Description
Key facts
CAS number:1051375-16-6,
Form:SolidSee storage information,
Molecular weight:419.4 Da,
Molecular formula:C20H19F2N3O5,
PubChem:54726191,
Nature:Synthetic,
Solubility:Soluble in DMSO to 5mM.,
Biochemical name:Dolutegravir,
Biological description:Potent HIV integrase inhibitor (IC50 = 2.7 nM for HIV-1 integrase-catalyzed strand transfer in vitro). Inhibits HIV-1 viral replication (EC50 = 0.51 nM) in peripheral blood mononuclear cells (PBMCs). Prevents replication of several HIV-1 strains (EC50 values of 0.36-2.1 nM) that are resistant to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors.,
Canonical smiles:CC1CCOC2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O,
Isomeric smiles:C[C@@H]1CCO[C@@H]2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O,
InChi:InChI=1S/C20H19F2N3O5/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28)/t10-,15+/m1/s1,
InChiKey:RHWKPHLQXYSBKR-BMIGLBTASA-N,
IUPAC Name:(3S,7R)-N-[(2,4-difluorophenyl)methyl]-11-hydroxy-7-methyl-9,12-dioxo-4-oxa-1,8-diazatricyclo[8.4.0.03,8]tetradeca-10,13-diene-13-carboxamide
Properties and Storage Information:
Shipped at conditions-Blue Ice, Appropriate short-term storage conditions--20°C, Appropriate long-term storage conditions--20°C
Supplementary Information:
This supplementary information is collated from multiple sources and compiled automatically.
Cytochrome P450 3A4 also known as CYP3A4 is a member of the cytochrome P450 family of enzymes. It is a versatile monooxygenase with a mass of about 57 kDa. One can find CYP3A4 abundantly expressed in the liver and intestinal mucosa playing a critical role in metabolizing a wide range of xenobiotics and endogenous compounds. Vesicular acetylcholine transporter (VAChT) a membrane protein responsible for transporting acetylcholine into synaptic vesicles and Sigma1-receptor a chaperone protein located in the endoplasmic reticulum are two key players within the cellular environment. UDP-glucuronosyltransferase 1A1 (UGT1A1) is primarily involved in the glucuronidation process contributing significantly to the detoxification and metabolization pathways.
Biological function summary
CYP3A4 is important in metabolizing nearly 50% of all drugs including integrase inhibitors like dolutegravir used in HIV therapy. This enzyme mediates the oxidative metabolism impacting drug absorption and clearance rates. VAChT facilitates synaptic transmission by packaging acetylcholine while Sigma1-receptor is involved in cell signaling and stress response modulation. UGT1A1 is essential in bilirubin clearance and metabolizing various xenobiotics and endogenous substances. These targets are not part of a singular complex but exhibit essential roles individually within their respective pathways.
Pathways
These proteins perform integral roles in different biological functions. CYP3A4 is central in the drug metabolism pathway alongside other CYPs influencing the pharmacokinetics of many medications. VAChT is involved in cholinergic neurotransmission critical for nerve signal propagation. Similarly Sigma1-receptor is part of the neuroprotective and apoptotic pathways related to calcium signaling and lipid transport. UGT1A1 is prominently featured in the glucuronidation pathway a phase II drug metabolism process closely linked with heme and bilirubin metabolism. These proteins have specific yet interconnected pathways functioning with various related proteins.
CYP3A4's activity significantly affects treatment outcomes in patients with HIV given its role in metabolizing most antiretroviral drugs including dolutegravir - an integrase inhibitor. Variations in CYP3A4 activity can lead to alterations in drug efficacy and toxicity intersecting with proteins involved in hepatic metabolism. VAChT dysfunction is associated with neurological disorders such as Alzheimer's disease impacting neurotransmitter regulation. Sigma1-receptor is implicated in neurodegenerative diseases like Amyotrophic Lateral Sclerosis (ALS) due to its role in neuroprotection while UGT1A1 is directly involved in conditions like Gilbert's syndrome affecting bilirubin conjugation. These proteins contribute to disease mechanisms highlighting their importance in therapeutic contexts.
