Omacetaxine mepesuccinate
Identification
- Name
- Omacetaxine mepesuccinate
- Accession Number
- DB04865
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
Omacetaxine mepesuccinate (formerly known as HHT or Homoharringtonine), is a cephalotaxine ester and protein synthesis inhibitor with established clinical activity as a single agent in hematological malignancies. Omacetaxine mepesuccinate is synthesized from cephalotaxine, which is an extract from the leaves of the plant, Cephalotaxus species. In October 2005, omacetaxine mepesuccinate received Orphan Drug designation from the EMEA for the treatment of chronic myeloid leukemia (CML). Then in March 2006, it received Orphan Drug status from the FDA for the treatment of CML. In November 2006, omacetaxine mepesuccinate, for the treatment of CML, was granted Fast Track designation by the FDA. Most recently, in October 2012, omacetaxine mepesuccinate 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.
- Structure
- Synonyms
- (−)-homoharringtonine
- (2'R,3S,4S,5R)-(−)-homoharringtonine
- HHT
- Homoharringtonin
- Homoharringtonine
- External IDs
- CGX-635 / NSC-141633
- Product Ingredients
Ingredient UNII CAS InChI Key Omacetaxine mepesuccinate hydrochloride 563OX5661H 457895-79-3 RRNSZQVHVKGKOS-CALFFDBBSA-N - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Synribo Injection, powder, lyophilized, for solution 3.5 mg/mL Subcutaneous Cephalon 2012-11-19 Not applicable US - International/Other Brands
- Ceflatonin (ChemGenex Therapeutics) / Myelostat
- Categories
- UNII
- 6FG8041S5B
- CAS number
- 26833-87-4
- Weight
- Average: 545.6213
Monoisotopic: 545.262481851 - Chemical Formula
- C29H39NO9
- InChI Key
- HYFHYPWGAURHIV-JFIAXGOJSA-N
- 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-/m1/s1
- IUPAC Name
- (2S,3S,6R)-4-methoxy-16,18-dioxa-10-azapentacyclo[11.7.0.0²,⁶.0⁶,¹⁰.0¹⁵,¹⁹]icosa-1(20),4,13,15(19)-tetraen-3-yl 1-methyl (3R)-3-hydroxy-3-(4-hydroxy-4-methylpentyl)butanedioate
- SMILES
- [H][[email protected]@]1(OC(=O)[[email protected]@](O)(CCCC(C)(C)O)CC(=O)OC)C(OC)=C[[email protected]]23CCCN2CCC2=CC4=C(OCO4)C=C2[[email protected]]13[H]
Pharmacology
- Indication
Used in patients who are intolerant and/or resistant to two or more tyrosine kinase inhibitors used to treat accelerated or chronic phase CML.
- Structured Indications
- Pharmacodynamics
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.
- Mechanism of action
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.
Target Actions Organism A50S ribosomal protein L2 antagonistHaloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809) A60S ribosomal protein L3 antagonistHuman - 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.
- Toxicity
The most severe adverse effects after homoharringtonine administration are myelosuppression, bleeding, hyperglycemia, and fetal harm.
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Drug group (4R)-limonene The risk or severity of bleeding can be increased when (4R)-limonene is combined with Omacetaxine mepesuccinate. Investigational Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Omacetaxine mepesuccinate. Approved Aceclofenac The risk or severity of bleeding can be increased when Aceclofenac is combined with Omacetaxine mepesuccinate. Approved, Investigational Acemetacin The risk or severity of bleeding can be increased when Acemetacin is combined with Omacetaxine mepesuccinate. Approved, Experimental, Investigational Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Omacetaxine mepesuccinate. Approved, Investigational Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Approved Acetyldigoxin Acetyldigoxin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Experimental Acetylsalicylic acid The risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Omacetaxine mepesuccinate. Approved, Vet Approved Adapalene The risk or severity of bleeding can be increased when Adapalene is combined with Omacetaxine mepesuccinate. Approved Alclofenac The risk or severity of bleeding can be increased when Alclofenac is combined with Omacetaxine mepesuccinate. Approved, Withdrawn Alminoprofen The risk or severity of bleeding can be increased when Alminoprofen is combined with Omacetaxine mepesuccinate. Experimental Ancestim The risk or severity of cytotoxicity can be increased when Ancestim is combined with Omacetaxine mepesuccinate. Approved, Investigational, Withdrawn Ancrod The risk or severity of bleeding can be increased when Ancrod is combined with Omacetaxine mepesuccinate. Approved, Investigational Andrographolide The risk or severity of bleeding can