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Identification
NameOmacetaxine mepesuccinate
Accession NumberDB04865
TypeSmall Molecule
GroupsApproved
DescriptionOmacetaxine 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
Thumb
Synonyms
(−)-homoharringtonine
(2'R,3S,4S,5R)-(−)-homoharringtonine
HHT
Homoharringtonin
Homoharringtonine
External Identifiers
  • CGX-635
  • NSC-141633
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SynriboInjection, powder, lyophilized, for solution3.5 mg/mLSubcutaneousCephalon, Inc.2012-11-19Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CeflatoninChemGenex Therapeutics
MyelostatNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Omacetaxine mepesuccinate hydrochloride
457895-79-3
Thumb
  • InChI Key: RRNSZQVHVKGKOS-CALFFDBBSA-N
  • Monoisotopic Mass: 581.2391596
  • Average Mass: 582.09
DBSALT001930
Categories
UNII6FG8041S5B
CAS number26833-87-4
WeightAverage: 545.6213
Monoisotopic: 545.262481851
Chemical FormulaC29H39NO9
InChI KeyHYFHYPWGAURHIV-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][C@@]1(OC(=O)[C@@](O)(CCCC(C)(C)O)CC(=O)OC)C(OC)=C[C@]23CCCN2CCC2=CC4=C(OCO4)C=C2[C@]13[H]
Pharmacology
IndicationUsed 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
PharmacodynamicsThe 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 actionHomoharringtonine 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
50S ribosomal protein L2Proteinyes
antagonist
Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)P20276 details
60S ribosomal protein L3Proteinyes
antagonist
HumanP39023 details
Related Articles
AbsorptionHomoharringtonine 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 bindingPlasma 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 eliminationThe main route of elimination for homoharringtonine is still unknown, but renal elimination is less than 15%.
Half lifeHomoharringtonine has a half life of about 6 hours after subcutaneous administration.
Clearance

Clearance for homoharringtonine was not quantified.

ToxicityThe most severe adverse effects after homoharringtonine administration are myelosuppression, bleeding, hyperglycemia, and fetal harm.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Omacetaxine mepesuccinate.Approved
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with Omacetaxine mepesuccinate.Approved
AcenocoumarolThe risk or severity of adverse effects can be increased when Acenocoumarol is combined with Omacetaxine mepesuccinate.Approved
AcetovanilloneThe risk or severity of adverse effects can be increased when Acetovanillone is combined with Omacetaxine mepesuccinate.Investigational
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate.