myeloproliferative

Fedratinib (TG-101348) (TG101348) is an ATP-competitive inhibitor of JAK2 (IC50: 3 nM) with significantly less potent activity against JAK3.

Bomedemstat ditosylate (IMG-7289 ditosylate) is an orally active lysine-specific demethylase 1 (LSD1) inhibitor with antitumor activity that potentiates the response to PD-1 inhibition in a homozygous model of SCLC, inhibits cancer cell proliferation, and induces apoptosis. Bomedemstat ditosylate can be used to study myeloproliferative neoplasms and myelofibrosis.

BTK-IN-24 is a Bruton's tyrosine kinase (BTK) inhibitor with potential anticancer activity, and it can be used in the study of myeloproliferative disorders.

JAK3-IN-7 is a potent and selective JAK3 inhibitor (IC50<0.01 μM) intended for the treatment of organ transplantation rejection, graft-versus-host reaction post-transplantation, autoimmune disorders, allergic diseases, and chronic myeloproliferative disorders.

BVB-808 is a selective Jak2 type 1 inhibitor. Janus kinases are critical components of signaling pathways that regulate hematopoiesis. Mutations of the non-receptor tyrosine kinase JAK2 are found in many BCR-ABL-negative myeloproliferative neoplasms. Preclinical results support that JAK2 inhibitors could show efficacy in treating chronic myeloproliferative neoplasms. JAK2 has also been postulated to play a role in BCR-ABL signal transduction. Therefore, inhibitors of JAK2 kinases are turning into therapeutic strategies for treatment of chronic myelogenous leukemia (CML).

Pipobroman (Vercyte) is an anti-cancer drug that probably acts as an alkylating agent. Pipobroman has well documented clinical activity in polycythemia vera (PV) and essential thrombocythemia (ET). Pipobroman allows, within 3 months, to attain a response in more than 90% of patients, without clinically relevant toxicities. The 10-years risk of thrombosis of patients treated with Pipobroman is about 15%, The anti-proliferative activity of Pipobroman on bone marrow megakaryocytes seems of particular value in lowering the occurrence of post-PV and post-ET MMM, whose risk is the lowest registered with available treatments. The 10-year risk of acute leukemia with Pipobroman is 5% in PVand 3% in ET, which is only slightly higher than that expected as a natural evolution of the disease. In conclusion, the use of Pipobroman is a definite alternative to hydroxyurea in patients with PV and ET at high risk of thrombosis.

Anagrelide (Xagrid) is a Platelet-reducing Agent. The mechanism of action of anagrelide is as a Phosphodiesterase 3 Inhibitor. The physiologic effect of anagrelide is by means of Decreased Platelet Production.

5MPN is an orally active and selective inhibitor of 6-phosphofructokinase-2-kinase (PFKFB4) that competitively inhibits the F6P binding site and inhibits the proliferation of myeloma cells, and can be used in the study of myeloproliferative neoplasms.

Fedratinib hydrochloride hydrate (SAR 302503 hydrochloride hydrate) is a potent, selective, ATP-competitive and orally active JAK2 inhibitor.

Bomedemstat (IMG-7289) is an orally active, irreversible inhibitor of lysine-specific demethylase 1 (LSD1) that exhibits antineoplastic activities in mouse models of myeloproliferative neoplasms (MPNs), and can be used for research on acute myelogenous leukemia (AML) and myelofibrosis (MF) [1].

Compound A8, known as JAK2-IN-9, is a selective JAK2 inhibitor with an IC50 of 5 nM. It effectively inhibits the phosphorylation of JAK2, STAT3, and STAT5, possesses metabolic stabilities, and induces apoptosis. This compound is utilized in the study of myeloproliferative neoplasms (MPNs) [1].

JAK2 JH2 binder-1 is a potent and selective JAK2 JH2 binder (Ki: 37.1 nM). JAK2 JH2 binder-1 has the potential to be used in the study of various myeloproliferative neoplasms.

Ropeginterferon alfa-2b (Ropeginterferon alfa-2b-njft), a monopegylated interferon-alpha (IFN-α), is used in the study of myeloproliferative neoplasms [1].

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.

ON044580 is an effective non-ATP-competitive inhibitor of JAK2, characterized as an α-benzoylstyrylbenzyl thioether. It exhibits IC50 values of 1.23 μM for wild type JAK2 and 1.09 μM for the V617F mutation. The compound inhibits JAK2 kinase activity by binding to the STAT-5 binding domain or the allosteric site of JAK2. In JAK2V617F-positive leukemia cells, ON044580 suppresses proliferation and induces apoptosis in Imatinib-resistant chronic myeloid leukemia (CML) cells. It also inhibits both wild type and T315I mutant forms of the BCR-ABL kinase. ON044580 is used in research for myeloproliferative diseases characterized by abnormal JAK STAT signaling.

ZT55, an orally active, highly-selective JAK2 inhibitor with an IC50 of 0.031 μM, inhibits proliferation of JAK2 V617F-expressing HEL cell lines, induces apoptosis and cycle arrest, and effectively inhibits HEL xenograft tumor growth in mice models. Suitable for studies on myeloproliferative neoplasms, polycythemia vera, and primary thrombocythemia, ZT55 offers promising applications.