After oral administration of a 0.48 mcg/kg dose of 3 H-paricalcitol, parent drug was extensively metabolized, with only about 2% of the dose eliminated unchanged in the feces, and no parent drug found in the urine. Several metabolites were detected in both the urine and feces. Most of the systemic exposure was from the parent drug. Two minor metabolites, relative to paricalcitol, were detected in human plasma. One metabolite was identified as 24(R)-hydroxy paricalcitol, while the other metabolite was unidentified. The 24(R)-hydroxy paricalcitol is less active than paricalcitol in an in vivo rat model of PTH suppression.
In vitro data suggest that paricalcitol is metabolized by multiple hepatic and non-hepatic enzymes, including mitochondrial CYP24, as well as CYP3A4 and UGT1A4. The identified metabolites include the product of 24(R)-hydroxylation, 24,26- and 24,28-dihydroxylation and direct glucuronidation.
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
[EN] PYRAZOLOPYRIDINE DERIVATIVES FOR THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE PYRAZOLOPYRIDINE POUR LE TRAITEMENT DU CANCER
申请人：GENENTECH INC
公开号：WO2017205538A1
公开（公告）日：2017-11-30
The present invention relates to a compound formula (I): and to salts thereof, wherein R1, R2X, and Y have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders such as cancer, inflammatory disorders and autoimmune diseases.
[EN] SULFONAMIDE COMPOUNDS AND USES AS TNAP INHIBITORS<br/>[FR] COMPOSÉS SULFONAMIDES ET LEURS UTILISATIONS EN TANT QU'INHIBITEURS DE TNAP
申请人：SANFORD BURNHAM MED RES INST
公开号：WO2013126608A1
公开（公告）日：2013-08-29
Described herein are compounds that modulate the activity of TNAP. In some embodiments, the compounds described herein inhibit TNAP. In certain embodiments, the compounds described herein are useful in the treatment of conditions associated with hyper- mineralization.
[EN] BIOREVERSABLE PROMOIETIES FOR NITROGEN-CONTAINING AND HYDROXYL-CONTAINING DRUGS<br/>[FR] PRO-FRAGMENTS BIORÉVERSIBLES POUR MÉDICAMENTS CONTENANT DE L'AZOTE ET DE L'HYDROXYLE
申请人：BAIKANG SUZHOU CO LTD
公开号：WO2015081891A1
公开（公告）日：2015-06-11
Disclosed are promoieties of the following formula which can be used to form prodrugs of nitrogen-containing or hydroxyl-containing drug or a pharmaceutically active agent: (I) and pharmaceutical compositions comprising the prodrugs.
[EN] THERAPEUTIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS THÉRAPEUTIQUES ET LEURS UTILISATIONS
申请人：GENENTECH INC
公开号：WO2016123391A1
公开（公告）日：2016-08-04
The present invention relates to compounds of formula (I): and to salts thereof, wherein R1-R6 have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of TAF1. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various TAF1-mediated disorders.
Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula Ia,
as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
