jak2 in 6

JAK2-IN-6, a polysubstituted aminothiazole derivative, is a potent and selective inhibitor of JAK2 (ic50 at 22.86 μg mL). Jak2-in-6 inhibits the activity of JAK2 enzymes by interfering with Jak2-related signaling pathways, thereby producing therapeutic effects on the specific disease IN which JAK2 is dysregulated, and does not show activity on JAK1 and JAK3. JAK2 is a protein involved in signaling pathways that regulate cell growth and division. Abnormal activation of JAK2 has been linked to a variety of diseases, including some types of cancer and inflammatory diseases. JAK2-IN-6 has antiproliferative activity against cancer cells.

Pacritinib (SB1518) (SB1518) is an effective and specific inhibitor of JAK2 and FLT3 (IC50: 23 22 nM, in cell-free assays).

JAK2-IN-11 (Example 6) is a JAK2 kinase inhibitor with potent antitumor activity, exhibiting an IC50 of ≤10 nM against JH2 BIND WT V617F. This compound effectively suppresses tumor growth.

α7 nAchR-JAK2-STAT3 agonist 1 is a potent inhibitor of the α7 nAchR-JAK2-STAT3 pathway that acts on nitric oxide (NO) (IC50: 0.32 μM). It has demonstrated positive effects on iNOS, IL-1β, and IL-1β in murine macrophages RAW264.7, and inhibited the expression of iNOS, IL-1β, and IL-6 in mouse macrophages. Additionally, α7 nAchR-JAK2-STAT3 agonist 1 suppressed LPS-induced NO release, NF-κB activation, and cytokine production, making it useful for studying sepsis.

JAK1 TYK2-IN-3 is a selective, potent, orally active dual inhibitor of TYK2 (IC50: 6 nM) and JAK1 (IC50: 37 nM), with selective action on JAK2 (IC50: 140 nM) and JAK3 (IC50: 362 nM). It regulates the expression of TYK2 JAK1-related genes and formation of Th1, Th2, and Th17 cells to exert anti-inflammatory activity.

Pacritinib hydrochloride is a potent inhibitor of wild-type JAK2 (IC50: 23 nM) and the JAK2V617F mutant (IC50: 19 nM), and can be used in the study of acute myeloid leukaemia (AML) and myelofibrosis (MF).

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. ).

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].

Antiproliferative Agent-34 (Compound A14), a multitarget kinase inhibitor, demonstrates IC50 values of 177 nM for EGFR L858R T790M and 1567 nM for EGFR WT. Additionally, it inhibits JAK2, ROS1, FLT3, FLT4, and PDGFRα with respective IC50s of 30.93 nM, 106.90 nM, 108.00 nM, 226.60 nM, and 42.53 nM. In normoxic conditions, it suppresses the proliferation of H1975 and HCC827 cells with IC50 values below 40 nM, while under hypoxic conditions, its potency increases 4-6 fold, yielding IC50 values less than 10 nM [1].

Pacritinib (SB1518) citrate effectively inhibits wild-type JAK2 (IC 50 =23 nM) and the JAK2 V617F mutant (IC 50 =19 nM). It also targets FLT3 (IC 50 =22 nM) and the FLT3 D835Y mutant (IC 50 =6 nM). This compound is utilized in the study of acute myeloid leukemia (AML) and myelofibrosis (MF) [1] [2] [3].

Pacritinib-d8 is a deuterated compound of Pacritinib. Pacritinib has a CAS number of 937272-79-2. Pacritinib (SB1518) is an effective and specific inhibitor of JAK2 and FLT3 (IC50: 23 22 nM, in cell-free assays).

(R)-Reticuline is a natural alkaloid that can be catalyzed by the microsomal P-450 system in plants and animals for conversion to Salutaridine, which is involved in endogenous morphine synthesis. The isomer of (R)-Reticuline is Reticuline. Reticuline inhibits the JAK2 STAT3 and NF-κB signaling pathways, and also inhibits the mRNA expression of TNF-α and IL-6, with anti-inflammatory effects.