lymphocytic leukemia

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

Umbralisib (TGR 1202) is a PI3Kδ inhibitor.

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.

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.

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.

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.

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.

TLT8 is a ByeTAC protein degrader that targets BTK. It induces BTK degradation by non-covalently binding to Rpn-13 and BTK. TLT8 is applicable in research on chronic lymphocytic leukemia.

DDD2 is a selective and efficient VHL-mediated PROTAC degrader specifically targeting NUDT5. It effectively induces substantial degradation of NUDT5. DDD2 consists of the warhead TH10184 and the VHL-recruiting ligand VH032, connected via a saturated aliphatic eight-carbon linker. DDD2 is applicable in cancer research, including studies on lymphocytic leukemia and osteosarcoma.

CFON-026 is a selective, orally active, non-covalent BTK inhibitor with an IC50 of 0.27 nM. It demonstrates significant antitumor activity against wild-type BTK (TMD8 and REC-1) as well as all clinically relevant BTK resistance mutations (BTKC481S, T474I, L528W, and V416L). CFON-026 induces complete tumor regression in the TMD8 xenograft mouse model. This compound is applicable for research into hematologic cancers, such as chronic lymphocytic leukemia and Waldenström's macroglobulinemia.

JP-163-16 is a RelA/p65 PROTAC degrader. It selectively reduces the expression of RelA/p65 in cells via a proteasome-dependent mechanism. JP-163-16 induces apoptosis by inhibiting the NF-κB signaling pathway. This compound is applicable for research on RelA/p65-dependent tumors, such as chronic lymphocytic leukemia (CLL).

FCN-338 (LOXO-338) is an orally active and selective Bcl-2 inhibitor, exhibiting an IC50 of 4.5 nM for the Bcl-2/BAK interaction. It effectively suppresses tumor growth in mouse models of follicular lymphoma (FL), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) xenografts without causing significant weight loss. FCN-338 demonstrates broad-spectrum anticancer activity, making it suitable for treating FL, chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL), AML, and ALL.

FGFR-IN-22 (Compound 23) is an FGFR inhibitor with IC50 values of 0.631 nM for FGFR1, 1.26 nM for FGFR2, 0.851 nM for FGFR3, and 1 nM for FGFR4. It effectively inhibits cell proliferation dependent on FGFR1 and FGFR3 signaling pathways. FGFR-IN-22 is applicable in research related to cancers such as chronic lymphocytic leukemia (CLL).

LFM-A13 is a highly selective inhibitor of the non-receptor tyrosine kinase BTK (Bruton's tyrosine kinase) (IC50 = 2.5 μM). It irreversibly severs the downstream signaling network of the B-cell receptor (BCR) by targeted binding to the BTK kinase catalytic domain, exhibiting excellent anti-leukemic and immunomodulatory effects in models of acute/chronic lymphocytic leukemia and severe autoimmune diseases.

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).

A410099.1 is a BIRC (baculoviral IAP repeat-containing protein) inhibitor with EC50 values of 4.6, 9.2, 15.6, 19.9, and 93.9 nM for BIRC2/3/4/7/8 respectively, suitable for studying E3 ligases and PROTAC synthesis.

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.