leukemic

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

GSK-690 is a selective and potent inhibitor of lysine demethylase 1 (LSD 1), which induces differentiation of leukemic stem cells in acute myeloid leukemia (AML), and can be used in the study of leukemias.

TCS-PIM-1-4a (SMI-4a), a Pim inhibitor, blocks mTORC1 activity through activation of AMPK and kills a wide range of both myeloid and lymphoid cell lines (IC50=0.8-40 μM).

BETd-260, a PROTAC linked by a Cereblon ligand and a BET ligand, has an inhibitory effect on BRD4 protein in leukemic cell lines.

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].

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.

HM43239 is an orally active and selective FLT3 inhibitor with IC 50 s of 1.1 nM, 1.8 nM and 1.0 nM for FLT3 WT, FLT3 internal tandem duplication (ITD) and FLT3 D835Y kinases, respectively. HM43239 directly inhibits the kinase activity of FLT3 as a reversible Type I inhibitor and effectively modulates downstream p-STAT5 and p-ERK. HM43239 also demonstrated inhibition of SYK, JAK1 2 and TAK1. HM43239 inhibits the proliferation and induces the apoptosis of leukemic cells [1] [2] [3].

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.

Unesbulin (PTC596) is an orally active, selective inhibitor of B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1).

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.

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].

Eucalyptol, a natural monoterpenoid and cyclic ether found in eucalyptus species, effectively controls excessive airway mucus secretion and asthma by inhibiting pro-inflammatory cytokines. It serves as an efficacious treatment for non-purulent sinusitis, reducing inflammation and pain when applied topically, and demonstrating leukemic cell-killing capabilities in vitro.

Rilmenidine Phosphate is a selective I(1) imidazoline receptor agonist, used to treat hypertension.

ZG36, a human Caseinolytic protease P (ClpP) agonist, non-selectively degrades respiratory chain complexes and reduces mitochondrial DNA, causing mitochondrial dysfunction and inducing leukemic cell death. Additionally, it inhibits the development of acute myeloid leukemia in a xenograft mouse model [1].

Cytarabine triphosphate (Ara-CTP), a competitive inhibitor of DNA synthesis and an active metabolite of Cytarabine, exhibits predictive potential for leukemic blasts' chemosensitivity to Cytarabine through intracellular levels.

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.

N-Myristoyl-Lys-Arg-Thr-Leu-Arg is a protein kinase C (PKC) inhibitor (IC50 = 75 μM) that effectively inhibits IL-2 receptor induction and IL-2 production in the human leukemic cell line Jurkat [1].

HDAC8-IN-3 (compound P19) is a highly potent HDAC8 inhibitor with an IC50 value of 9.3 μM, inducing thermal stabilization, cytotoxicity, and apoptosis specifically in leukemic cell lines [1].

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.

Quizartinib, also know as AC220 and AC010220, is an orally available FLT3 / STK1 inhibitor with potential antineoplastic activity. Class III receptor tyrosine kinase inhibitor AC220 selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs), resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis. Mutations in FLT3, resulting in constitutive activation, are the most frequent genetic alterations in acute myeloid leukemia (AML) and occur in approximately one-third of AML cases.

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.

ZLD115 (compound 44), a derivative of FB23, functions as an inhibitor of the Fat Mass and Obesity-associated Protein (FTO) and demonstrates antiproliferative properties as an antileukemic agent against leukemic cell lines [1].

Forodesine (BCX-1777) is an orally active and potent purine nucleoside phosphorylase (PNP) inhibitor, a new purine nucleoside analog, inhibitor of human lymphocyte proliferation, induces apoptosis in leukemic cells by increasing dGTP levels, and may be useful in the study of cutaneous T-cell lymphomas.

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.

2'-Deoxy-2-iodoadenosine is a purine nucleoside analog with potential antimicrobial, antioxidant and anti-leukemic activities.

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].

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).

Forodesine hydrochloride (BCX-1777 hydrochloride), a potent inhibitor of human lymphocyte proliferation, effectively induces apoptosis in leukemic cells by elevating dGTP levels. This compound is an orally active, highly potent purine nucleoside phosphorylase (PNP) inhibitor, demonstrating IC50 values between 0.48 to 1.57 nM across human, mouse, rat, monkey, and dog PNP.

(2S)-4'-Hydroxy-7-methoxyflavan, a flavan, exhibited substantial cytotoxicity against human leukemic Molt 4 cells [1].

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

Cis-3,4',5-Trimethoxy-3'-hydroxystilbene, a stilbene derivative, induces apoptosis through the mitochondrial release of cytochrome c and suppresses tubulin polymerization. It is also noted for its application in leukemic research [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.

HXR9 is a cell-permeable peptide that acts as a competitive antagonist of the HOX PBX interaction, effectively inhibiting the binding between HOX proteins and the transcription factor PBX in paralogue groups 1 to 8. HXR9 selectively impairs cell proliferation and induces apoptosis in cells with high expression of the HOXA PBX3 genes (e.g., MLL-rearranged leukemic cells).

Deacylcortivazol (DAC) is a potent glucocorticoid. When incubated with glucocorticoid-resistant mutants derived from the glucocorticoid-sensitive human leukemic cell line CEM-C7, DAC caused significant growth inhibition. The cytotoxicity of DAC at concent

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.

Alisertib sodium (MLN 8237) is a potent and specific inhibitor (IC50 = 1.2 nM) of Aurora A kinase, an enzyme involved in cell division. By binding to Aurora A kinase, Alisertib sodium disrupts the formation of the mitotic spindle, causing abnormal cell division. At the molecular level, it acts on the AKT mTOR AMPK p38 pathway, leading to the induction of apoptosis and autophagy in leukemic cells, and exhibits significant antitumor activity.

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].

KU-0058948 is a poly (ADP-ribose) polymerase (PARP) inhibitor that induces cell cycle arrest and apoptosis of primary myeloid leukemic cells and myeloid leukemic cell lines in vitro.

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].

Cytarabine triphosphate (Ara-CTP) trisodium, an active metabolite of Cytarabine, is a competitive inhibitor of DNA synthesis. Intracellular Cytarabine triphosphate trisodium levels can predict the chemosensitivity of leukemic blasts to Cytarabine [1].

1,4-Anthraquinone is an anticancer drug that blocks nucleoside transport, inhibits macromolecule synthesis, induces DNA fragmentation, and decreases the growth and viability of L1210 leukemic cells in the same nanomolar range as daunorubicin in vitro.1,4-

YIGSR is a peptide that inhibits tumor growth and metastasis of leukemic cells [1].

Orpinolide, a withanolide analog, exhibits anti-leukemic properties. It disrupts the homeostasis of the Golgi apparatus, a process associated with the signaling of phosphatidylinositol 4-phosphate at the interface of the endoplasmic reticulum and Golgi membranes.

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].