University of Puerto Rico

Bristol-myers Squibb Compnay

Cornelis P Vlaar

Suranganie Dharmawardhane Flanagan

Eliud Hernandez-O'Farrill

Linette Castillo-Pichardo

Jingyang Zhu

Eliud Hernandez

Suranganie Dharmawardhane

Edgar I Miranda

Eliud Hernandez-o'farrill

Eliud Hernandez-O'farrill

Compounds are disclosed that inhibit RhoGTPases that are useful for inhibiting hyperprofilerative and neoplastic diseases. Specifically, the compounds inhibit the GTPases Rac and Cdc42 that are overactive or overexpressed in signaling pathways in cancer and metastasis. Methods for treatment of cancer and hyperproliferative diseases are disclosed.

1,5-disubstituted 1,2,3-triazoles are inhibitors of Rac/CDC42 GTPases

A series of novel EHop-016 derivatives is presented herein via designing and synthesizing compounds that mimics its more favorable 'U-shaped' conformation that appears to be critical for inhibitory activity against Rac. Based on modeling studies on EHop-016, compounds with a more rigid structural conformation can mimic this 'U-shaped' conformation and would improve the anti-migration activity against metastatic cells. Compounds are disclosed that inhibit RhoGTPases that are useful for inhibiting hyperprofilerative and neoplastic diseases, for instance compounds of formula  Specifically, the compounds inhibit the GTPases Rac and Cdc42 that are overactive or overexpressed in signaling pathways in cancer and metastasis. Methods for treatment of cancer and hyperproliferative diseases are disclosed.

Carbazole EHop-016 derivatives as anticancer and anti-migratory agents

Compounds are disclosed that inhibit RhoGTPases that are useful for inhibiting hyperproliferative and neoplastic diseases. Specifically, the compounds inhibit the GTPases Rac and Cdc42 that are overactive or overexpressed in signaling pathways in cancer and metastasis. Methods for treatment of cancer and hyperproliferative diseases are disclosed.

1,5-disubstituted 1,2,3-triazoles are inhibitors of Rac/Cdc42 GTPases

1,5-disubstituted 1,2,3-triazoles are inhibitors of RAC/CDC42 GTPases

A series of novel EHop-016 derivatives is presented herein via designing and synthesizing compounds that mimics its more favorable 'U-shaped' conformation that appears to be critical for inhibitory activity against Rac. Based on modeling studies on EHop-016, compounds with a more rigid structural conformation can mimic this 'U-shaped' conformation would improve the anti-migration activity against metastatic cells. Compounds are disclosed that inhibit RhoGTPases that are useful for inhibiting hyperprofilerative and neoplastic diseases, for instance compounds of formula (I)  Specifically, the compounds inhibit the GTPases Rac and Cdc42 that are overactive or overexpressed in signaling pathways in cancer and metastasis. Methods for treatment of cancer and hyperproliferative diseases are disclosed.

Carbazole EHop-016 derivatives as anti-cancer and anti-migratory agents

1,5-Disubstituted 1,2,3-triazoles are inhibitors of Rac/Cdc42 GTPases

A novel inhibitor of Rac activity based on the structure of the established Rac/Rac-GEF inhibitor NSC23766 is discloses. The compound EHop-016, with an IC50 of 1.1 &#x3bc;M, is a 100-fold more efficient inhibitor of Rac activity than NSC23766. EHop-016 is specific for Rac1 and Rac3 at concentrations &#x2266;5 mM. At higher concentrations, EHop-016 inhibits the close homolog Cdc42. In MDA-MB-435 cells, EHop-016 (&#x2266;5 mM) inhibits the association of the Rac-GEF Vav2 with a nucleotide-free Rac1(G15A), which has a high affinity for activated GEFs. EHop-016 does not affect the association of the Rac-GEF Tiam-1 with Rac1(G15A) at similar concentrations. EHop-016 also inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation in both cell lines. EHop-016 decreases Rac-downstream effects of p21-activated kinase (PAK)1 activity and directed migration of metastatic cancer cells. At low concentrations (&#x3c;5 &#x3bc;M), EHop-016 does not affect cell viability.

Small-molecule inhibitors of Rac1 in metastatic cancer cells

Small-molecule inhibitors of Rac1 in metastatic breast cancer

A method for preparing irbesartan and intermediates thereof. Irbesartan has the structure of formula I, 

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San Juan, Puerto Rico

Cornelis P Vlaar