Methods to Impair Hematologic Cancer Progenitor Cells and Compounds Related Thereto

Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leuke mia (CML) and chronic lymphoid leukemia (CLL). Interleu kin-3 receptor alpha chain (IL-3Ra or CD123) is strongly expressed on progenitor hematologic cancer cells, but is vir tually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hemato logic cancer (e.g., leukemia and lymphomic) cells by selec tively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malig nant lymphoproliferative disorders. Also provided are com pounds useful for selectively binding to CD123 and impairing progenitor hematologic cancer cells. These compounds may include cytotoxic moieties such as, for example, radioiso topes or chemotherapeutics

Use of Parthenolide Derivatives as Antileukemic and Cytotoxic Agents

To read this abstract, please download this patent

Use of Parthenolide Derivatives as Antileukemic and Cytotoxic Agents

To read this abstract, please download this patent

Use of Parthenolide Derivatives as Antileukemic and Cytotoxic Agents

Compounds of the formula having anti-tumor activity, wherein R1 and R2 are as described herei

Use of Parthenolide Derivatives as Antileukemic and Cytotoxic Agents

To view this abstract, please download this patent

Use of Parthenolide Derivatives as Antileukemic and Cytotoxic Agents

To view this abstract, please download this patent

Melampomagnolide B Derivatives as Antileukemic and Cytotoxic Agents

Melampomagnolide B is disclosed as a new antileukemic sesquiterpene. A biotin-conjugated derivative of melampomagnolide B was prepared to elucidate its mechanism of action. Prodrugs of Melampomagnolide B are disclosed

Caracterización fisicoquímica de películas formuladas a partir de proteína y mucílago de chía (Salvia hispanica, L.)

Una alternativa para el uso de plásticos que contribuyen al incremento de la contaminación ambiental, son los polímeros biodegradables producidos a partir de fuentes naturales como las semillas de chía. A partir de ella se pueden extraer componentes como la proteína y mucílago para la elaboración de películas. Las características fisicoquímicas de las películas influyen en gran medida en sus propiedades, es por ello que su conocimiento es relevante pues determinará sus potenciales aplicaciones

MMB triazole analogs are potent NF-κB inhibitors and anti-cancer agents against both hematological and solid tumor cells

Triazole derivatives of melampomagnolide B (MMB) have been synthesized via click chemistry methodologies and screened against a panel of 60 human cancer cell lines. Several derivatives showed promising anti-cancer activity, affording growth inhibition (GI50) values in the nanomolar range (GI50 = 0.02–0.99 μM). Lead compound 7h exhibited EC50 values of 400 nM and 700 nM, respectively, against two AML clinical specimens. Compound 7h was significantly more potent than parthenolide as an inhibitor of p65 phosphorylation in both hematological and solid tumor cell lines, indicating its ability to inhibit the NF-κB pathway. In TMD-231 breast cancer cells, treatment with 7h reduced DNA binding activity of NF-κB through inhibition of IKK-β mediated p65 phosphorylation and caused elevation of basal IκBα levels through inhibition of constitutive IκBα turnover and NF-κB activation. Molecular docking and dynamic modeling studies indicated that 7h interacts with the kinase domain of the monomeric IKKβ subunit, leading to inhibition of IKKβ activation, and compromising phosphorylation of downstream targets of the NF-κB pathway; dynamic modeling studies show that this interaction also causes unwinding of the α-helix of the NEMO binding site on IKKβ. Molecular docking studies with 10, a water-soluble analog of 7h, demonstrate that this analog interacts with the dimerization/oligomerization domain of monomeric IKKβ and may inhibit oligomer formation and subsequent autophosphorylation. Sesquiterpene lactones 7h and 10 are considered ideal candidates for potential clinical development