CLL

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

TAT-cyclo-CLLFVY TFA is a cyclic peptide inhibitor targeting HIF-1 heterodimerization to mitigate hypoxia signaling within cancer cells. It effectively disrupts the protein-protein interaction between HIF-1α and HIF-1β, with an inhibitory concentration (IC 50) of 1.3 μM [1].

Selective HIF-1 dimerization inhibitor. Blocks protein-protein interaction of recombinant HIF-1α, but not HIF-2α, with HIF-1β (IC50 = 1.3 μM). Inhibits hypoxia-induced HIF-1 activity, and decreases VEGF and CAIX expression in osteosarcoma and breast cance

Cyclo(CLLFVY) is an inhibitor of hypoxia-inducible factor-1 (HIF-1), exhibiting half-maximal inhibitory concentrations (IC50) of 19 μM in U2OS cells and 16 μM in MCF-7 cells. It binds to the PAS-B domain of HIF-1α, inhibiting the dimerization and transcriptional activity of HIF-1. Moreover, cyclo(CLLFVY) downregulates the expression of hypoxia response genes (such as VEGF and CAIX), demonstrating antitumor effects against HIF-1-related cancers.

B I09, an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells., an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells., an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells.

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

Isoprenaline hydrochloride (NCI-c55630) is a potent beta-adrenergic agonist with the peripheral vasodilator, bronchodilator, and cardiac stimulating properties.

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.

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.

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.

CDKI-73 is a potent CDK9 inhibitor (Ki: 4 nM). It shows selective toxicity to CLL cells(LD50=80 nM) versus normal B cell and normal CD34+ cell(LD50>20 uM).The inhibition of CDK9 induces apoptosis and potentiates the effect of cisplatin.

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).

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.

Adaphostin (NSC-680410) is a p210Bcr Abl tyrosine kinase inhibitor with IC50 of 14 μM.

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

TAK-659 hydrochloride (TAK-659) is a potent and selective inhibitor of spleen tyrosine kinase (SYK) with an IC50 value of 3.2 nM. It is selective against most other kinases, but potent toward both SYK and FLT3.

Umbralisib (TGR 1202) is a PI3Kδ inhibitor.

Mitoxantrone diacetate is a potent inhibitor of topoisomerase II. Mitoxantrone diacetate also inhibits protein kinase C (PKC) (IC50: 8.5 μM). Mitoxantrone diacetate exhibits antitumour effects and also has an antiorthopoxvirus effect, acting against bovine pox (EC50: 0.25 μM) and monkey pox (EC50: 0.8 μM).

Umbralisib Tosylate (TGR-1202) is a potent, selectively dual inhibitor targeting PI3Kδ and casein kinase-1-ε (CK1ε), demonstrating oral activity. With EC50 values of 22.2 nM and 6.0 μM for PI3Kδ and CK1ε respectively, it shows unique immunomodulatory effects on T cells in chronic lymphocytic leukemia (CLL). This compound is utilized in the research of hematological malignancies.

Umbralisib (TGR-1202) sulfate, an orally active compound, serves as a potent, selective inhibitor targeting both PI3Kδ and casein kinase-1-ε (CK1ε), with EC50 values of 22.2 nM and 6.0 μM, respectively. It demonstrates unique immunomodulatory effects on T cells in chronic lymphocytic leukemia (CLL) and is applicable in the research of hematological malignancies.

Lucatumumab (HCD122) is a fully human anti-CD40 monoclonal antibody with antitumor activity that blocks the interaction of CD40L with CD40 and inhibits the CD40 CD40L-mediated signaling pathway for the study of chronic lymphocytic leukemia (CLL) and multiple myeloma.

Ulocuplumab (BMS-936564) is a fully human anti-CXCR4 IgG4 antibody.Ulocplumab exhibits antitumor activity in acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL), and multiple myeloma transplantation models.Ulocplumab inhibits the migration of chronic lymphocytic leukemia (CLL) cells under CXCR4 activation, induces apoptosis, and inhibits the growth and migration of cancer cells. Ulocplumab inhibits CXCL12-mediated chronic lymphocytic leukemia (CLL) cell migration in response to CXCR4 activation and induces apoptosis.)