Tìm theo
Ruxolitinib
Các tên gọi khác (2) :
  • INCB018424
  • INCB424
Thuốc Gốc
Small Molecule
CAS: 941678-49-5
ATC: L01XE18
CTHH: C17H18N6
PTK: 306.365
Ruxolitinib is a janus-associated kinase inhibitor indicated to treat bone marrow cancer, specifically intermediate or high-risk myelofibrosis. FDA approved on November 16, 2011.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C17H18N6
Phân tử khối
306.365
Monoisotopic mass
306.159294606
InChI
InChI=1S/C17H18N6/c18-7-5-15(12-3-1-2-4-12)23-10-13(9-22-23)16-14-6-8-19-17(14)21-11-20-16/h6,8-12,15H,1-5H2,(H,19,20,21)/t15-/m1/s1
InChI Key
InChIKey=HFNKQEVNSGCOJV-OAHLLOKOSA-N
IUPAC Name
(3R)-3-cyclopentyl-3-(4-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}-1H-pyrazol-1-yl)propanenitrile
Traditional IUPAC Name
(3R)-3-cyclopentyl-3-(4-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}pyrazol-1-yl)propanenitrile
SMILES
N#CC[C@H](C1CCCC1)N1C=C(C=N1)C1=C2C=CNC2=NC=N1
Độ hòa tan
Soluble in aqueous buffers across a pH of 1-8
logP
2.48
logS
-3.4
pKa (strongest acidic)
13.89
pKa (Strongest Basic)
5.51
PSA
83.18 Å2
Refractivity
98.01 m3·mol-1
Polarizability
33.04 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
4
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : The mean half-maximal inhibitory concentration (IC50) for JAK 1 and JAK 2 are 2.8 nmol/L and 3.3 nmol/L respectively. After administration of ruxolitinib, a decrease in levels of phosphorylated STAT (marker for JAK activity) in a dose-dependent manner can be observed. Pharmacodynamic resistance has not been observed.
Cơ Chế Tác Dụng : Ruxolitinib is a janus-associated kinase inhibitor indicated to treat bone marrow cancer, specifically intermediate or high-risk myelofibrosis. FDA approved on November 16, 2011. Ruxolitinib is a kinase inhibitor that is selective for the Janus Associated Kinases (JAK) 1 and 2. These kinases are responsible for the mediation of cytokine and growth factor signalling which in turn effect immune function and hematopoiesis. The signalling process involves signal transducers and transcription activators (STAT) which modulate gene expression. Patients with myelofibrosis have abnormal JAK1 and JAK2 activity thus ruxolitinib works to regulate this.
Dược Động Học :
▧ Absorption :
Absorption is rapid and is not affected by food. Cmax, 15 mg, healthy subject = 649 nmol/L; Tmax, 15 mg, healthy subject = 1.5 hours; Ruxolitinib does not accumulate significantly.
▧ Volume of Distribution :
Terminal phase volume of distribution, 15 mg, healthy subject = 76.6 L.
▧ Protein binding :
97% protein bound, primarily to albumin.
▧ Metabolism :
Ruxolitinib is metabolized by CYP3A4. Less potent active metabolites forms as a result.
▧ Route of Elimination :
Eliminated via urine (74%, <1% as unchanged drug) and feces (22%, <1% as unchanged drug).
▧ Half Life :
Mean elimination half-life, 15 mg, healthy subject = 2.8 hours.
▧ Clearance :
15 mg, healthy subject = 18.7 L/h.
Độc Tính : Thrombocytopenia was the dose-limiting toxicity.
Chỉ Định : Treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocythemia (post-ET) myelofibrosis. [Lexicomp] Myeolofibrosis is the proliferation of abnormal bone marrow stem cells which cause fibrosis (the excessive formation of connective tissue).
Tương Tác Thuốc :
  • Itraconazole Strong CYP3A4 inhibitors may increase levels of ruxolitinib. Consider alternate therapy.
  • Ketoconazole Strong CYP3A4 inhibitors may increase levels of ruxolitinib. Consider alternate therapy.
  • Rifampicin Strong CYP3A4 inducers may decrease levels of ruxolitinib. Closely monitor patient.
  • Voriconazole Strong CYP3A4 inhibitors may increase levels of ruxolitinib. Consider alternate therapy.
Liều Lượng & Cách Dùng : Tablet - Oral - 5 mg, 10 mg, 15 mg, 20 mg, 25 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08877
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D09959
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/50881-025-60
Wikipedia
http://en.wikipedia.org/wiki/Ruxolitinib
RxList
http://www.rxlist.com/jakafi-drug.htm
Drugs.com
http://www.drugs.com/mtm/ruxolitinib.html
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