be increased when Andrographolide is combined with Omacetaxine mepesuccinate. Investigational Anisodamine The risk or severity of bleeding can be increased when Anisodamine is combined with Omacetaxine mepesuccinate. Investigational Antipyrine The risk or severity of bleeding can be increased when Antipyrine is combined with Omacetaxine mepesuccinate. Approved, Investigational Antithrombin III human The risk or severity of bleeding can be increased when Antithrombin III human is combined with Omacetaxine mepesuccinate. Approved Apixaban The risk or severity of bleeding can be increased when Apixaban is combined with Omacetaxine mepesuccinate. Approved Apocynin The risk or severity of bleeding can be increased when Apocynin is combined with Omacetaxine mepesuccinate. Investigational Apremilast The risk or severity of bleeding can be increased when Apremilast is combined with Omacetaxine mepesuccinate. Approved, Investigational Ardeparin The risk or severity of bleeding can be increased when Ardeparin is combined with Omacetaxine mepesuccinate. Approved, Investigational, Withdrawn Argatroban The risk or severity of bleeding can be increased when Argatroban is combined with Omacetaxine mepesuccinate. Approved, Investigational Azapropazone The risk or severity of bleeding can be increased when Azapropazone is combined with Omacetaxine mepesuccinate. Withdrawn Azelastine The risk or severity of bleeding can be increased when Azelastine is combined with Omacetaxine mepesuccinate. Approved Balsalazide The risk or severity of bleeding can be increased when Balsalazide is combined with Omacetaxine mepesuccinate. Approved, Investigational Becaplermin The risk or severity of bleeding can be increased when Becaplermin is combined with Omacetaxine mepesuccinate. Approved, Investigational Bendazac The risk or severity of bleeding can be increased when Bendazac is combined with Omacetaxine mepesuccinate. Experimental Benorilate The risk or severity of bleeding can be increased when Benorilate is combined with Omacetaxine mepesuccinate. Experimental Benoxaprofen The risk or severity of bleeding can be increased when Benoxaprofen is combined with Omacetaxine mepesuccinate. Withdrawn Benzydamine The risk or severity of bleeding can be increased when Benzydamine is combined with Omacetaxine mepesuccinate. Approved Bevacizumab Bevacizumab may increase the cardiotoxic activities of Omacetaxine mepesuccinate. Approved, Investigational Bevonium The risk or severity of bleeding can be increased when Bevonium is combined with Omacetaxine mepesuccinate. Experimental Bivalirudin The risk or severity of bleeding can be increased when Bivalirudin is combined with Omacetaxine mepesuccinate. Approved, Investigational Bromfenac The risk or severity of bleeding can be increased when Bromfenac is combined with Omacetaxine mepesuccinate. Approved Bucillamine The risk or severity of bleeding can be increased when Bucillamine is combined with Omacetaxine mepesuccinate. Investigational Bufexamac The risk or severity of bleeding can be increased when Bufexamac is combined with Omacetaxine mepesuccinate. Approved, Experimental Bumadizone The risk or severity of bleeding can be increased when Bumadizone is combined with Omacetaxine mepesuccinate. Experimental Cabazitaxel The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Omacetaxine mepesuccinate. Approved Carbaspirin calcium The risk or severity of bleeding can be increased when Carbaspirin calcium is combined with Omacetaxine mepesuccinate. Experimental, Investigational Carprofen The risk or severity of bleeding can be increased when Carprofen is combined with Omacetaxine mepesuccinate. Approved, Vet Approved, Withdrawn Castanospermine The risk or severity of bleeding can be increased when Castanospermine is combined with Omacetaxine mepesuccinate. Experimental Celecoxib The risk or severity of bleeding can be increased when Celecoxib is combined with Omacetaxine mepesuccinate. Approved, Investigational Certoparin The risk or severity of bleeding can be increased when Certoparin is combined with Omacetaxine mepesuccinate. Approved, Investigational Chloroquine The risk or severity of bleeding can be increased when Chloroquine is combined with Omacetaxine mepesuccinate. Approved, Investigational, Vet Approved Choline magnesium trisalicylate The risk or severity of bleeding can be increased when Choline magnesium trisalicylate is combined with Omacetaxine mepesuccinate. Approved Citric Acid The risk or severity of bleeding can be increased when Citric Acid is combined with Omacetaxine