mds

Ilorasertib (ABT-348) (ABT-348) is an ATP-competitive multitargeted kinase inhibitor, which inhibits Aurora A Aurora B Aurora C (IC50s: 120 nM 7 nM 1 nM). It also suppresses RET tyrosine kinase, PDGFRβ, and Flt1 (IC50s: 7 nM, 3 nM, and 32 nM).

Pevonedistat (MLN4924) is a potent and selective NEDD8 activating enzyme (NAE) inhibitor (IC50=4.7 nM) with therapeutic potential for myelodysplastic syndromes (MDS) and antitumor activity.

Laniquidar (R101933) is a third generation non-competitive inhibitor of P-glycoprotein (P-gp) (IC50: 0.51 μM) with limited oral bioavailability. It can also be used to modulate multidrug resistance transporters.

Pevonedistat hydrochloride (MLN4924 hydrochloride) is a selective and potent NEDD8 activating enzyme inhibitor (IC50: 4.7 nM) that induces apoptosis and cell cycle inhibition in cancer cells, and is used in the study of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Pelubiprofen has been used in the study of AML and MDS.)

Olutasidenib (FT-2102) is under the study in the treatment of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Olutasidenib is a highly effective, brain penetrant, and selective inhibitor of the mutant Isocitrate dehydrogenase 1 (IDH1) (IC50: 21.2 nM and 114 nM for IDH1- R132H and IDH1- R132C, respectively).

Ezatiostat hydrochloride (TLK199 HCl) is an effective inhibitor of glutathione S-transferase. Ezatiostat hydrochloride is a novel glutathione analog and the potential treatment of cytopenias. In addition, Ezatiostat hydrochloride has been revealed to selectively bind to and thus inhibit GSTP1-1.

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.

Ezatiostat (TER199(free base)) is a tripeptide analog of glutathione that can selectively inhibit GSTP1-1 catalytic activity.

Laniquidar TFA (R101933) is a novel orally available non-competitive P-glycoprotein (P-gp) inhibitor with an IC50 value of 0.51 μM.Laniquidar has limited bioavailability and can be used to modulate the multidrug resistance transporter.Laniquidar can be used for the study of AML and myelodysplastic syndrome (MDS). Laniquidar is used to study acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

Asunercept (APG101; CAN008), a soluble CD95-Fc fusion protein, selectively targets and binds to CD95L, effectively disrupting CD95 CD95L signaling. It is utilized in research for treating glioblastoma multiforme (GBM), myelodysplastic syndrome (MDS), and graft-versus-host disease (GvHD) [1] [2] [3].

Tomaralimab (OPN-305) is a humanized IgG4 monoclonal antibody targeting TLR2, used to study myelodysplastic syndromes (MDS).

UC-764864 is a selective UBE2N inhibitor that blocks E1-UBE2N thioester transfer, inhibits innate immune signaling and induces cytotoxic effects in MDS AML cell lines and primary cells. In addition, UC-764864 reduces the ubiquitination status of UBE2N and can be used to study leukemia.