Jakafi (ruxolitinib)

Furthermore, 5,7,4'-trimethoxyflavone was verified to bind to LRPPRC, STAT3, and CDK1, dissociating LRPPRC-JAK2-STAT3 and JAK2-STAT3-CDK1 interaction, leading to impaired tumorigenesis in 4-Nitroquinoline N-oxide induced ESCC mouse models and suppressed tumor growth in ESCC patient derived xenograft mouse models. In summary, this study suggests regulation of m6A modification by LRPPRC, and identifies a novel triplex target compound, suggesting that targeting LRPPRC-mediated JAK2/STAT3/MYC axis may overcome JAK2/STAT3/MYC dependent tumor therapeutic dilemma.

P2, N=230, Not yet recruiting, Ryvu Therapeutics SA

P2, N=74, Terminated, Incyte Corporation | Completed --> Terminated; A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this decision.

P1, N=9, Active, not recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

P2, N=120, Not yet recruiting, Incyte Corporation

In addition, WU derivatives effectively downregulated CXCR3 and T-bet in primary murine T cells. In summary, we have generated novel JAK inhibitors that could serve as alternatives to baricitinib or ruxolitinib.

Later, the patient received fedratinib, a relatively JAK2-selective inhibitor, without relapse of histoplasmosis. Although uncommon, a high index of suspicion for opportunistic IFIs is needed in patients receiving JAK inhibitors. Furthermore, the paucity of data regarding the optimal management of IFIs in patients treated with JAK inhibitors underscore the need for well-designed studies to evaluate the epidemiology, pathobiology, early diagnosis, and multimodal therapy of IFIs in patients with hematological malignancies receiving targeted therapies.

This case report demonstrates the feasibility and role of combination pre-clinical high throughput screening to aid decision making in high-risk leukaemia. It also demonstrates the role a JAK1/2 inhibitor can have in the palliative setting in select patients with AML.

P1/2, N=206, Recruiting, Incyte Corporation | N=100 --> 206 | Trial completion date: Apr 2024 --> Jun 2026 | Trial primary completion date: Apr 2024 --> Nov 2025

Furthermore, tailoring treatment with currently available JAK inhibitors (such as ruxolitinib or fedratinib) does not modify the natural history of the disease and has important limitations, including cytopenias...Specifically, we tested the JAK1/2 inhibitor, ruxolitinib; the NF-κB inhibitor via IKKα/β, BMS-345541; both inhibitors in combination; or a dual inhibitor of both pathways (JAK2/IRAK1), pacritinib...Additionally, combined treatment reduced both COL1A1 and IL-6 production in an in vitro model mimicking JAK2-driven fibrosis. In conclusion, NF-κB inhibition reduces, in vitro and in vivo, disease burden and BM fibrosis, which could provide benefits in myelofibrosis patients.

For patients with multiple myeloma, treatment with RUX and MP is effective and well tolerated, and LEN can be used to extend the benefit of this RUX-based treatment.

P2, N=23, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Feb 2024 --> Aug 2024

Recent years have seen the emergence of novel therapeutic agents, notably ruxolitinib and fedratinib, which target the Janus kinases (JAK) pathway. Due to its mechanism of action, MMB represents a valuable therapeutic option in MF, addressing the clinical challenge of anemia and potentially improving outcomes for patients with hematologic malignancies. Ongoing research explores MMB's potential in acute myeloid leukemia and combination therapies.

P1/2, N=47, Recruiting, Ohio State University Comprehensive Cancer Center | Suspended --> Recruiting

P2, N=33, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Mar 2024 --> Sep 2024

P1, N=60, Active, not recruiting, Case Comprehensive Cancer Center | Trial primary completion date: Dec 2023 --> Jun 2024

P1, N=24, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting | N=12 --> 24 | Trial primary completion date: Aug 2024 --> Apr 2024

In STAT1-GOF patients, T lymphocyte apoptosis is increased, and T lymphopenia may determine higher risk of severe infections. The JAKinib target therapy should be evaluated to treat severe chronic candidiasis and lymphopenia, and to downregulate the IFNs in patients with autoinflammatory or autoimmune manifestations.