mepesuccinate. Approved, Nutraceutical, Vet Approved Clonixin The risk or severity of bleeding can be increased when Clonixin is combined with Omacetaxine mepesuccinate. Approved Curcumin The risk or severity of bleeding can be increased when Curcumin is combined with Omacetaxine mepesuccinate. Approved, Investigational Cyclophosphamide Cyclophosphamide may increase the cardiotoxic activities of Omacetaxine mepesuccinate. Approved, Investigational Cymarin Cymarin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Experimental Dabigatran etexilate The risk or severity of bleeding can be increased when Dabigatran etexilate is combined with Omacetaxine mepesuccinate. Approved Dalteparin The risk or severity of bleeding can be increased when Dalteparin is combined with Omacetaxine mepesuccinate. Approved Danaparoid The risk or severity of bleeding can be increased when Danaparoid is combined with Omacetaxine mepesuccinate. Approved, Withdrawn Darexaban The risk or severity of bleeding can be increased when Darexaban is combined with Omacetaxine mepesuccinate. Investigational Desirudin The risk or severity of bleeding can be increased when Desirudin is combined with Omacetaxine mepesuccinate. Approved Deslanoside Deslanoside may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Approved Dextran The risk or severity of bleeding can be increased when Dextran is combined with Omacetaxine mepesuccinate. Approved, Investigational, Vet Approved Dextran 40 The risk or severity of bleeding can be increased when Dextran 40 is combined with Omacetaxine mepesuccinate. Approved Dextran 70 The risk or severity of bleeding can be increased when Dextran 70 is combined with Omacetaxine mepesuccinate. Approved Dextran 75 The risk or severity of bleeding can be increased when Dextran 75 is combined with Omacetaxine mepesuccinate. Approved Diclofenac The risk or severity of bleeding can be increased when Diclofenac is combined with Omacetaxine mepesuccinate. Approved, Vet Approved Dicoumarol The risk or severity of bleeding can be increased when Dicoumarol is combined with Omacetaxine mepesuccinate. Approved Difenpiramide The risk or severity of bleeding can be increased when Difenpiramide is combined with Omacetaxine mepesuccinate. Experimental Diflunisal The risk or severity of bleeding can be increased when Diflunisal is combined with Omacetaxine mepesuccinate. Approved, Investigational Digitoxin Digitoxin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Approved, Investigational Digoxin Digoxin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Approved Digoxin Immune Fab (Ovine) Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Approved Docetaxel The risk or severity of adverse effects can be increased when Docetaxel is combined with Omacetaxine mepesuccinate. Approved, Investigational Droxicam The risk or severity of bleeding can be increased when Droxicam is combined with Omacetaxine mepesuccinate. Withdrawn Duvelisib The risk or severity of bleeding can be increased when Duvelisib is combined with Omacetaxine mepesuccinate. Investigational E-6201 The risk or severity of bleeding can be increased when E-6201 is combined with Omacetaxine mepesuccinate. Investigational Edetic Acid The risk or severity of bleeding can be increased when Edetic Acid is combined with Omacetaxine mepesuccinate. Approved, Vet Approved Edoxaban The risk or severity of bleeding can be increased when Edoxaban is combined with Omacetaxine mepesuccinate. Approved Enoxaparin The risk or severity of bleeding can be increased when Enoxaparin is combined with Omacetaxine mepesuccinate. Approved Epirizole The risk or severity of bleeding can be increased when Epirizole is combined with Omacetaxine mepesuccinate. Approved Etanercept The risk or severity of bleeding can be increased when Etanercept is combined with Omacetaxine mepesuccinate. Approved, Investigational Ethenzamide The risk or severity of bleeding can be increased when Ethenzamide is combined with Omacetaxine mepesuccinate. Experimental Ethyl biscoumacetate The risk or severity of bleeding can be increased when Ethyl biscoumacetate is combined with Omacetaxine mepesuccinate. Withdrawn Etodolac The risk or severity of bleeding can be increased when Etodolac is combined with Omacetaxine mepesuccinate. Approved, Investigational, Vet Approved Etofenamate The risk or severity of bleeding can be increased when Etofenamate is combined with Omacetaxine mepesuccinate. Approved, Investigational Etoricoxib The risk or severity of bleeding can be increased when Etoricoxib is combined with Omacetaxine mepesuccinate. Approved, Investigational