leukaemia

STM2457 is an inhibitor of the RNA methyltransferase METTL3 (IC50=16.9 nM) with selective and oral activity.STM2457 can be used in acute myeloid leukemia (AML) studies.

1. Chelidonine (Stylophorin) isolated from Chelidonium majus efficiently induced apoptosis in HeLa cells through possible alteration of p38-p53 and AKT/PI3 kinase signalling pathways. 2. Chelidonine is a promising model compound for overcoming MDR and for enhancing cytotoxicity of chemotherapeutics, especially against leukaemia cells, its efficacy needs to be confirmed in animal models. 3. Chelidonine may be a potential therapeutic agent against metastasis of invasive human cancer cells, exhibits antimigratory and antiinvasive effects in MDA-MB-231 cells, by suppressing COL-induced integrin signaling, through inhibiting the formation of the IPP complex and subsequent downregulation of IPP downstream signaling molecules, such as Akt and ERK1/2.

Tubulin polymerization-IN-43 is an inhibitor of tubulin polymerisation.Tubulin polymerization-IN-43 has multiple effects, disrupting the cellular microtubule network by targeting the colchicine locus and promoting cell cycle arrest and apoptosis in leukaemia cells. Tubulin polymerisation-IN-43 has multiple effects, promoting leukaemia cell cycle arrest in G2/M phase and apoptosis by targeting Colchicine sites to disrupt the cellular microtubule network.

IDH2R140Q-IN-2 is an orally active and potent IDH2R140Q inhibitor with an IC50 of 29 nM.IDH2R140Q-IN-2 possesses potential antitumour activity, reducing D2HG production in TF-1 cell lines carrying the IDH2R140Q mutation (IC50 of 10 nM) and inhibiting tumour tissue D2HG levels.IDH2R140Q-IN-2 is suitable for the study of acute myeloid leukaemia (AML).

OTUB1/USP8-IN-1 HCL is a potent dual inhibitor of OTUB1 and USP8 with potential antitumour activity, inhibiting both OTUB1 and USP8. OTUB1/USP8-IN-1 may be used in the study of leukaemia.

Senexin C is a novel orally active and specific CDK8/19 inhibitor with potential anticancer activity.Senexin C is more metabolically stable and potent than Senexin B. Senexin C inhibits the growth of MV4-11 leukaemia cells.

MI-192 is a selective HDAC2 and HDAC3 inhibitor with IC 50 s of 30 nM and 16 nM, respectively. MI-192 is more selective for HDAC2/3 than other HDAC isomers.MI-192 induces myeloid leukaemic cells apoptosis. MI-192 has potential use in leukaemia and anti-stroke [1] [2].

Vamotinib (PF-114) is an orally active and specific tyrosine kinase inhibitor with antiproliferative and antitumour activity.Vamotinib inhibits the phosphorylation of BCR/ABL and BCR/ABL-T315I, which promotes apoptosis. Vamotinib is used to study drug-resistant Philadelphia chromosome-positive (Ph+) leukaemia and Alzheimer's disease.

Ethacrynic acid (Edecrin) is a nonsulfonamide loop diuretic that inhibits the activity of the Na+/K+/2Cl- cotransporter NKCC2 in the thick ascending limb of the loop of Henle. It also inhibits glutathione S-transferase and Wnt signalling, producing cytotoxicity in chronic lymphocytic leukaemia cells and other tumour cells.

Mitoxantrone (mitozantrone) is an anthracenedione antibiotic with antineoplastic activity. Mitoxantrone intercalates into and crosslinks DNA, thereby disrupting DNA and RNA replication. This agent also binds to topoisomerase II, resulting in DNA strand breaks and inhibition of DNA repair. Mitoxantrone is less cardiotoxic compared to doxorubicin.

OICR-9429 is a potent antagonist of the interaction that WDR5 effect with peptide regions of MLL and Histone 3. It reduces the viability of acute myeloid leukemia cells in vitro.

