Megestrol acetate appears to be completely metabolized in the liver to free steroids and glucuronide conjugates of 17alpha-acetoxy-2alpha-hydroxy-6-methylpregna-4,6-diene-3,20-dione, 17alpha-acetoxy-6-hydroxymethylpregna-4,6-diene-3,20-dione, and 17alpha-acetoxy-2alpha-hydroxy-6-hydroxymethylpregna-4,6-diene-3,20-dione.
Completely metabolized in liver to free steroids and glucuronide conjugates of 17alpha-acetoxy-2alpha-hydroxy-6-methylpregna-4,6-diene-3,20-dione, 17alpha-acetoxy-6-hydroxymethylpregna-4,6-diene-3,20-dione, & 17alpha-acetoxy-2alpha-hydroxy-6-hydroxymethylpregna-4,6-diene-3,20-dione /Human, oral/
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
Megestrol acetate appears to be well absorbed from the GI tract. The relative oral bioavailability of megestrol acetate suspensions and tablets has not been evaluated.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
使用更浓缩的口服悬浮液（Megace ES 625 mg/5 mL）625毫克剂量的情况下达到的血浆醋酸甲地孕酮浓度，在进食条件下与原始配方（200 mg/5 mL）800毫克剂量达到的浓度相当。
Plasma megestrol acetate concentrations achieved with a 625-mg dose of the more concentrated oral suspension (Megace ES 625 mg/5 mL) are equivalent to those achieved with an 800-mg dose of the original formulation (200 mg/5 mL) under fed conditions.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
醋酸甲羟孕酮口服悬浮液的生物利用度受食物影响的情况尚未评估。
The effect of food on the bioavailability of Megestrol Acetate Oral Suspension has not been evaluated.
Peak concentrations and AUC were 54.8 and 43.3% higher, respectively, under fed conditions compared with fasting for the concentrated suspension and were 12.9 and 24.4% higher, respectively, under fed conditions compared with fasting for the original formulation.
[EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
申请人：GILEAD APOLLO LLC
公开号：WO2017075056A1
公开（公告）日：2017-05-04
The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an anti-tumor drug via a cleavable linker and one or more optional spacers. Cobalamin is covalently bound to a first spacer or the cleavable linker via the 5′-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.
[EN] DIHYDROPYRROLONAPHTYRIDINONE COMPOUNDS AS INHIBITORS OF JAK<br/>[FR] COMPOSÉS DE DIHYDROPYRROLONAPHTYRIDINONE COMME INHIBITEURS DE JAK
申请人：TAKEDA PHARMACEUTICAL
公开号：WO2010144486A1
公开（公告）日：2010-12-16
Disclosed are JAK inhibitors of formula (I) where G1, R1, R2, R3, R4, R5, R6, and R7 are defined in the specification. Also disclosed are pharmaceutical compositions, kits and articles of manufacture which contain the compounds, methods and materials for making the compounds, and methods of using the compounds to treat diseases, disorders, and conditions involving the immune system and inflammation, including rheumatoid arthritis, hematological malignancies, epithelial cancers (i.e., carcinomas), and other diseases, disorders or conditions associated with JAK.
[EN] COMPOUNDS AND METHODS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
申请人：TAVARES FRANCIS XAVIER
公开号：WO2016168118A1
公开（公告）日：2016-10-20
Novel compounds of formula (II) are disclosed. Compounds of formula (II) comprise ornithine derivatives or compounds that may metabolize to ornithine. Also disclosed are methods for the treatment of neurodegenerative diseases such as Alzheimer's Disease using compounds of formula (II).
[EN] COMPOUNDS AS MODULATORS OF TIGIT SIGNALLING PATHWAY<br/>[FR] COMPOSÉS MODULATEURS DE LA VOIE DE SIGNALISATION DE TIGIT
申请人：AURIGENE DISCOVERY TECH LTD
公开号：WO2018047139A1
公开（公告）日：2018-03-15
The present invention relates to compound of formula (I) as therapeutic agents to modulate the TIGIT signalling pathway. The invention also encompasses the use of the compound of formula (I) or a stereoisomer thereof or a pharmaceutically acceptable salt thereof for the treatment of diseases or disorders mediated by TIGIT.
