Tìm theo
Enzalutamide
Các tên gọi khác (4 ) :
  • MDV 3100
  • MDV-3100
  • MDV3100
  • XTANDI
Thuốc điều trị ung thư
Thuốc Gốc
Small Molecule
CAS: 915087-33-1
CTHH: C21H16F4N4O2S
PTK: 464.436
Enzalutamide is an androgen receptor inhibitor for the treatment of castration-resistant prostate cancer. FDA approved on August 31, 2012.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C21H16F4N4O2S
Phân tử khối
464.436
Monoisotopic mass
464.093009286
InChI
InChI=1S/C21H16F4N4O2S/c1-20(2)18(31)28(12-5-4-11(10-26)15(8-12)21(23,24)25)19(32)29(20)13-6-7-14(16(22)9-13)17(30)27-3/h4-9H,1-3H3,(H,27,30)
InChI Key
InChIKey=WXCXUHSOUPDCQV-UHFFFAOYSA-N
IUPAC Name
4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-2-fluoro-N-methylbenzamide
Traditional IUPAC Name
4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-2-fluoro-N-methylbenzamide
SMILES
CNC(=O)C1=C(F)C=C(C=C1)N1C(=S)N(C(=O)C1(C)C)C1=CC=C(C#N)C(=C1)C(F)(F)F
Độ hòa tan
Insoluble
logP
4.16
logS
-5.5
pKa (strongest acidic)
13.05
pKa (Strongest Basic)
-1.7
PSA
76.44 Å2
Refractivity
113.48 m3·mol-1
Polarizability
42.71 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
3
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Resitance to enzalutamide therapy has been observed. This may occurred due to an upregulation of NF-κB2/p52.
Cơ Chế Tác Dụng : Enzalutamide is an androgen receptor inhibitor for the treatment of castration-resistant prostate cancer. FDA approved on August 31, 2012. Enzalutamide is a competitive androgen receptor inhibitor that effects multiple stages of the signalling pathway. It is able to inhibit androgen binding to its receptor, androgen receptor nuclear translocation, and subsequent interaction with DNA. As a result, proliferation of prostate cancer cells decreases which ultimately leads to apoptosis and decreased tumour volume.
Dược Động Học :
▧ Absorption :
The pharmacokinetic profile of enzalutamide and N-desmethyl enzalutamide (its major active metabolite) is described by a linear two-compartment model with first-order absorption. Enzalutamide also accumulates. Food does not affect its absorption. Tmax, prostate cancer patients = 1 hour (range of 0.5-3 hours); Cmax, steady state, enzalutamide = 16.6 μg/mL; Cmax, steady state, N-desmethyl enzalutamide = 12.7 μg/mL; Time to steady state, daily dosing = 28 days;
▧ Volume of Distribution :
Apparent volume of distribution (Vd/F), single oral dose = 110 L
▧ Protein binding :
Enzalutamide is 97% to 98% bound to plasma proteins, primarily albumin. N-desmethyl enzalutamide is 95% bound to plasma proteins.
▧ Metabolism :
Enzalutamide is hepatically metabolized, primarily by CYP2C8 and CYP3A4. The enzyme that converts enzalutamide to its active metabolite, N-desmethyl enzalutamide, is CYP2C8. The activity of N-desmethyl-enzalutamide is similar to that of the parent compound.
▧ Route of Elimination :
Enzalutamide is primarily eliminated by hepatic metabolism. 71% of the dose is recovered in urine (including only trace amounts of enzalutamide and N-desmethyl enzalutamide), and 14% is recovered in feces (0.4% of dose as unchanged enzalutamide and 1% as N-desmethyl enzalutamide).
▧ Half Life :
The mean terminal half-life (t1/2) for enzalutamide in patients after a single oral dose is 5.8 days (range 2.8 to 10.2 days). Following a single 160 mg oral dose of enzalutamide in healthy volunteers, the mean terminal t1/2 for N-desmethyl enzalutamide is approximately 7.8 to 8.6 days.
▧ Clearance :
Apparent clearance (CL/F), single oral dose = 0.56 L/h (range of 0.33 - 1.02 L/h)
Độc Tính : The most common adverse reactions (≥ 5%) are asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension.
Chỉ Định : Enzalutamide is indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.
Liều Lượng & Cách Dùng : Capsule - Oral - 40 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08899
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D10218
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0469-0125-99
Wikipedia
http://en.wikipedia.org/wiki/Enzalutamide
RxList
http://www.rxlist.com/xtandi-drug.htm
Drugs.com
http://www.drugs.com/cdi/enzalutamide.html
... loading
... loading