Carboxyamidotriazole Orotate (L-651582 Orotate) is a cytostatic inhibitor of non-voltage-operated calcium channels and calcium channel-mediated signaling pathways. Carboxyamidotriazole Orotate (L-651582 Orotate) is the orotate salt form of Carboxyamidotriazole (CAI), an orally bioavailable signal transduction inhibitor that in vitro has been shown to possess antileukaemic activities. Carboxyamidotriazole Orotate shows anti-tumor, anti-inflammatory, and antiangiogenic effects.

Ofatumumab is a fully human monoclonal antibody to CD20 which appears to inhibit early-stage B lymphocyte activation

1alpha-Hydroxy VD4 can effectively induce the differentiation of monoblastic leukaemia U937, P39/TSU, and P31/FUJ cells.

Isomitraphylline and pteropodine are the most suitable for standardization of medical cat's claw preparations. Isomitraphylline can inhibit proliferation of acute lymphoblastic leukaemia cells.

Loliolid is a germination inhibitor, and a repellent for ants (Atta cephalotes).It has cytostatic activity against carcnoma and leukaemia cells.

Daunomycinone (NSC-109351) is a glycan of daunomycin, which belongs to the antibiotic class and is a representative glycan of tumour-inhibiting anthracyclines, used in the treatment of cancer and leukaemia.

Purinostat mesylate is a selective HDAC inhibitor. purinostat mesylate inhibits type I and type IIb HDACs (IC50: 0.81-11.5 nM). purinostat mesylate affects the cell cycle of LAMA84 and 188 BL-2 cells and induces apoptosis, showing a strong anti-leukaemic effect in vivo. purinostat mesylate has been used to study lymphocytic leukaemia. Purinostat mesylate can be used to study lymphocytic leukaemia.

XY153 (compound 8l) is a BD2 selective BET inhibitor that selectively binds BRD4 BD2. XY153 binds BRD4 BD2 (IC50: 0.79 nM), BRD3 BD2 (IC50: 5.31 nM) and BRD2 BD2 (IC50: 5.09 nM). XY153 can be used to study acute myeloid leukaemia and cancer.

Enocitabine is a nucleoside analog. Enocitabine inhibits the replication of human cytomegalovirus(HCMV) and it also has antileukemic and antiviral activities. Enocitabine is also a potent DNA replication inhibitor and a DNA chain terminator.

MAX-40279 hemiadipate is a potent, dual FLT3 kinase and FGFR kinase inhibitor. MAX-40279 hemiadipate has shown investigational potential in acute myeloid leukaemia (AML).

PI3K-IN-35 (Compound 6l) is a highly selective inhibitor of PI3K, acting on PI3K-α (IC50: 13.98 μM), PI3K-β (IC50: 7.22 μM) and PI3K-δ (IC50: 10.94 μM). PI3K-IN-35 blocks the cell cycle in G2/M phase and induces apoptosis. PI3K-IN-35 can be used to study leukaemia.

IST5-002 is a potent inhibitor of Stat5a/b and selectively inhibits the transcriptional activity of Stat5a/b with IC50 values of 1.5 μM and 3.5 μM for Stat5a and Stat5b, respectively. IST5-002 can be used to study prostate cancer and chronic granulocytic leukaemia (CML).

VEGFR-2-IN-26 (compound 5h) is a potent inhibitor of VEGFR-2 (IC50: 15.5 nM).VEGFR-2-IN-26 exhibits good anti-proliferative effects on leukaemia, CNS, non-small lung, ovarian, renal, prostate and breast cancer cells.

Nelarabine (GW 506U78) is a purine nucleoside analog and DNA synthesis inhibitor with IC50 from 0.067-2.15 μM in tumor cells.

MAX-40279 hemifumarate is a potent dual inhibitor of FLT3 kinase and FGFR kinase. MAX-40279 hemifumarate has shown investigational potential in acute myeloid leukaemia (AML).

Rilmenidine hemifumarate (S-3341 hemifumarate) is a novel, orally active and selective I1 imidazoline receptor and α2-adrenoceptor agonist that induces autophagy, regulates the proliferation of leukaemia cells, stimulates the pro-apoptotic protein Bax, and induces autophagy in human leukaemia K5 cells. induces disruption of the mitochondrial pathway and apoptosis in human leukaemia K562 cells.