Evening primrose oil The risk or severity of bleeding can be increased when Evening primrose oil is combined with Omacetaxine mepesuccinate. Approved, Investigational Exisulind The risk or severity of bleeding can be increased when Exisulind is combined with Omacetaxine mepesuccinate. Investigational Felbinac The risk or severity of bleeding can be increased when Felbinac is combined with Omacetaxine mepesuccinate. Experimental Fenbufen The risk or severity of bleeding can be increased when Fenbufen is combined with Omacetaxine mepesuccinate. Approved Fenoprofen The risk or severity of bleeding can be increased when Fenoprofen is combined with Omacetaxine mepesuccinate. Approved Fentiazac The risk or severity of bleeding can be increased when Fentiazac is combined with Omacetaxine mepesuccinate. Experimental Feprazone The risk or severity of bleeding can be increased when Feprazone is combined with Omacetaxine mepesuccinate. Experimental Ferulic acid The risk or severity of bleeding can be increased when Ferulic acid is combined with Omacetaxine mepesuccinate. Experimental Floctafenine The risk or severity of bleeding can be increased when Floctafenine is combined with Omacetaxine mepesuccinate. Approved, Withdrawn Fluindione The risk or severity of bleeding can be increased when Fluindione is combined with Omacetaxine mepesuccinate. Approved, Investigational Flunixin The risk or severity of bleeding can be increased when Flunixin is combined with Omacetaxine mepesuccinate. Vet Approved Flunoxaprofen The risk or severity of bleeding can be increased when Flunoxaprofen is combined with Omacetaxine mepesuccinate. Experimental Flurbiprofen The risk or severity of bleeding can be increased when Flurbiprofen is combined with Omacetaxine mepesuccinate. Approved, Investigational Fondaparinux The risk or severity of bleeding can be increased when Fondaparinux is combined with Omacetaxine mepesuccinate. Approved, Investigational Fondaparinux sodium The risk or severity of bleeding can be increased when Fondaparinux sodium is combined with Omacetaxine mepesuccinate. Approved, Investigational Gabexate The risk or severity of bleeding can be increased when Gabexate is combined with Omacetaxine mepesuccinate. Investigational Gitoformate Gitoformate may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Experimental Guacetisal The risk or severity of bleeding can be increased when Guacetisal is combined with Omacetaxine mepesuccinate. Experimental Heparin The risk or severity of bleeding can be increased when Heparin is combined with Omacetaxine mepesuccinate. Approved, Investigational Higenamine The risk or severity of bleeding can be increased when Higenamine is combined with Omacetaxine mepesuccinate. Investigational Ibuprofen The risk or severity of bleeding can be increased when Ibuprofen is combined with Omacetaxine mepesuccinate. Approved Ibuproxam The risk or severity of bleeding can be increased when Ibuproxam is combined with Omacetaxine mepesuccinate. Withdrawn Icatibant The risk or severity of bleeding can be increased when Icatibant is combined with Omacetaxine mepesuccinate. Approved, Investigational Idraparinux The risk or severity of bleeding can be increased when Idraparinux is combined with Omacetaxine mepesuccinate. Investigational Imidazole salicylate The risk or severity of bleeding can be increased when Imidazole salicylate is combined with Omacetaxine mepesuccinate. Experimental Indobufen The risk or severity of bleeding can be increased when Indobufen is combined with Omacetaxine mepesuccinate. Investigational Indomethacin The risk or severity of bleeding can be increased when Indomethacin is combined with Omacetaxine mepesuccinate. Approved, Investigational Indoprofen The risk or severity of bleeding can be increased when Indoprofen is combined with Omacetaxine mepesuccinate. Withdrawn Isoxicam The risk or severity of bleeding can be increased when Isoxicam is combined with Omacetaxine mepesuccinate. Withdrawn Kebuzone The risk or severity of bleeding can be increased when Kebuzone is combined with Omacetaxine mepesuccinate. Experimental Ketoprofen The risk or severity of bleeding can be increased when Ketoprofen is combined with Omacetaxine mepesuccinate. Approved, Vet Approved Ketorolac The risk or severity of bleeding can be increased when Ketorolac is combined with Omacetaxine mepesuccinate. Approved Lanatoside C Lanatoside C may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Experimental Leflunomide The risk or severity of bleeding can be increased when Leflunomide is combined