anti-leukemic

Piribedil (Trivastan) is a dopamine D2 agonist, used in the treatment of Parkinson's disease.

ICCB280 was capable of inducing differentiation and apoptosis of ATRA-resistant patient blasts strongly signify that the activity of this compound can overcome resistance to other current therapies for AML with an unfavorable prognosis.

Coralyne chloride is a protoberberine with strong anticancer activity. It can be used to prepare Coralyne derivatives, a fluorescent DNA-based molecular rectifier built into DNA duplexes through site-specific insertion. It acts as a topoisomerase I toxic molecule, inducing topoisomerase I-mediated DNA cleavage.

ATH686 is an potent and selective Inhibitor of FLT3.

NL-1, a mitoNEET inhibitor, exhibits antileukemic effects.

KPT-251 is a selective nuclear export inhibitor.

nor-NOHA acetate (Nω-Hydroxy-nor-L-arginine acetate) is a reversible inhibitor of arginase with anti-leukemic activity, effective in treating endothelial dysfunction, immunosuppression, and metabolism regulation.

MI-192 is a selective HDAC2 and HDAC3 inhibitor with IC50 values of 30 nM and 16 nM, respectively. It exhibits greater selectivity for HDAC2/3 over other HDAC isomers and induces apoptosis in myeloid leukemic cells, indicating potential therapeutic use in leukemia and as an anti-stroke agent [1] [2].

LeuRS-IN-1 is an orally active and potent Mycobacterium tuberculosis leucyl-tRNA synthetase inhibitor with anti-leukemic and anti-malarial activity, inhibits M.tb LeuRS, inhibits HepG2 protein synthesis, and can be used in leukemia research.

Dihydro-5-azacytidine (DHAC) is an active nucleoside analog with anti-leukemic activity that inhibits cell growth and induces DNA hypomethylation.Dihydro-5-azacytidine is used in the study of leukemia and tumors.

LeuRS-IN-1 hydrochloride is an orally active and highly potent inhibitor of Mycobacterium tuberculosis leucyl-tRNA synthetase with anti-leukemic activity and anti-malarial activity, inhibits M.tb LeuRS, inhibits HepG2 protein synthesis, and can be used in the study of leukemia.

AKE-72 is a Pan-BCR-ABL inhibitor with anti-leukemic activity.AKE-72 inhibits the proliferation of Ba/F3 cells expressing natural BCR-ABL or its T315I mutant.

Eltanexor (ONO-7706) is an orally active exportin-1 (XPO1) inhibitor. It has effective anti-leukemic activity. Eltanexor inhibits XPO1-dependent nuclear export (EC50=60.9 nM) by directly targeting XPO1. Eltanexor causes caspase-dependent apoptosis in a panel of leukemic cell lines.

Resveratrol analog 1, an analog of Resveratrol, is a natural polyphenolic phytoalexin with antioxidant, anti-inflammatory, cardioprotective, and anti-cancer properties.

VTP50469 is a highly selective and orally active small molecule inhibitor of the Menin-MLL protein-protein interaction with potent anti-leukemic activity with a Ki of 104 pM.

ART838 is a dimeric pimeloyl urea compound notable for its potent anti-leukemic activity and favorable pharmacological properties. In vitro, ART-838 exhibits submicromolar inhibitory concentrations against all leukemia cell lines, demonstrating anti-leukemic efficacy 88 times greater than artemether. This compound remains in the body for extended periods and works synergistically with other anti-leukemic agents and novel kinase inhibitors to suppress leukemia cell growth. In immunodeficient NOD-SCID-IL2Rgnull (NSG) mice, ART-838 attains a plasma half-life longer than that of artemether, sustaining effective anti-leukemic concentrations for over 8 hours. Intermittent ART-838 treatment notably inhibited the growth of acute leukemia xenografts and primary grafts in NSG mice, surpassing the efficacy of artemether.

Denotivir (Vratizolin) is an orally active antiviral agent effective against herpes simplex virus (HSV) and varicella-zoster virus (VZV). It inhibits the proliferation of various cancer cells and possesses anti-leukemic properties. Additionally, Denotivir suppresses the production of TNF-α, IL-1, and IL-6, demonstrating immunosuppressive effects.

Purinostat is a selective inhibitor of HDACI/IIb with potential anti-leukemic properties. Its mesylate form, Purinostat mesylate, is effective at inhibiting the survival of Ph+ leukemic cells and CD34+ leukemic cells derived from CML patients. Purinostat mesylate targets HDACI/IIb, impacting several crucial factors for leukemia stem cell (LSC) survival, such as c-Myc, β-Catenin, E2f, Ezh2, Alox5, and mTOR. Additionally, Purinostat mesylate enhances glutamate metabolism in LSCs by increasing GLS1.

FLT3-IN-29 (Compound MY-10) is an FLT3 inhibitor with IC50 values of 6.5 nM and 10.3 nM for FLT3-ITD and FLT3-D835Y mutants, respectively. It induces cell cycle arrest at the G0/G1 phase and effectively triggers apoptosis (Apoptosis). Additionally, FLT3-IN-29 reduces reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), displaying anti-leukemic properties.

DP-15 acts as a degrader of GSPT1 and BRD4, with DC50 values of 5.25 nM and 0.48 nM, respectively. This compound exhibits antiproliferative activity in AML and NHL cells, showing IC50 values in the nanomolar range, induces G1 phase cell cycle arrest, and triggers apoptosis in MOLM13 cells. Additionally, DP-15 demonstrates anti-leukemic properties in the MOLM-13 xenograft mouse model. [Pink: ligand for target protein JQ-1 carboxylic acid; Black: linker; Blue: ligand for E3 ligaseCereblonThalidomide-5-OH]

Apoptosisinducer 36 (Compound 42) exhibits anti-leukemic activity by reducing leukemia stem cells (LSC) and inducing differentiation. It inhibits proliferation of AML cells by causing cell cycle arrest in the G1 phase, and induces PANoptosis, which includes apoptosis, pyroptosis, and necrosis.

ROTACMNK1degrader-1 is a selective MNK1 PROTAC degrader with a DC50 of 11.92 nM and a Dmax greater than 96% in MV4-11 cells. It significantly reduces p-eIF4E levels with an IC50 of 22.07 nM, induces apoptosis, and causes cell cycle arrest at the G1 phase. This compound exhibits potent antitumor activity, demonstrating strong anti-leukemic effects in MV4-11 xenograft mouse models with acceptable drug safety.

Leuxinostat, an inhibitor of HDAC, exhibits an IC50 of 30 nM against hHDAC6. It suppresses the proliferation of THP1, K562, U937, and MEK1 cells, while also inducing apoptosis in leukemia cells NB4 and MOLT-4. Additionally, Leuxinostat inhibits the expansion of hematopoietic stem cells and demonstrates anti-leukemic activity in a zebrafish model.

ARM165 is a heterobifunctional molecule that degrades the protein PIK3CG and inhibits the PI3Kγ-Akt signaling pathway, thereby exerting anti-leukemic effects. It is capable of suppressing the proliferation of AML cells, with an IC50 of less than 1 μM.