Evocarpine shows antimycobacterial, and vasorelaxant effects, it can inhibit Ca2+ influx through voltage-dependent calcium channels.

XX-650-23 is a small molecule CREB inhibitor that blocks the critical interaction between CREB and its required coactivator, CBP (CREB-binding protein), inducing apoptosis and cell cycle arrest in AML cells, and can be used in the study of acute myelogenous leukaemia (AML).

Pacritinib hydrochloride is a potent inhibitor of wild-type JAK2 (IC50: 23 nM) and the JAK2V617F mutant (IC50: 19 nM). Pacritinib hydrochloride can be used in the study of acute myeloid leukaemia (AML) and myelofibrosis (MF).

Licochalcone C (LICOCHALCONEC) has potent antioxidant properties and inhibition of bacterial growth and cellular respiration. It has cardioprotection effect, via antioxidant, anti-inflammatory, and anti-apoptotic activities. Licochalcone C exhibit inhibitory activity with cytotoxicity in a rat basophilic leukaemia cell line, RBL-2H3. Licochalcone C induces apoptosis via B-cell lymphoma 2 family proteins in T24 cells, it may be a potential adjuvant therapeutic agent for bladder cancer.

MC2652 (compound 1a) is a potent LSD1 inhibitor that shows high inhibitory effects in leukaemia cells MV4-11 and NB4. MC2652 has antiproliferative activity against LNCaP cells of prostate cancer [1].

Spleen tyrosine kinase (Syk) inhibitor (pIC50 = 7.5). Also inhibits phosphorylated Erk (pIC50 = 7.1). Decreases cell number and viability in chronic lymphocytic leukemia (CCL) cell lines. Liddle et al (2011) Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor. Bioorg.Med.Chem.Lett. 21 6188 PMID:21903390 |Varghese et al (2018) Highly selective SYK inhibitor, GSK143, abrogates survival signals in chronic lymphocytic leukaemia. Br.J.Haematol 182 927 PMID:28770560

PDGFRα/FLT3-ITD-IN-3 (Compound 18d) is a potent inhibitor of PDGFRα (IC50: 0.153 μM), FLT3 (IC50: 0.004 μM) and PDGFRα/FLT3-ITD-IN-3 has the potential to be studied in acute myeloid leukaemia or chronic eosinophilic leukaemia. .

KDM4C-IN-1 is a selective and potent KDM4C inhibitor (IC50: 8 nM) with potential anticancer activity.KDM4C-IN-1 inhibits the growth of HepG2 and A549 cells, and can be used for the study of leukaemia.

Cytosine (6-Aminopyrimidin-2(1H)-one) is a pyrimidine base that is a fundamental unit of nucleic acids. The deamination of cytosine alone is apparent and the nucleotide of cytosine is the prime mutagenic nucleotide in leukaemia and cancer.

RG7775, also known as RO 6839921, a small molecule prodrug for the treatment of solid tumours and acute myeloid leukaemia.

FLT3/TrKA-IN-1 is a potent FLT3/TrKA dual kinase inhibitor, capable of acting on FLT3 (IC50: 43.8 nM), FLT3-ITD (IC50: 97.2 nM), FLT3-TKD (IC50: 92.5 nM) and TrKA (IC50: 23.6 nM). -FLT3/TrKA-IN-1 has potential for acute myeloid leukaemia (AML) studies.

FLT3/ITD-IN-4 (Compound 16) is a selective inhibitor of FLT3 internal tandem repeat mutations (FLT3-ITD) (IC50: 2.3 nM). FLT3/ITD-IN-4 can be used to study acute myeloid leukaemia.

