c ABL IN 1

C-ABL-IN-1 is a new and specific inhibitor of the c-Abl protein, which effectively prevents the progression of neurodegeneration observed in Parkinson's disease.

OSI-930, an orally active inhibitor of c-Kit and the vascular endothelial growth factor receptor-2 (VEGFR-2), targets cancer cell proliferation and blood vessel growth (angiogenesis) in tumors.

cSRC BCR-ABL-IN-1 (compound 21b) is a potent inhibitor of Bcr-Abl and C-Src, with IC50 values of 56.2 nM and 101 nM, respectively. It exhibits cytotoxicity.

C-ABL-IN-2 is a highly effective inhibitor of the c-Abl protein, which plays a significant role in the development of several diseases, including cancer. This compound exhibits promise for investigating neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), as well as cancer. (Source: WO2020260871A1, compound 25) [1].

c-ABL-IN-3, a highly effective c-Abl inhibitor, exhibits promising potential for studying neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), as well as cancer [1]. The activation of c-Abl has been strongly implicated in a range of diseases, notably cancer [1]. It offers valuable opportunities for research in these fields [1].

Imatinib Impurity E is a specific impurity found in Imatinib, an orally available inhibitor of multiple tyrosine kinases, including BCR ABL, v-Abl, PDGFR, and c-kit. Imatinib (STI571) operates by semi-competitively inhibiting enzyme activity; it binds adjacent to the ATP binding site, inducing a closed or self-inhibited conformation [1] [2] [3] [4]. Additionally, Imatinib acts as an inhibitor against SARS-CoV and MERS-CoV [5].

C-ABL-IN-5, a selective c-Abl inhibitor, exhibits neuroprotective properties and has favorable characteristics including blood-brain barrier permeability, metabolic stability, and pharmacokinetic profiles. When labeled with [18F] (compound [18F]3), C-ABL-IN-5 serves as a tracer in positron emission tomography (PET) scans to assess disease-modifying effects, particularly in research on neurodegenerative conditions like Parkinson's disease (PD) [1].

Protein kinase D (PKD), a serine threonine protein kinase activated by diacylglycerol downstream of PKC signaling, has three human isoforms that modulate cell proliferation, survival, invasion, and protein transport. CRT0066101 acts as an inhibitor of these three PKD isoforms, with IC50 values of 1, 2.5, and 2 nM for PKD1, PKD2, and PKD3, respectively. It demonstrates selectivity for PKD over a range of more than 90 protein kinases, including PKCα, PKBα, MEK, ERK, c-Raf, c-Src, and c-Abl. This specificity allows CRT0066101 to inhibit cell proliferation, induce apoptosis, and notably reduce the viability of pancreatic cancer cells both in vitro and in vivo.

GNF-6 (Compound 14), an ATP competitive inhibitor, inhibits the gatekeeper threonine residue mutation of BCR-ABL-T315I with IC50 values of 0.25 μM for c-ABL-T334I, 0.09 μM for BCR-ABL, and 0.590 μM for BCR-ABL-T315I variants. It disrupts the assembly of the hydrophobic spine (a network of hydrophobic interactions), locking the kinase in an inactive 'DFG-out' conformation [1].