Delving into the Latest Updates on CA IX/XII and VEGFR-2 inhibitors(Kafrelsheikh University) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

SLC-0111 Analogues

Target

CA12 x CAIX x VEGFR2

Action

inhibitors, antagonists

Mechanism

CA12 inhibitors(carbonic anhydrase 12 inhibitors), CAIX inhibitors(Carbonic anhydrase IX inhibitors), VEGFR2 antagonists(Vascular endothelial growth factor receptor 2 antagonists)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Breast Cancer

Inactive Indication-

Originator Organization

Kafrelsheikh University

Active Organization

Kafrelsheikh University

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Presently, dual targeting by a single small molecule stands out as an effective cancer-fighting weapon. Carbonic anhydrase (CA) and vascular-endothelial growth factor (VEGF) are hypoxia-activatable genes that are implicated in tumorigenesis and progression of hypoxic tumors at different levels. Herein, we designed and synthesized 30 1,5-diaryl-1,2,4-triazole-tethered sulfonamides (11a-f, 12a-l, 13a-f, 15a-f) as novel SLC-0111 analogues with dual CA IX/XII and VEGFR-2 inhibitory activities. The 4-fluorophenyl SLC-0111 tail was replaced by substituted 1,5-diaryl-1,2,4-triazoles. Changing the sulfamoyl motif position provided regioisomers 11a-f and 12a-l. Elongation of the ureido linker yielded derivatives 15a-f. Inhibitory evaluations included a panel of hCAs (hCA I, II, IX, and XII) and screening against 60 cancer cell lines. Promising candidates were assessed for VEGFR-2 inhibition and selectivity and further evaluated on breast cancer cell lines (MCF-7 and T-47D) and the non-tumorigenic (MCF-10A) cells. Molecular docking studies explored the binding modes of the sulfonamides against hCA IX/XII and VEGFR-2 kinase.

100 Deals associated with CA IX/XII and VEGFR-2 inhibitors(Kafrelsheikh University)

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