lymphoblastic

Revumenib (SNDX-5613) is a potent and selective oral inhibitor of menin-KMT2A interaction with Ki of 0.149 nM and IC50 between 10 and 20 nM, which can be used in the study of acute leukemia with MLL gene rearrangement.

Methotrexate (WR19039) is a folate analog, an inhibitor of the dihydrofolate reductase DHFR. Methotrexate has antimetabolic, antitumor, and immunosuppressive activities, and is commonly used in rheumatoid arthritis and various tumors.

Pivanex (Pivalyloxymethyl butyrate) is an orally active HDAC inhibitor and an antimetastatic and antiangiogenic agent. Pivanex downregulates the Bcr-Abl protein and enhances apoptosis.

(Rac)-SHIN2, a serine hydroxymethyltransferase (SHMT) inhibitor, enhances NOTCH1-driven in vivo survival of primary T-ALL in mice and is useful for studying T-cell acute lymphoblastic leukemia (T-ALL).

Pheniramine maleate (Trimetose), an alkylamine derivative with antihistaminic and vasodilatory properties, binds to histamine H1 receptors, thereby inhibiting phospholipase A2 and production of the endothelium-derived relaxing factor, nitric oxide.

Methotrexate disodium is an tetrahydrofolate dehydrogenase inhibitor

UNC 569 hydrochloride is a reversible and ATP-competitive inhibitor of Mer with an IC50 of 2.9 nM and a Ki of 4.3 nM. UNC 569 hydrochloride inhibits Axl and Tyro3 with IC50s of 37 nM and 48 nM, respectively. UNC 569 hydrochloride can be used in studies about acute lymphoblastic leukemia and atypical teratoid rhabdoid tumors.

Daunorubicin is an anthracycline antibiotic and topoisomerase II inhibitor with anticancer activity, inhibiting DNA and RNA synthesis, and is commonly used to treat acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL).

CAD204520 functions as an inhibitor of SERCA (IC50 = 0.34 μM), specifically targeting mutations in the wild-type NOTCH1 protein associated with T-cell acute lymphoblastic leukemia (T-ALL) and mantle cell lymphoma (MCL).

Revumenib (also known as SNDX-5613) is an effective and selective Menin-MLL inhibitor. It is primarily used for the study of MLL-rearranged (MLL-r) acute leukemias, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

AcBut-N-Ac-γ-Calicheamicin serves as a toxic molecule for ADCs, inducing cell cycle arrest and apoptosis (Apoptosis) by causing DNA double-strand breaks. Primarily utilized in the synthesis of antibody-drug conjugates (ADC), it holds promise for cancer research, particularly in studies related to acute lymphoblastic leukemia (ALL) and other hematological malignancies.

PKN3-IN-1 (compound 16) inhibits PKN3 (serine threonine-protein kinase N3) and GAK (cyclin G-associated kinase) with an IC50 of 0.014 μM and a Ki of 0.0044 μM. PKN3-IN-1 is a potential tool compound for investigating the cell biology of PKN3 and its role in pancreatic and prostate cancers, as well as T-cell acute lymphoblastic leukemia.

Proteasome-IN-7 (Compound 6f) is a macrolactam-based epoxyketone proteasome inhibitor with an IC50 value of 37.92 nM against the 20S proteasome ChT-L subunit. It exhibits potent antiproliferative effects on multiple myeloma, acute lymphoblastic leukemia, and non-small cell lung cancer.

Metanilic acid, an anti-cancer drug, is used to treat several malignancies including choriocarcinoma and pediatric acute lymphoblastic leukemia.

J9 is an inhibitor of Glucocorticoid resistance. J9 reverses Dexamethasone Resistance in T-cell Acute Lymphoblastic Leukemia.

Acetylaleuritolic acid is a pentacyclic triterpenoid, plant metabolite isolated from the leaves of Garcinia miniata. It has antitumor properties, showing tumor inhibitory activity in tests against P-388 lymphoblastic leukemia.

Calaspargase pegol is used to treat acute lymphoblastic leukemia.

Erythrofuranosyladenine(9-beta-D-Erythrofuranosyladenine, ETA) is a nontoxic MTAP substrate. Erythrofuranosyladenine is an effective salvage agent for methylthioadenosine phosphorylase–selective therapy of T-cell acute lymphoblastic leukemia with L-alanos

C24 dihydro Ceramide is a sphingolipid that has been found in the stratum corneum of human skin.[1] It is found in higher concentrations in female sebum compared to male sebum.[2] C24 dihydro Ceramide levels positively correlate with cytotoxicity in CCRF-CEM, MOLT-4, COG-LL-317h, and COG-LL-332h T cell acute lymphoblastic leukemia (ALL) cell lines.[4] Levels of C24 dihydro ceramide are increased by 149.49-fold in dihydroceramide desaturase 1 (DEGS1) knockdown UM-SCC-22A human head and neck squamous carcinoma cells in vitro.[4] C24 dihydro Ceramide levels are also increased in INS-1 β-cells incubated with glucose and palmitate.[5]

HDAC3 inhibitor is an allosteric inhibitor of histone deacetylase 3 (HDAC3; Ki = 0.16 nM). It is selective for HDAC3 over HDAC1 and HDAC2 (IC50s = 0.95, 11.81, and 95.45 nM, respectively, using recombinant HDACs). In addition, it is selective for acute myeloid, monocytic, and lymphoblastic leukemia cell lines (EC50s = 36.37, 76.64, and 151.7 nM, respectively) over chronic myeloid, acute promyelocytic, and acute lymphoblastic cells (EC50s = 2,160, >10,000, and >10,000 nM, respectively).

