anti-leukemic

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

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].

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.

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.

1. Oroxylin A (Baicalein 6-methyl ether) has various anti-tumor effects including apoptosis, cell cycle arrest, drug-resistant reversion. 2. Oroxylin A possesses abilities of inhibiting the ATRA-induced IL-6 production via modulation of LAP/LIP/CHOP in leukemia cell lines, which could providing a therapeutic strategy for RAS. 3. Oroxylin A inhibits UCP2s triggers the MPTP opening, and promotes the apoptosis in CaCo-2 cells; uncoupling protein 2 plays a key role in mitochondrial apoptotic pathway. 4. Oroxylin A inhibits N1ICD translocating to the nucleus and binding to epithelial-mesenchymal transition-related transcription factor Snail, thus suppressing the invasion and migration of MCF-7 cells. 5. Oroxylin A improves the sensitivity of K562/ADM cells by increasing apoptosis in leukemic cells and decreasing the expression of CXCR4 and PI3K/Akt/NF-κB pathway, and probably served as a most promising agent for CML treatment.

Toddaculine may be beneficial for the prevention and treatment of osteoporosis, it can not only inhibit the differentiation of osteoclasts via activation of the NF-κB, ERK 1 2, and p38 MAPK signaling pathways, but can induce differentiation and mineralization of osteoblasts by regulating differentiation factors. Toddaculine also may serve as a pharmacological prototype for the development of novel anti-leukemic agents, it displays a dual effect as a cell differentiating agent and apoptosis inducer in U-937 cells.

AKI603 is a novel small molecule inhibitor of Aurora kinase A (AurA)(IC50 = 12.3 nM). AKI603 is developed to overcome resistance mediated by BCR-ABL-T315I mutation. AKI603 exhibits strong anti-proliferative activity in leukemic cells[1][2].

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.

1. Crebanine iv 5mg/kg can eonvert BaCl_2-induced arrhythmia into sinus rhythm in rats, and can significantly increase the tolerant dose of aconitine to produce ventrieular fibrillation(VF) and cardiac arrest (CA) in rata. 2. Crebanine can also decrease t

THZ-P1-2 is a selective and potent PI5P4K inhibitor with anti-leukemic activity that acts by disrupting mitochondrial homeostasis and autophagy.THZ-P1-2 induces cell death and mitochondrial damage, and can be used in the study of leukemias.

Casein Kinase inhibitor A86 is a highly effective and orally bioavailable inhibitor of casein kinase 1α (CK1α) and also inhibits CDK7 (TFIIH) and CDK9 (P-TEFb). It induces apoptosis in leukemia cells, exhibiting substantial anti-leukemic effects.

SJ 11646, a potent lymphocyte-specific protein tyrosine kinase (LCK) Degrader (PROTAC) with a DC50 of 0.00838 pM, utilizes Dasatinib as the LCK ligand and incorporates a phenyl glutarimide-based cereblon binder. Demonstrating cytotoxicity in both LCK-activated T cell acute lymphoblastic leukemia (T-ALL) cell lines and primary leukemia samples in vitro, SJ 11646 also exhibits anti-leukemic efficacy in vivo within patient-derived xenograft models of T-ALL.

BCR-ABL-IN-5 is a Bcr-Abl (Breakpoint cluster region-Abelson) kinase inhibitor that acts on Bcr-AblWT (IC50: 0.014 μM) and Bcr-AblT3151 (IC50: 0.45 μM) and exhibits some anti-proliferative effects on leukemic cells. effect.

PLM-101 is an anticancer compound orally active against acute myeloid leukemia by targeting FLT3 and RET. It impedes RET function, promoting autophagic breakdown of FLT3, and suppresses the PI3K and Ras/ERK pathways, contributing to its anti-leukemic effects. The compound's antitumor efficacy is demonstrated in both a mouse MV4-11 flank xenograft model (doses of 3 and 10 mg/kg; po) and an allogeneic xenograft mouse model (dose of 40 mg/kg; po) [1].

Grisnilimab setaritox (WT1-RTA), an anti-CD7 antihuman T cell antibody linked to ricin A chain (RTA), exhibits in vitro cytotoxicity against CEM (T-lymphoblastic leukemia) cells with an ID 50 of 53 pM. The 30-kDa RTA component disrupts the function of 60S ribosomal subunits. Additionally, Grisnilimab setaritox has demonstrated efficacy in ameliorating leukemic meningitis in a rhesus monkey model [1].

RUNX1 ETO tetramerization-IN-1 is a small-molecule inhibitor targeting NHR2 of RUNX1 ETO, effectively inhibiting tetramerization with an EC50 value of 0.25 μM. This compound restores gene expression down-regulated by RUNX1 ETO and demonstrates anti-leukemic activity by inhibiting proliferation of RUNX1 ETO-dependent SKNO-1 cells and reducing tumor growth in a mouse model [1] [2] [3].

AS-85, a potent inhibitor of ASH1L histone methyltransferase (IC50 = 0.6 μM), exhibits anti-leukemic activity by strongly binding to the ASH1L SET domain (Kd = 0.78 μM).

DW71177 is a bd1-selective and potent BET inhibitor with potent anti-leukemic activity for the study of leukemia.

Lusvertikimab (OSE-127), a humanized IL7R monoclonal antibody, does not get internalized by target cells and inhibits IL7R heterodimerization along with subsequent downstream signaling. It demonstrates anti-leukemic properties and holds potential for research in B cell precursor acute lymphoblastic leukemia (BCP-ALL) [1].

CWI1-2 is a potent IGF2BP2 inhibitor that inhibits its interaction with M6A-modified target transcripts by binding IGF2BP2. CWI1-2 has anti-leukemic activity and can induce apoptosis and differentiation.

AS-99 is a first-in-class, potent, and selective inhibitor of the ASH1L histone methyltransferase, displaying anti-leukemic activity with an IC50 of 0.79 µM and a Kd of 0.89 µM. It inhibits cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and effectively reduces leukemia burden [in vivo].

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.

AC-4-130, a powerful inhibitor of the SH2 domain of STAT5, effectively hinders STAT5 activation, dimerization, nuclear translocation, and transcription of genes reliant on STAT5. This compound directly binds to STAT5, ultimately leading to cell cycle arrest and apoptosis in FLT3-ITD-driven leukemic cells. AC-4-130 exhibits notable anti-cancer properties and effectively suppresses abnormal STAT5 activity in acute myeloid leukemia (AML), making it a promising therapeutic option [1].

AS-99 is a first-in-class, potent, and selective ASH1L histone methyltransferase inhibitor (IC50= 0.79 μM, Kd= 0.89 μM) with anti-leukemic activity, blocking cell proliferation, inducing apoptosis and differentiation, downregulating MLL fusion target genes, and reducing the leukemia burden in vivo[1].

AS-99 TFA is a first-in-class, potent, and selective ASH1L histone methyltransferase inhibitor (IC50= 0.79 μM, Kd= 0.89 μM) with anti-leukemic activity. It blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo[1].

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.

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

Deoxyharringtonine, an alkaloid extracted from the Cephalotaxus genus, exhibits significant anti-leukemic properties [1].