TAS-103 is a dual inhibitor of DNA topoisomerase I/II, used for cancer research. TAS-103 is a dual inhibitor of DNA topoisomerase I/II. TAS-103 (0.1-10 μM) is active on CCRF-CEM cells, with an IC50 value of 5 nM. TAS-103 (0.1 μM) significantly increases levels of topo IIα FITC immunofluorescence in individual CCRF-CEM cells[1]. TAS-103 (0.01-1 μM) is highly cytotoxic to Lewis lung carcinoma (LLC) cells, and Liposomal TAS-103 is almost as active as free TAS-103[2]. TAS-103 inhibits the viability of HeLa cells, with an IC50 of 40 nM. TAS-103 (10 μM) disrupts signal recognition particle (SRP) complex formation, and induces destabilization of SRP14 and SRP19 and its eventual degradation[3]. TAS-103 (30 mg/kg, i.v.) causes significant tumor growth suppression in mice bearing Lewis lung carcinoma (LLC) cells, without obvious body weight loss, and the liposomal TAS-103 is more active than free TAS-103[2]. [1]. Padget K, et al. An investigation into the formation of N- [2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) and 6-[2-(dimethylamino)ethylamino]- 3-hydroxy-7H-indeno[2, 1-C]quinolin-7-one dihydrochloride (TAS-103) stabilised DNA topoisomerase I and II cleavable complexes in human leukaemia cells. Biochem Pharmacol. 2000 Sep 15;60(6):817-21. [2]. Shimizu K, et al. Cancer chemotherapy by liposomal 6-[12-(dimethylamino)ethyl]aminol-3-hydroxy-7H-indeno[2,1-clquinolin-7-one dihydrochloride (TAS-103), a novel anti-cancer agent. Biol Pharm Bull. 2002 Oct;25(10):1385-7. [3]. Yoshida M, et al. A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized affinity beads. Mol Pharmacol. 2008 Mar;73(3):987-94. Epub 2007 Dec 18.

DB818 is a synthetic Homeobox A9 (HOXA9) inhibitor and can be used for research on the treatment of acute myeloid leukaemia associated with HOXA9 overexpression.

MS177, a potent and rapid EZH2 degrader, functions as a PROTAC comprised of a CRBN ligand, linker, and a powerful enzymatic EZH2 inhibitor C24 (C24 IC50: 12 nM). It successfully targets and depletes both canonical EZH2–PRC2 and noncanonical EZH2–cMyc complexes. Furthermore, MS177 inhibits leukemia cell growth, induces apoptosis, and arrests cell cycle progression.

ODN 1585 is a potent inducer of IFN and TNFα production, a potent stimulator of NK (natural killer) and can be used as a vaccine adjuvant.ODN 1585 enhances the function of CD8+ T cells, including CD8+ T cell-mediated IFN-γ production.ODN 1585 induces regression of established melanomas in mice and has been shown to inhibit malaria in mice. ODN 1585 can be used to study acute myelogenous leukaemia (AML) and malaria.

The mixture of cabraleone and ocotillone shows cytotoxicity against HL-60 leukaemia cell line.

LSD1-IN-13 (compound 7e) is an orally active LSD1 inhibitor (IC50: 24.43 nM) that also activates CD86 expression (EC50: 470 nM).LSD1-IN-13 induces differentiation of AML (acute myeloid leukaemia) cell lines.

DHODH-IN-22 is a potent, selective, orally active inhibitor of dihydroorotic dehydrogenase (DHODH) (IC50: 0.3 nM) and can be used in acute myeloid leukaemia (AML) studies.

PI3K-IN-34 (Compound 6g) is a highly selective inhibitor of PI3K that acts on PI3K-α (IC50: 11.73 μM), PI3K-β (IC50: 6.09 μM) and PI3K-δ (IC50: 11.18 μM). PI3K-IN-34 can be used to study leukaemia.

AZD-1897 is an ATP-competitive pan-PIM inhibitor. When combined with the Akt inhibitor AZD5363, AML cells from putative leukaemia stem cells incur a reduction in levels of the anti-apoptotic protein MCL1. The combination of PIM and Akt inhibition holds promise for the treatment of AML.

Mitoxantrone dihydrochloride (NSC-301739) is the hydrochloride salt of an anthracenedione antibiotic with antineoplastic activity. It is a type II topoisomerase inhibitor.

MAX-40279 hydrochloride is a potent, dual inhibitor of FLT3 kinase and FGFR kinase. MAX-40279 hydrochloride has potential for acute myeloid leukaemia (AML) studies .