Tìm theo
Chlorambucil
Các tên gọi khác (12 ) :
  • 4-(P-Bis(beta-chloroethyl)aminophenyl)butyric acid
  • 4-(p-bis(β-chloroethyl)aminophenyl)butyric acid
  • 4-[p-[bis(2-chloroethyl)amino]phenyl]butyric acid
  • Ambochlorin
  • CHLORAMBUCIL
  • Chloraminophen
  • gamma-[P-Di(2-chloroethyl)aminophenyl]butyric acid
  • Leukeran
  • N,N-Di-2-chloroethyl-gamma-P-aminophenylbutyric acid
  • N,N-di-2-chloroethyl-γ-p-aminophenylbutyric acid
  • Phenylbutyric Acid Nitrogen Mustard
  • γ-[p-di(2-chloroethyl)aminophenyl]butyric acid
Thuốc điều trị ung thư
Thuốc Gốc
Small Molecule
CAS: 305-03-3
ATC: L01AA02
ĐG : Excella GmbH , http://www.excella-pharma-source.de
CTHH: C14H19Cl2NO2
PTK: 304.212
A nitrogen mustard alkylating agent used as antineoplastic agent for the treatment of various malignant and nonmalignant diseases. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed)
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C14H19Cl2NO2
Phân tử khối
304.212
Monoisotopic mass
303.079284271
InChI
InChI=1S/C14H19Cl2NO2/c15-8-10-17(11-9-16)13-6-4-12(5-7-13)2-1-3-14(18)19/h4-7H,1-3,8-11H2,(H,18,19)
InChI Key
InChIKey=JCKYGMPEJWAADB-UHFFFAOYSA-N
IUPAC Name
4-{4-[bis(2-chloroethyl)amino]phenyl}butanoic acid
Traditional IUPAC Name
chlorambucil
SMILES
OC(=O)CCCC1=CC=C(C=C1)N(CCCl)CCCl
Độ tan chảy
65 °C
Độ hòa tan
1.24E+004 mg/L
logP
1.70
logS
-3.6
pKa (strongest acidic)
4.46
pKa (Strongest Basic)
1.72
PSA
40.54 Å2
Refractivity
79.68 m3·mol-1
Polarizability
31.98 Å3
Rotatable Bond Count
9
H Bond Acceptor Count
3
H Bond Donor Count
1
Physiological Charge
-1
Number of Rings
1
Bioavailability
1
Rule of Five
true
Ghose Filter
true
pKa
5.75
Dược Lực Học : Chlorambucil is an antineoplastic in the class of alkylating agents that is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
Cơ Chế Tác Dụng : A nitrogen mustard alkylating agent used as antineoplastic agent for the treatment of various malignant and nonmalignant diseases. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed) Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.
Dược Động Học :

▧ Protein binding :
99%
▧ Route of Elimination :
Chlorambucil is extensively metabolized in the liver primarily to phenylacetic acid mustard. The pharmacokinetic data suggests that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance and that it is almost completely metabolized, having extremely low urinary excretion.
▧ Half Life :
1.5 hours
Chỉ Định : For treatment of chronic lymphatic (lymphocytic) leukemia, childhood minimal-change nephrotic syndrome, and malignant lymphomas including lymphosarcoma, giant follicular lymphoma, Hodgkin's disease, non-Hodgkin's lymphomas, and Waldenström’s Macroglobulinemia.
Tương Tác Thuốc :
  • Bendamustine Increases toxicity through pharmacodynamic synergism. Additive myelosuppression.
  • Leflunomide Immunosuppressants such as chlorambucil may enhance the adverse/toxic effect of leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity. Also, patients receiving both leflunomide and another immunosuppressive medication should be monitored for bone marrow suppression at least monthly throughout the duration of concurrent therapy.
  • Natalizumab Immunosuppressants such as chlorambucil may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
  • Pimecrolimus Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as chlorambucil. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
  • Roflumilast Roflumilast may enhance the immunosuppressive effect of immunosuppressants such as chlorambucil. The Canadian roflumilast product monograph recommends avoiding concurrent use of roflumilast with any immunosuppressant medications due to the antiinflammatory/immune altering effects of roflumilast and the lack of relevant clinical experience with such use. Of note, this recommendation to avoid concurrent use does not apply to either inhaled corticosteroids (which have much more limited systemic immune-suppressing actions) or short-term systemic corticosteroid use. U.S. prescribing information does not contain this warning; but it appears prudent to avoid this combination when possible.
  • Tacrolimus Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants sucb as chlorambucil. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Liều Lượng & Cách Dùng : Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Leukeran 2 mg tablet
    Giá bán buôn : USD >3.92
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty : Celon
    Sản phẩm biệt dược : Celkeran
  • Công ty : Techni-Pharma
    Sản phẩm biệt dược : Chloraminophène
  • Công ty : GlaxoSmithKline
    Sản phẩm biệt dược : Leukeran
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00291
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2708
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506842
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00266
ChemSpider
http://www.chemspider.com/Chemical-Structure.2607.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0173-0635-35
PharmGKB
http://www.pharmgkb.org/drug/PA448926
Wikipedia
http://en.wikipedia.org/wiki/Chlorambucil
RxList
http://www.rxlist.com/cgi/generic2/leukeran.htm
Drugs.com
http://www.drugs.com/cdi/chlorambucil.html
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