with Omacetaxine mepesuccinate. Approved, Investigational Lepirudin The risk or severity of bleeding can be increased when Lepirudin is combined with Omacetaxine mepesuccinate. Approved Letaxaban The risk or severity of bleeding can be increased when Letaxaban is combined with Omacetaxine mepesuccinate. Investigational Lisofylline The risk or severity of bleeding can be increased when Lisofylline is combined with Omacetaxine mepesuccinate. Investigational Lonazolac The risk or severity of bleeding can be increased when Lonazolac is combined with Omacetaxine mepesuccinate. Experimental Lornoxicam The risk or severity of bleeding can be increased when Lornoxicam is combined with Omacetaxine mepesuccinate. Approved, Investigational Loxoprofen The risk or severity of bleeding can be increased when Loxoprofen is combined with Omacetaxine mepesuccinate. Approved, Investigational Lumiracoxib The risk or severity of bleeding can be increased when Lumiracoxib is combined with Omacetaxine mepesuccinate. Approved, Investigational Magnesium salicylate The risk or severity of bleeding can be increased when Magnesium salicylate is combined with Omacetaxine mepesuccinate. Approved Masoprocol The risk or severity of bleeding can be increased when Masoprocol is combined with Omacetaxine mepesuccinate. Approved, Investigational Meclofenamic acid The risk or severity of bleeding can be increased when Meclofenamic acid is combined with Omacetaxine mepesuccinate. Approved, Vet Approved Mefenamic acid The risk or severity of bleeding can be increased when Mefenamic acid is combined with Omacetaxine mepesuccinate. Approved Melagatran The risk or severity of bleeding can be increased when Melagatran is combined with Omacetaxine mepesuccinate. Experimental Meloxicam The risk or severity of bleeding can be increased when Meloxicam is combined with Omacetaxine mepesuccinate. Approved, Vet Approved Mesalazine The risk or severity of bleeding can be increased when Mesalazine is combined with Omacetaxine mepesuccinate. Approved Metamizole The risk or severity of bleeding can be increased when Metamizole is combined with Omacetaxine mepesuccinate. Approved, Investigational, Withdrawn Metildigoxin Metildigoxin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Experimental Mizoribine The risk or severity of bleeding can be increased when Mizoribine is combined with Omacetaxine mepesuccinate. Investigational Mofebutazone The risk or severity of bleeding can be increased when Mofebutazone is combined with Omacetaxine mepesuccinate. Experimental Mycophenolate mofetil The risk or severity of bleeding can be increased when Mycophenolate mofetil is combined with Omacetaxine mepesuccinate. Approved, Investigational Mycophenolic acid The risk or severity of bleeding can be increased when Mycophenolic acid is combined with Omacetaxine mepesuccinate. Approved Nabumetone The risk or severity of bleeding can be increased when Nabumetone is combined with Omacetaxine mepesuccinate. Approved Nadroparin The risk or severity of bleeding can be increased when Nadroparin is combined with Omacetaxine mepesuccinate. Approved, Investigational Nafamostat The risk or severity of bleeding can be increased when Nafamostat is combined with Omacetaxine mepesuccinate. Approved, Investigational Naftifine The risk or severity of bleeding can be increased when Naftifine is combined with Omacetaxine mepesuccinate. Approved Naproxen The risk or severity of bleeding can be increased when Naproxen is combined with Omacetaxine mepesuccinate. Approved, Vet Approved Nepafenac The risk or severity of bleeding can be increased when Nepafenac is combined with Omacetaxine mepesuccinate. Approved, Investigational Nifenazone The risk or severity of bleeding can be increased when Nifenazone is combined with Omacetaxine mepesuccinate. Experimental Niflumic Acid The risk or severity of bleeding can be increased when Niflumic Acid is combined with Omacetaxine mepesuccinate. Approved Nimesulide The risk or severity of bleeding can be increased when Nimesulide is combined with Omacetaxine mepesuccinate. Approved, Investigational, Withdrawn Nitroaspirin The risk or severity of bleeding can be increased when Nitroaspirin is combined with Omacetaxine mepesuccinate. Investigational Oleandrin Oleandrin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Experimental, Investigational Olopatadine The risk or severity of bleeding can be increased when Olopatadine is combined with Omacetaxine mepesuccinate. Approved Olsalazine The risk or severity of bleeding can be increased when Olsalazine is combined