By examining the keywords, we found that the diagnosis and typing of true erythrocytosis, the use of ruxolitinib, and the tyrosine kinase JAK2 are the research hotspots in the field; genetic and molecular research in the field of true erythrocytosis is a cutting-edge topic in the field; and risk factors for true erythrocytosis is a cutting-edge hotspot issue in the field...Currently, research should focus on increasing global multicenter collaborative research in diagnosis and treatment to develop scientifically recognized diagnostic and treatment protocols and new clinical drug research. Our proposed model of global innovation collaboration will provide strong support for future research.

In this report, we describe the case of a 28-year-old female with bilateral breast cancer in the setting of a BRCA1 mutation, who presented to dermatology with an eczematous reaction, ultimately diagnosed as a cutaneous immune-related adverse event (cirAE) secondary to an immune checkpoint inhibitor (ICI), pembrolizumab. To our knowledge, this is the first case report in the literature discussing use of a topical JAK inhibitor, ruxolitinib, in the treatment of topical steroid-refractory cirAEs. Furthermore, as topical JAK inhibitors are thought to not carry the risks of systemic JAK inhibitors, including malignancy, ruxolitinib cream is a promising therapeutic option for this challenging patient population.

P1/2, N=12, Completed, Wake Forest University Health Sciences | Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> Feb 2024

P3, N=330, Recruiting, AbbVie | Trial completion date: Jan 2031 --> Nov 2031

P1, N=49, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

P2, N=30, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=66, Not yet recruiting, ReAlta Life Sciences, Inc.

While corticosteroids were ineffective in all treated JAK-STAT-mutated patients, ruxolitinib showed positive hematological responses including in STAT5A-mutated patients. These findings emphasize the usefulness of NGS for the workup of tyrosine kinase fusion-negative HE/HES patients and support the use of JAK inhibitors in this setting. Updated classifications could consider patients with JAK-STAT mutations and eosinophilia as a new "gene mutated-entity" that could be differentiated from CEL, NOS, and idiopathic HES.

TN-MF is invariably associated with significantly decreased survival and more aggressive clinical behavior with higher rates of leukemic transformation and shorter duration of response to ruxolitinib. Mutations impacting RNA splicing, epigenetic modification and signaling (SRSF2, SETBP1, IDH2, CBL, and GNAS) are more common in TN-MF, which likely drive its aggressive course and may account for suboptimal responses to JAK inhibition.

P1, N=120, Recruiting, Mayo Clinic | Trial completion date: Dec 2024 --> Apr 2032 | Trial primary completion date: Dec 2024 --> Dec 2028

P=N/A, N=319, Completed, European Society for Blood and Marrow Transplantation | Active, not recruiting --> Completed

P1/2, N=1, Recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

Additionally, in glutamate-induced excitotoxicity astrocytes, ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3, thereby reducing glutamate-induced neurotoxicity, calcium influx, oxidative stress, and cell apoptosis, and increasing the complexity of dendritic branching. Collectively, these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes, reduces neurotoxicity, and effectively alleviates inflammatory and immune responses after spinal cord injury, thereby promoting functional recovery after spinal cord injury.

P2, N=33, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=25, Recruiting, University of Washington | Trial completion date: Nov 2024 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2026

No new or unexpected safety signals were identified. Overall, momelotinib provides spleen, symptom, and anemia benefits to JAK inhibitor-naive patients with myelofibrosis regardless of baseline hemoglobin level, and greater anemia-related benefits vs. ruxolitinib in patients with hemoglobin <12 g/dL.

P1, N=31, Active, not recruiting, Brian Druker | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=12, Recruiting, Incyte Corporation

P3, N=430, Active, not recruiting, Constellation Pharmaceuticals | Trial completion date: Dec 2026 --> Dec 2027

Pro-inflammatory cytokines and iron parameters were longitudinally assessed, which revealed suppression of interleukin-6 and interferon-gamma in a dose-dependent manner across a subset of patients. These results suggest that combination therapy targeting both JAK2 and NFκB may hold clinical merit for MPN patients.

P1/2, N=216, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

P2, N=60, Recruiting, Massachusetts General Hospital | Trial completion date: Jul 2023 --> Dec 2024 | Trial primary completion date: Jul 2023 --> Dec 2024

P1, N=49, Not yet recruiting, Washington University School of Medicine | Phase classification: P2 --> P1

P3, N=430, Active, not recruiting, Constellation Pharmaceuticals | Trial completion date: Apr 2027 --> Dec 2026