Ara-G is an analog of the nucleoside guanosine and an active metabolite of nelarabine .1,2 Ara-G accumulates in T lymphoblasts and malignant T-lymphoid cells, where it is phosphorylated to produce ara-GTP and incorporated into the DNA.3,1 Ara-G inhibits DNA replication by 92% after 30 minutes when used at a concentration of 50 μM in CEM cells, which are used as a model for human T lymphoblasts.1 It also halts the cell cycle at the sub-G1 phase and induces apoptosis in CEM cells.3 Syngeneic bone marrow containing 6C3HED tumor cells treated with ara-G (100 mM) ex vivo prior to transplantation increases survival of lethally irradiated mice and induces reconstitution of lymphoid, myeloid, and erythroid cell linages.4References1. Leanza, L., Miazzi, C., Ferraro, P., et al. Activation of guanine-β-D-arabinofuranoside and deoxyguanosine to triphosphates by a common pathway blocks T lymphoblasts at different checkpoints. Exp. Cell Res. 316(20), 3443-3453 (2010).2. Lambe, C.U., Averett, D.R., Paff, M.T., et al. 2-Amino-6-methoxypurine arabinoside: An agent for T-cell malignancies. Cancer Res. 55(15), 3352-3356 (1995).3. Rodriguez, C.O., Jr., Stellrecht, C.M., and Gandhi, V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood 102(5), 1842-1848 (2003).4. Kurtzberg, J. Guanine arabinoside as a bone marrow-purging agent. Ann. N.Y. Acad. Sci 685(1), 225-236 (1993). Ara-G is an analog of the nucleoside guanosine and an active metabolite of nelarabine .1,2 Ara-G accumulates in T lymphoblasts and malignant T-lymphoid cells, where it is phosphorylated to produce ara-GTP and incorporated into the DNA.3,1 Ara-G inhibits DNA replication by 92% after 30 minutes when used at a concentration of 50 μM in CEM cells, which are used as a model for human T lymphoblasts.1 It also halts the cell cycle at the sub-G1 phase and induces apoptosis in CEM cells.3 Syngeneic bone marrow containing 6C3HED tumor cells treated with ara-G (100 mM) ex vivo prior to transplantation increases survival of lethally irradiated mice and induces reconstitution of lymphoid, myeloid, and erythroid cell linages.4 References1. Leanza, L., Miazzi, C., Ferraro, P., et al. Activation of guanine-β-D-arabinofuranoside and deoxyguanosine to triphosphates by a common pathway blocks T lymphoblasts at different checkpoints. Exp. Cell Res. 316(20), 3443-3453 (2010).2. Lambe, C.U., Averett, D.R., Paff, M.T., et al. 2-Amino-6-methoxypurine arabinoside: An agent for T-cell malignancies. Cancer Res. 55(15), 3352-3356 (1995).3. Rodriguez, C.O., Jr., Stellrecht, C.M., and Gandhi, V. Mechanisms for T-cell selective cytotoxicity of arabinosylguanine. Blood 102(5), 1842-1848 (2003).4. Kurtzberg, J. Guanine arabinoside as a bone marrow-purging agent. Ann. N.Y. Acad. Sci 685(1), 225-236 (1993).

NR-160 is an inhibitor of histone deacetylase 6 (HDAC6; IC50= 0.03 μM).1It is selective for HDAC6 over HDAC1, -2, -3, -4, and -8 (IC50s = 5.18, 2.26, 8.48, 55.4, and 14.7 μM, respectively). NR-160 is cytotoxic against a panel of seven cancer cell lines (IC50s = 22.5-51.8 μM). It enhances cytotoxicity induced by bortezomib in HL-60 cells, as well as cytotoxicity induced by epirubicin or daunorubicin in CCRF-HSB-2 T cell acute lymphoblastic leukemia cells.

S2157, a potent N-alkylated tranylcypromine (TCP) derivative lysine-specific demethylase 1 (LSD1) inhibitor, enhances H3K9 methylation and concurrently reduces H3K27 acetylation at super-enhancer sites. This compound triggers apoptosis in TCP-resistant T-cell acute lymphoblastic leukemia (T-ALL) cells by inhibiting NOTCH3 and TAL1 gene expression. Moreover, S2157 is capable of crossing the blood-brain barrier, effectively eliminating central nervous system (CNS) leukemia in mice models implanted with T-ALL cells.

S2116 is a powerful inhibitor of lysine-specific demethylase 1 (LSD1), and it is a derivative of N-alkylated tranylcypromine (TCP). S2116 exhibits its inhibitory effects by increasing H3K9 methylation and inducing reciprocal H3K27 deacetylation at super-enhancer regions. In TCP-resistant T-cell acute lymphoblastic leukemia (T-ALL) cells, S2116 triggers apoptosis by repressing the transcription of NOTCH3 and TAL1 genes. Furthermore, S2116 demonstrates significant growth retardation of T-ALL cells when xenotransplanted into mice.