with Omacetaxine mepesuccinate. Approved Orgotein The risk or severity of bleeding can be increased when Orgotein is combined with Omacetaxine mepesuccinate. Vet Approved Otamixaban The risk or severity of bleeding can be increased when Otamixaban is combined with Omacetaxine mepesuccinate. Investigational Ouabain Ouabain may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Approved Oxaprozin The risk or severity of bleeding can be increased when Oxaprozin is combined with Omacetaxine mepesuccinate. Approved Oxyphenbutazone The risk or severity of bleeding can be increased when Oxyphenbutazone is combined with Omacetaxine mepesuccinate. Approved, Withdrawn Paclitaxel The risk or severity of adverse effects can be increased when Paclitaxel is combined with Omacetaxine mepesuccinate. Approved, Vet Approved Parecoxib The risk or severity of bleeding can be increased when Parecoxib is combined with Omacetaxine mepesuccinate. Approved Parthenolide The risk or severity of bleeding can be increased when Parthenolide is combined with Omacetaxine mepesuccinate. Approved, Investigational Pentaerythritol Tetranitrate The risk or severity of bleeding can be increased when Pentaerythritol Tetranitrate is combined with Omacetaxine mepesuccinate. Approved Pentosan Polysulfate The risk or severity of bleeding can be increased when Pentosan Polysulfate is combined with Omacetaxine mepesuccinate. Approved Peruvoside Peruvoside may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Experimental Phenindione The risk or severity of bleeding can be increased when Phenindione is combined with Omacetaxine mepesuccinate. Approved, Investigational Phenprocoumon The risk or severity of bleeding can be increased when Phenprocoumon is combined with Omacetaxine mepesuccinate. Approved, Investigational Phenylbutazone The risk or severity of bleeding can be increased when Phenylbutazone is combined with Omacetaxine mepesuccinate. Approved, Vet Approved Pimecrolimus The risk or severity of bleeding can be increased when Pimecrolimus is combined with Omacetaxine mepesuccinate. Approved, Investigational Pirfenidone The risk or severity of bleeding can be increased when Pirfenidone is combined with Omacetaxine mepesuccinate. Approved, Investigational Piroxicam The risk or severity of bleeding can be increased when Piroxicam is combined with Omacetaxine mepesuccinate. Approved, Investigational Pirprofen The risk or severity of bleeding can be increased when Pirprofen is combined with Omacetaxine mepesuccinate. Experimental Pranoprofen The risk or severity of bleeding can be increased when Pranoprofen is combined with Omacetaxine mepesuccinate. Experimental, Investigational Proglumetacin The risk or severity of bleeding can be increased when Proglumetacin is combined with Omacetaxine mepesuccinate. Experimental Propacetamol The risk or severity of bleeding can be increased when Propacetamol is combined with Omacetaxine mepesuccinate. Approved, Investigational Propyphenazone The risk or severity of bleeding can be increased when Propyphenazone is combined with Omacetaxine mepesuccinate. Experimental Proquazone The risk or severity of bleeding can be increased when Proquazone is combined with Omacetaxine mepesuccinate. Experimental Proscillaridin Proscillaridin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate. Experimental Protein C The risk or severity of bleeding can be increased when Protein C is combined with Omacetaxine mepesuccinate. Approved Protein S human The risk or severity of bleeding can be increased when Protein S human is combined with Omacetaxine mepesuccinate. Approved Protocatechualdehyde The risk or severity of bleeding can be increased when Protocatechualdehyde is combined with Omacetaxine mepesuccinate. Approved PTC299 The risk or severity of bleeding can be increased when PTC299 is combined with Omacetaxine mepesuccinate. Investigational Resveratrol The risk or severity of bleeding can be increased when Resveratrol is combined with Omacetaxine mepesuccinate. Approved, Experimental, Investigational Reviparin The risk or severity of bleeding can be increased when Reviparin is combined with Omacetaxine mepesuccinate. Approved, Investigational Rivaroxaban The risk or severity of bleeding can be increased when Rivaroxaban is combined with Omacetaxine mepesuccinate. Approved Rofecoxib The risk or severity of bleeding can be increased when Rofecoxib is combined with Omacetaxine mepesuccinate. Approved, Investigational, Withdrawn Salicylamide The risk or severity of bleeding can be increased when Salicylamide is combined with