Organometallic Ligands

<p>A brain-penetrant inhibitor of leucin-rich repeat kinase 2 (LRRK2) with IC50 = 0.76 nM and anti-parkinsonian activity. Gain-of-function mutations in LRRK2 gene lead to increased familial and idiopathic risk of developing the disease. The inhibitors of the kinase activity have therapeutic potential against Parkinson’s disease.</p>

<p>H+/K+ ATPase inhibitor</p>

<p>AR-R 17779 is a selective agonist for α7 nicotinic acetylcholine receptors (nAChRs) (Ki value = 190 nM for rat α7 receptor). This compound has use as a tool to study the function of α7 nicotinic receptors. One such study revealed a role for α7 nicotinic receptors in nicotine-mediated excitatory effects on hippocampal learning and memory. AR-R17779 reduces formation of atherosclerotic plaques and abdominal aortic aneurysms in apolipoprotein E-deficient mice.</p>

<p>Diclofenac is a non-steroidal anti-inflammatory drug that is used to treat the signs and symptoms of arthritis and osteoarthritis. This drug inhibits COX-1 and COX-2 enzymes. As a result, it reduces pain and inflammation in joints. Diclofenac is usually used as a first line therapy for acute and chronic pain.</p>

<p>DNA alkylating agent; highly potent metabolite of nemorubicin</p>

<p>A chemical probe for the dual bromodomains of human transcription-initiation-factor TFIID subunit 1 (TAF1). GNE 371 binds TAF1 with an IC50 of 10 nM and is selective over other bromodomain family members. Exerts anti-proliferative effects in synergy with BET inhibitor JQ1.</p>

<p>Phosphodiesterase inhibitor</p>

<p>PYR-41 is a small molecule inhibitor, which is sourced from chemical synthesis. It functions primarily by targeting ubiquitin-activating enzymes, particularly the E1 enzyme, to disrupt the ubiquitination process. This mechanism effectively hampers the transfer of ubiquitin to substrate proteins, thereby modulating protein degradation and signaling pathways.</p>

<p>CXCR2 antagonist</p>

<p>alpha-adrenoceptor agonist; nasal decongestant</p>

<p>BX471 hydrochloride is a selective antagonist of the C-C chemokine receptor type 1 (CCR1), which is synthesized through rigorous chemical processes. It operates by inhibiting the binding of chemokines to the CCR1 receptor, thus interfering with the signaling pathways that lead to inflammation and immune responses. This mechanism is specifically effective in modulating immune system functions and controlling pathophysiological responses in various tissue types.</p>

<p>Proteosome inhibitor; pro-apoptotic; has anti-myeloma activity</p>

<p>Inhibits JAK1 and JAK2 kinases</p>

<p>Phosphorylated EGFR peptide substrate.</p>

<p>Amlodipine is a calcium channel blocker that is used to treat hypertension and angina. This drug inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle.</p>

<p>Roflumilast is a selective phosphodiesterase-4 inhibitor that is used for the treatment of exacerbations in patients with chronic obstructive pulmonary disease (COPD). It is also used to treat plaque psoriasis. This drug has anti-inflammatory and immunomodulatory effects as it aids in increasing levels of cAMP.</p>

<p>Potent inverse agonist of peroxisome proliferator-activated receptor PPARβ and PPARδ with IC50 value of 27 nM. In mouse myoblasts, DG 172 enhanced recruitment of transcriptional corepressor and down-regulated transcription of PPARβ/δ target gene Angptl4. DG 172 also possess a PPARβ/δ-independent activity on bone marrow cells and promotes dendritic cell differentiation.</p>

<p>Amino acids 651-660 of Poly(ADP-ribose) polymerase 1 (PARP1). PARP1 is a nuclear DNA repair enzyme that binds to DNA when damage is detected. PARP1 coordinates double and single strand break repair by first cleaving NAD+ into nicotinamide and ADP-ribose, and then synthesising poly-(ADP-ribose) (PAR) chains from ADP-ribose on target proteins (PARylation). PARylation of histone proteins mediates the relaxation of the chromatin and recruitment of DNA-break repair enzymes.PARP1 can also act as a transcriptional co-activator, modulating the expression of itself and many other genes by direct binding to or PARylation of enhancers and promoters. PARP1 is also involved in maintaining mtDNA.PARP1 belongs to the PARP family which has 7 known and 10 putative members. PARP1 accounts for &gt;85% of the PARP activity in cellular systems.</p>

<p>Receptor tyrosine kinase inhibitor; anti-angiogenesis; anti-oncogenesis</p>

<p>NMDA glutamate receptor antagonist; anti-depressant</p>