Mycobacterium tuberculosis. Jolkinolide B can be used for the research of leukemia, histiocytic lymphoma, asthma, metabolic dysfunction-associated steatotic liver disease and tuberculosis.

JAK2-IN-14 is an orally active JAK2 inhibitor with an IC₅₀ of 2 nM. JAK2-IN-14 demonstrates 89.5-, 80.5-, and 51-fold selectivity over JAK1, JAK3, and TYK2, respectively. JAK2-IN-14 inhibits STAT5 signaling pathway. JAK2-IN-14 causes tumor cell cycle arrest and apoptosis. JAK2-IN-14 can used for the study of myeloproliferative neoplasms (MPNs).

oJak-989 is a selective JAK1 inhibitor with a K_i of 2.8 nM for JAK1, 110 nM for JAK3, and 31 nM for TYK2. oJak-989 is applicable to the research of inflammatory diseases.

LAS194046 is a selective pan-JAK inhibitor, with an IC₅₀ of 5.46 nM against JAK1, 0.4 nM against JAK2, and 2.07 nM against JAK3. LAS194046 reduces the levels of IL-8 and MMP-9. LAS194046 enhances the activation of glucocorticoid response elements by Fluticasone propionate. LAS194046 inhibits T2-type allergic pulmonary inflammation, allergen-induced airway inflammation, and late-phase asthmatic responses in rats. LAS194046 can be used in research related to non-T2 severe asthma, chronic obstructive pulmonary disease, and asthma.

JAK1-IN-17 (Compound 31) is a highly selective inhibitor of JAK1 with a K_i of 1.9 nM. JAK1-IN-17 exhibits a low whole blood shift, which allows maintaining good whole blood potency. JAK1-IN-17 is also a nitrile-containing analogue with consistent, yet weak reversible inhibition of CYP3A4 using a midazolam probe (IC₅₀ = 7.9 μM). JAK1-IN-17 can be studied in cancer research.

JAK3-IN-12 (compound 5k) is a highly potent JAK3 inhibitor with IC₅₀ values of 9.5 nM, 18 nM and 42 nM for JAK3, JAK1 and JAK2, respectively. JAK3-IN-12 can be used for researching rheumatoid arthritis.

JAK kinase-IN-1 (Example 1) is a JAK inhibitor. JAK kinase-IN-1 inhibits TYK2, JAK1, JAK2 and JAK3 with IC₅₀ values of 4.2 nM, 32 nM, 27 nM, 3473 nM respectively.

Antitumor agent-123 (Copmound 4d) effectively inhibits multiple kinase targets with anti-cancer effects, including JAK2, JAK3, HDAC1 and HDAC6, with IC₅₀ values of 34.6 and 2.6 μM for JAK2 and JAK3, respectively. Antitumor agent-123 exhibits moderate activity in solid tumor models.