Omacetaxine mepesuccinate. Approved Salicylic acid The risk or severity of bleeding can be increased when Salicylic acid is combined with Omacetaxine mepesuccinate. Approved, Investigational, Vet Approved Salsalate The risk or severity of bleeding can be increased when Salsalate is combined with Omacetaxine mepesuccinate. Approved Semapimod The risk or severity of bleeding can be increased when Semapimod is combined with Omacetaxine mepesuccinate. Investigational Seratrodast The risk or severity of bleeding can be increased when Seratrodast is combined with Omacetaxine mepesuccinate. Approved Serrapeptase The risk or severity of bleeding can be increased when Serrapeptase is combined with Omacetaxine mepesuccinate. Investigational SRT501 The risk or severity of bleeding can be increased when SRT501 is combined with Omacetaxine mepesuccinate. Investigational Sulfasalazine The risk or severity of bleeding can be increased when Sulfasalazine is combined with Omacetaxine mepesuccinate. Approved Sulindac The risk or severity of bleeding can be increased when Sulindac is combined with Omacetaxine mepesuccinate. Approved, Investigational Sulodexide The risk or severity of bleeding can be increased when Sulodexide is combined with Omacetaxine mepesuccinate. Approved, Investigational Suprofen The risk or severity of bleeding can be increased when Suprofen is combined with Omacetaxine mepesuccinate. Approved, Withdrawn Suxibuzone The risk or severity of bleeding can be increased when Suxibuzone is combined with Omacetaxine mepesuccinate. Experimental Tarenflurbil The risk or severity of bleeding can be increased when Tarenflurbil is combined with Omacetaxine mepesuccinate. Investigational Tenidap The risk or severity of bleeding can be increased when Tenidap is combined with Omacetaxine mepesuccinate. Experimental Tenoxicam The risk or severity of bleeding can be increased when Tenoxicam is combined with Omacetaxine mepesuccinate. Approved Tepoxalin The risk or severity of bleeding can be increased when Tepoxalin is combined with Omacetaxine mepesuccinate. Vet Approved Teriflunomide The risk or severity of bleeding can be increased when Teriflunomide is combined with Omacetaxine mepesuccinate. Approved Tiaprofenic acid The risk or severity of bleeding can be increased when Tiaprofenic acid is combined with Omacetaxine mepesuccinate. Approved Tinoridine The risk or severity of bleeding can be increased when Tinoridine is combined with Omacetaxine mepesuccinate. Investigational Tolfenamic Acid The risk or severity of bleeding can be increased when Tolfenamic Acid is combined with Omacetaxine mepesuccinate. Approved, Investigational Tolmetin The risk or severity of bleeding can be increased when Tolmetin is combined with Omacetaxine mepesuccinate. Approved Tranilast The risk or severity of bleeding can be increased when Tranilast is combined with Omacetaxine mepesuccinate. Approved, Investigational Trastuzumab Trastuzumab may increase the cardiotoxic activities of Omacetaxine mepesuccinate. Approved, Investigational Tribenoside The risk or severity of bleeding can be increased when Tribenoside is combined with Omacetaxine mepesuccinate. Experimental Triptolide The risk or severity of bleeding can be increased when Triptolide is combined with Omacetaxine mepesuccinate. Investigational Troxerutin The risk or severity of bleeding can be increased when Troxerutin is combined with Omacetaxine mepesuccinate. Investigational Valdecoxib The risk or severity of bleeding can be increased when Valdecoxib is combined with Omacetaxine mepesuccinate. Approved, Investigational, Withdrawn Warfarin The risk or severity of bleeding can be increased when Warfarin is combined with Omacetaxine mepesuccinate. Approved Ximelagatran The risk or severity of bleeding can be increased when Ximelagatran is combined with Omacetaxine mepesuccinate. Approved, Investigational, Withdrawn Zaltoprofen The risk or severity of bleeding can be increased when Zaltoprofen is combined with Omacetaxine mepesuccinate. Approved, Investigational Zileuton The risk or severity of bleeding can be increased when Zileuton is combined with Omacetaxine mepesuccinate. Approved, Investigational, Withdrawn Zomepirac The risk or severity of bleeding can be increased when Zomepirac is combined with Omacetaxine mepesuccinate. Withdrawn - Food Interactions
- Homoharringtonine is administered subcutaneously, so food should have no effects.
References
- Synthesis Reference
Yaguang Liu, "Process for producing harringtonine and homoharringtonine." U.S. Patent US4783454, issued June, 1980.
