アベマシクリブ 化學(xué)特性,用途語,生産方法
効能
抗悪性腫瘍薬, サイクリン依存性キナーゼ(CDK)阻害薬
商品名
ベージニオ (日本イーライリリー)
特性
Class: serine/threonine protein kinase
Treatment: Breast cancer
Oral bioavailability = 46%
Elimination half-life = 18 h
Protein binding = 95–98%
Biochem/physiol Actions
LY2835219 (abemaciclib) was identified via compound and biochemical screening by scientists at Eli Lilly and Company Research Laboratories and selected for its biological activity and highly selective inhibition of the complexes CDK4/ cyclin D1 (IC50 =2 nmol/L) and CDK6/cyclin D1 (IC50 =10 nmol/L), with no activity against other CDK/cyclin complexes or cell-cycle-related kinases within the nanomolar ranges, except for inhibition of CDK9 at IC50 at least five times higher. The compound was shown to act as a competitive inhibitor of the ATP-binding domain of the CDK4 and CDK6 and to be 14 times more potent against CDK4 than against CDK6. In comparison to palbociclib and ribociclib, abemaciclib shows higher selectivity for the complex CDK4/cyclin D1, with IC50 values five times lower than those of the two other compounds[1].
副作用
Common side effects of abemaciclib include: gastrointestinal reactions (diarrhea, loss of appetite, nausea, vomiting, stomach pain and constipation); increased risk of infection (main symptoms include changes in body temperature, muscle aches, cough, headache, feeling cold and shivering, pain or burning when urinating); skin problems (rash, itchy and dry skin); bruises, bleeding gums or nosebleeds; difficulty breathing, paleness, taste changes, mouth pain, tiredness and weakness; hair loss. Serious side effects are fatal interstitial lung disease. In addition, abemaciclib can cause thrombotic coronary artery side effects when treating advanced breast cancer.
酵素阻害剤
This oral cell cycle inhibitor (FWfree-base = 506.61 g/mol; FWmesylate-salt =
602.70 g/mol; CAS 1231930-82-7 (mesylate salt) ), also known as
LY2835219 and N-[5-[ (4-ethyl-1-piperazinyl) methyl]-2-pyridinyl]-5-
fluoro-4-[4-fluoro-2-methyl-1- (1-methylethyl) -1H-benzimidazol-6-yl]-2-
pyrimidinamine, targets the cyclin-dependent kinase CDK4, or cyclin D1
(IC50 = 2 nM) and CDK6, or cyclin D3 (IC50 = 6 nM), inhibiting
retinoblastoma (Rb) protein phosphorylation in early G1, thereby arresting
the cell cycle in the G1, suppressing DNA synthesis, and inhibiting cancer
cell growth. LY2835219 inhibits activation of AKT and ERK, but not
mTOR.
アベマシクリブ 上流と下流の製品情報
原材料
EthaniMidaMide, N-(4-broMo-2,6-difluorophenyl)-N'-(1-Methylethyl)-
4-ブロモ-2,6-ジフルオロアニリン
2-ブロモ-5-ピリジンカルボキシアルデヒド 臭化物
1-((6-ブロモピリジン-3-イル)メチル)-4-エチルピペラジン
N-イソプロピルアセトアミド
6-(2-クロロ-5-フルオロピリミジン-4-イル)-4-フルオロ-1-イソプロピル-2-メチル-1H-ベンゾ[D]イミダゾール
1H-ベンズイミダゾール, 4-フルオロ-2-メチル-1-(1-メチルエチル)-6-(4,4,5,5-テトラメチル-1,3,2-ジオキサボロラン-2-イル)-
1-(4-アミノ-3,5-ジフルオロフェニル)エタノン
5-((4-エチルピペラジン-1-イル)メチル)ピリジン-2-アミン
6-ブロモ-4-フルオロ-1-イソプロピル-2-メチル-1H-ベンゾ[D]イミダゾール
1-エチルピペラジン
2,6-ジフルオロアニリン
準(zhǔn)備製品