lymphocytic

Cladribine (2CdA), an adenosine deaminase inhibitor, is utilized in the treatment of lymphoproliferative diseases.

Acalabrutinib (ACP-196), also known as ACP-196, is an orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, ACP-196 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

Ibrutinib (PCI-32765) is an irreversible inhibitor of BTK (IC50: 0.5 nM) that selectively blocks B cell activation.

GS-9901 is a selective, orally active and potent PI3Kδ inhibitor (IC50: 1 nM) for the study of non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

Bcl-xL antagonist 2 is an effective and selective antagonist of Bcl-xL with an IC50 of 91 nM and a Ki of 65 nM. Bcl-xL antagonist 2 induces apoptosis in cancer cells and can be used in studies about chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

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.

MP07-66 is a novel FTY720-analog devoid of immunosuppressive effects leads to the reactivation of PP2A, which in turn triggers apoptosis of CLL cells.

Lisaftoclax (Bcl-2 Bcl-xl inhibitor 1) is an oral dual inhibitor of Bcl-2 and Bcl-xl, with IC50 values of 2 nM and 5.9 nM for Bcl-2 and Bcl-xl, respectively. Lisaftoclax is used to treat chronic lymphocytic leukemia (CLL) by inhibiting the action of the BCL-2 protein, which promotes the death of leukemia cells.

Orelabrutinib (ICP-022) is an orally active and irreversible inhibitor of Bruton's tyrosine kinase (BTK).

MT-802 is an effective BTK degrader based on PROTAC technology (DC50: 1 nM). MT-802 has the potential to treat C481S mutant chronic lymphocytic leukemia (CLL).

8-Chloroadenosine (NSC-354258) is a 5' AMP-activated protein kinase agonist potentially for the treatment of chronic lymphocytic leukemia. 8-chloroadenosine activity is associated with inhibition of the mTOR pathway.8-Chloroadenosine (NSC-354258) is a nucleoside analog; metabolized in vivo to 8-Chloro-ATP. Incorporates into RNA during transcription and inhibits RNA synthesis. Exhibits cytotoxicity in MM.1S, RPMI-8226, and U266 cancer cell lines; induces G2 M cell cycle arrest and mitotic catastrophe in A549 and H1299 cells. 8-Chloroadenosine (NSC-354258) has been shown to deplete ATP and inhibit tumor growth in hematological malignancies as well as in lung and breast cancer cell lines.

PROTAC BTK Degrader-10 (Example 1P) is a PROTAC compound that targets BTK for degradation. It is applicable in the research of chronic lymphocytic leukemia (CLL). [Pink: ligand for target protein; Black: linker; Blue: ligand for E3 ligase Cereblon].

Lonitoclax is an inhibitor of B-cell lymphoma 2 (Bcl-2). It demonstrates antitumor activity in B-cell and myeloid malignancy models comparable to Venetoclax. Lonitoclax holds potential for research in relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, and certain low-grade lymphomas.

TAN 420E is a bacterial metabolite originally isolated from Streptomyces. It scavenges 2,2-diphenyl-1-picrylhydrazyl radicals in a cell-free assay (IC50 = 1.3 μM) and reduces thiobarbituric acid reactive substances (TBARS) in rat liver microsomes by 72% when used at a concentration of 100 μg/ml. TAN 420E is active against B. brevis, B. cereus, M. flavus, and S. aureus (MICs = 50-100 μg/ml). It is cytotoxic to P388 and KB lymphocytic leukemia cells (EC50s = 0.022 and 0.3 μg/ml, respectively).

High affinity XIAP antagonist (Kd = 16 nM for the BIR3 domain of XIAP). Exhibits cytotoxicity in a wide range of cancer cell lines in vitro (EC50 = 13 nM in MDA-MB-231 cells). Also displays antitumor activity in a mouse breast cancer xenograft model. Enhances TRAIL-induced apoptosis in chronic lymphocytic leukemia (CLL) cells. Oost et al (2004) Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer. J.Med.Chem. 47 4417 PMID:15317454 |Loeder et al (2009) A novel paradigm to trigger apoptosis in chronic lymphocytic leukemia. Cancer Res. 69 8977 PMID:19920200

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

Altemicidin is a monoterpene alkaloid originally isolated from [S. sioyaensis] with acaricidal and anticancer activities. It is effective against two-spotted spider mites ([T. urticae]) in a greenhouse pot test at concentrations of 10 and 100 ppm. Altemicidin inhibits the growth of murine L1210 lymphocytic leukemia and IMC carcinoma cells (IC50s = 0.84 and 0.82 μg ml, respectively). It is toxic to mice with an LD50 value of 0.3 mg kg.

LCMV GP (61-80) is a 61-80 amino acid sequence peptide fragment derived from the lymphocytic choroid plexus meningitis virus (LCMV) glycoprotein (GP), which is a specific antigenic determinant that induces CD4+ T cell responses.

Umbralisib (TGR 1202) is a PI3Kδ inhibitor.

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.

Oxanosine is an analog of guanosine that has been found in S. capreolus and has diverse biological activities, including antibacterial, antiviral, and anticancer properties. It is active against a variety of bacteria, including S. flexneri, P. mirabilis, and E. coli (MICs = 6.25, 12.5, 25 µg ml, respectively, on peptone, but not nutrient, agar). Oxanosine inhibits replication of the HIV-1 strain IIIb in infected CEM and U937, but not H9, cells (EC50s = 7, 27, and >500 µg ml, respectively). It also inhibits the growth of HeLa human cervical cancer cells (IC50 = 32 µg ml) and reduces tumor growth in a murine L1210 lymphocytic leukemia model.

Amoorastatin is a natural product that has been studied in cancer research. Its derivative was found to significantly inhibit growth of the murine P388 lymphocytic leukemia cell lines.

Olcorolimus inhibits single allergen-induced allergic inflammation such as eosinophilic and lymphocytic infiltration and mRNA expression for interleukin (IL)-4 and IL-5

CI-898 HCl is a lipophilic antifolate inhibitor of dihydrofolate reductase (DHFR). It has enhanced binding to DHFR in the presence of the cofactor NADPH. Cl-898 HCl inhibits cell growth and halts the cell cycle at the G1 S phase in L1210 mouse lymphocytic leukemia cells and is active against methotrexate-resistant cancer cell lines. It also enhances the activity of doxorubicin, cyclophosphamide, and 6-thioguanine (6-TG) in mice with advanced stage P338 leukemia.