US4783454- General References
- Lou YJ, Qian WB, Jin J: Homoharringtonine induces apoptosis and growth arrest in human myeloma cells. Leuk Lymphoma. 2007 Jul;48(7):1400-6. [PubMed:17613769]
- Jie H, Donghua H, Xingkui X, Liang G, Wenjun W, Xiaoyan H, Zhen C: Homoharringtonine-induced apoptosis of MDS cell line MUTZ-1 cells is mediated by the endoplasmic reticulum stress pathway. Leuk Lymphoma. 2007 May;48(5):964-77. [PubMed:17487741]
- External Links
- KEGG Drug
- D08956
- PubChem Compound
- 285033
- PubChem Substance
- 175426874
- ChemSpider
- 251215
- ChEBI
- 71019
- ChEMBL
- CHEMBL46286
- HET
- HMT
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Omacetaxine_mepesuccinate
- ATC Codes
- L01XX40 — Omacetaxine mepesuccinate
- PDB Entries
- 3g6e / 6ek0
- FDA label
- Download (170 KB)
- MSDS
- Download (68.5 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Injection, powder, lyophilized, for solution Subcutaneous 3.5 mg/mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) USRE45128 No 1999-03-16 2019-03-16 US US6987103 No 2003-06-28 2023-06-28 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.108 mg/mL ALOGPS logP 2.09 ALOGPS logP 1.88 ChemAxon logS -3.7 ALOGPS pKa (Strongest Acidic) 12.09 ChemAxon pKa (Strongest Basic) 9.42 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 8 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 123.99 Å2 ChemAxon Rotatable Bond Count 11 ChemAxon Refractivity 142.07 m3·mol-1 ChemAxon Polarizability 57.62 Å3 ChemAxon Number of Rings 5 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.8077 Blood Brain Barrier - 0.5157 Caco-2 permeable - 0.5102 P-glycoprotein substrate Substrate 0.9056 P-glycoprotein inhibitor I Inhibitor 0.5183 P-glycoprotein inhibitor II Non-inhibitor 0.8527 Renal organic cation transporter Non-inhibitor 0.7406 CYP450 2C9 substrate Non-substrate 0.8857 CYP450 2D6 substrate Non-substrate 0.7052 CYP450 3A4 substrate Substrate 0.7613 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.923 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Inhibitor 0.796 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9428 Ames test Non AMES toxic 0.5243 Carcinogenicity Non-carcinogens 0.909 Biodegradation Not ready biodegradable 0.993 Rat acute toxicity 3.1592 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9292 hERG inhibition (predictor II) Non-inhibitor 0.8032
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-0002-0190070000-a017ab46c2f836fe8c26
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as cephalotaxus alkaloids. These are alkaloids with a structure based on the cephalotaxine skeleton, a tetracyclic 1,3-benzodioxole-containing compound which arises from the skeletal rearrangement of the hydroaromatic component of the Erythrina group.
- Kingdom
- Organic compounds
- Super Class
- Alkaloids and derivatives
- Class
- Cephalotaxus alkaloids
- Sub Class
- Not Available
- Direct Parent
- Cephalotaxus alkaloids
- Alternative Parents
- Benzazepines / Benzodioxoles / Aralkylamines / Azepines / Fatty acid methyl esters / Benzenoids / Dicarboxylic acids and derivatives / N-alkylpyrrolidines / Tertiary alcohols / Methyl esters show 9 more
- Substituents
- Cephalotaxine / Cephalotaxus alkaloid skeleton / Benzazepine / Benzodioxole / Fatty acid methyl ester / Azepine / Fatty acid ester / Aralkylamine / N-alkylpyrrolidine / Benzenoid show 25 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tertiary alcohol, organic heteropentacyclic compound, alkaloid ester, enol ether (CHEBI:71019)
Targets
- Kind
- Protein
- Organism
- Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Structural constituent of ribosome
- Specific Function
- One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have p...
- Gene Name
- rpl2
- Uniprot ID
- P20276
- Uniprot Name
- 50S ribosomal protein L2
- Molecular Weight
- 25308.485 Da
References
- Gurel G, Blaha G, Moore PB, Steitz TA: U2504 determines the species specificity of the A-site cleft antibiotics: the structures of tiamulin, homoharringtonine, and bruceantin bound to the ribosome. J Mol Biol. 2009 May 29;389(1):146-56. doi: 10.1016/j.jmb.2009.04.005. Epub 2009 Apr 9. [PubMed:19362093]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Structural constituent of ribosome
- Specific Function
- The L3 protein is a component of the large subunit of cytoplasmic ribosomes.
- Gene Name
- RPL3
- Uniprot ID
- P39023
- Uniprot Name
- 60S ribosomal protein L3
- Molecular Weight
- 46108.72 Da
References
- Tujebajeva RM, Graifer DM, Matasova NB, Fedorova OS, Odintsov VB, Ajtkhozhina NA, Karpova GG: Selective inhibition of the polypeptide chain elongation in eukaryotic cells. Biochim Biophys Acta. 1992 Jan 6;1129(2):177-82. [PubMed:1730056]
- Tujebajeva RM, Graifer DM, Karpova GG, Ajtkhozhina NA: Alkaloid homoharringtonine inhibits polypeptide chain elongation on human ribosomes on the step of peptide bond formation. FEBS Lett. 1989 Nov 6;257(2):254-6. [PubMed:2583270]
Drug created on October 19, 2007 17:15 / Updated on March 02, 2018 05:26