Tìm theo
Homoharringtonine
Các tên gọi khác (5 ) :
  • Cephalotaxus alkaloid
  • CGX-635
  • HHT
  • Myelostat
  • omacetaxine mepesuccinate
Thuốc điều trị ung thư
Thuốc Gốc
Small Molecule
CAS: 26833-87-4
ATC: L01XX40
CTHH: C29H39NO9
PTK: 545.6213
Homoharringtonine, AKA HHT or omacetaxine mepesuccinate, is a cephalotaxine ester and protein synthesis inhibitor with established clinical activity as a single agent in hematological malignancies. Homoharringtonine is synthesized from cephalotaxine, which is an extract from the leaves of the plant, Cephalotaxus species. In October 2005, homoharringtonine received Orphan Drug designation from the EMEA for the treatment of chronic myeloid leukemia (CML). Then in March 2006, homoharringtonine received Orphan Drug status from the FDA for the treatment of CML. In November 2006, homoharringtonine, for the treatment of CML, was granted Fast Track designation by the FDA. Most recently, in October 2012, homoharringtonine was marketed under the brand name Synribo™ and FDA approved for patients who are intolerant and/or resistant to two or more tyrosine kinase inhibitors used to treat accelerated or chronic phase CML.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C29H39NO9
Phân tử khối
545.6213
Monoisotopic mass
545.262481851
InChI
InChI=1S/C29H39NO9/c1-27(2,33)8-5-10-29(34,16-23(31)36-4)26(32)39-25-22(35-3)15-28-9-6-11-30(28)12-7-18-13-20-21(38-17-37-20)14-19(18)24(25)28/h13-15,24-25,33-34H,5-12,16-17H2,1-4H3/t24-,25+,28-,29?/m0/s1
InChI Key
InChIKey=HYFHYPWGAURHIV-ZEDNPHJLSA-N
IUPAC Name
(2R,3S,6R)-4-methoxy-16,18-dioxa-10-azapentacyclo[11.7.0.0^{2,6}.0^{6,10}.0^{15,19}]icosa-1(13),4,14,19-tetraen-3-yl 1-methyl 3-hydroxy-3-(4-hydroxy-4-methylpentyl)butanedioate
Traditional IUPAC Name
(2R,3S,6R)-4-methoxy-16,18-dioxa-10-azapentacyclo[11.7.0.0^{2,6}.0^{6,10}.0^{15,19}]icosa-1(13),4,14,19-tetraen-3-yl 1-methyl 3-hydroxy-3-(4-hydroxy-4-methylpentyl)butanedioate
SMILES
[H][C@]12[C@H](OC(=O)C(O)(CCCC(C)(C)O)CC(=O)OC)C(OC)=C[C@@]11CCCN1CCC1=CC3=C(OCO3)C=C21
Độ hòa tan
1.08e-01 g/l
logP
1.88
logS
-3.7
pKa (strongest acidic)
12.09
pKa (Strongest Basic)
9.42
PSA
123.99 Å2
Refractivity
142.07 m3·mol-1
Polarizability
58.05 Å3
Rotatable Bond Count
11
H Bond Acceptor Count
8
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
5
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : The pharmacodynamics of homoharringtonine is not fully understood. It is known that homoharringtonine is involved with protein synthesis inhibition and this leads to its antineoplastic activity.
Cơ Chế Tác Dụng : Homoharringtonine, AKA HHT or omacetaxine mepesuccinate, is a cephalotaxine ester and protein synthesis inhibitor with established clinical activity as a single agent in hematological malignancies. Homoharringtonine is synthesized from cephalotaxine, which is an extract from the leaves of the plant, Cephalotaxus species. In October 2005, homoharringtonine received Orphan Drug designation from the EMEA for the treatment of chronic myeloid leukemia (CML). Then in March 2006, homoharringtonine received Orphan Drug status from the FDA for the treatment of CML. In November 2006, homoharringtonine, for the treatment of CML, was granted Fast Track designation by the FDA. Most recently, in October 2012, homoharringtonine was marketed under the brand name Synribo™ and FDA approved for patients who are intolerant and/or resistant to two or more tyrosine kinase inhibitors used to treat accelerated or chronic phase CML. Homoharringtonine inhibits protein synthesis by not directly binding to Bcr-Abl. It binds to the A-site cleft in the large ribosomal subunit, which affects chain elongation and prevents protein synthesis.
Dược Động Học :
▧ Absorption :
Homoharringtonine absorption was not quantified, but maximum concentration is reached after about 30 mins.
▧ Volume of Distribution :
Homoharringtonine has a steady state Vd of 141 ± 93.4 L.
▧ Protein binding :
Plasma protein binding is equal or less than 50%.
▧ Metabolism :
Homoharringtonine has undergoes little hepatic metabolism and is mostly metabolized to 4’-DMHHT by plasma esterase hydrolysis.
▧ Route of Elimination :
The main route of elimination for homoharringtonine is still unknown, but renal elimination is less than 15%.
▧ Half Life :
Homoharringtonine has a half life of about 6 hours after subcutaneous administration.
▧ Clearance :
Clearance for homoharringtonine was not quantified.
Độc Tính : The most severe adverse effects after homoharringtonine administration are myelosuppression, bleeding, hyperglycemia, and fetal harm.
Chỉ Định : Used in patients who are intolerant and/or resistant to two or more tyrosine kinase inhibitors used to treat accelerated or chronic phase CML.
Tương Tác Thuốc :
  • Acetylsalicylic acid Avoid combination with acetylsalicylic acid due to the potential enhancement of homoharringtonine associated bleeding-related adverse effects. Specifically it is suggested to avoid this combination in patients with a platelet count of less than 50,000/uL.
  • Ibuprofen Avoid combination with ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) due to the potential enhancement of homoharringtonine associated bleeding-related adverse effects. Specifically it is suggested to avoid this combination in patients with a platelet count of less than 50,000/uL.
  • Natalizumab Avoid combination due to the increased risk of infection.
  • Pimecrolimus Avoid combination as there is potential to increase immunosuppressant adverse effects.
  • Tacrolimus Avoid combination as there is potential to increase immunosuppressant adverse effects.
  • Tofacitinib Avoid combination with tofacitinib and other potent immunosuppressants as there is potential to increase the immunosuppressant effects. Other less potent immunosuppressants such as methotrexate, at antirheumatic doses, and other non-disease modifying antirheumatic drugs (non-DMARDs) can be combined.
  • Warfarin Avoid combination with warfarin and other anticoagulants due to the potential enhancement of homoharringtonine associated bleeding-related adverse effects. Specifically it is suggested to avoid this combination in patients with a platelet count of less than 50,000/uL.
Liều Lượng & Cách Dùng : Powder - Subcutaneous - 3.5MG/VIAL
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB04865
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=72332
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=11075063
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D08956
ChemSpider
http://www.chemspider.com/Chemical-Structure.65276.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/63459-177-14
Wikipedia
http://en.wikipedia.org/wiki/Omacetaxine_mepesuccinate
RxList
http://www.rxlist.com/synribo-drug.htm
Drugs.com
http://www.drugs.com/cdi/omacetaxine-injection.html
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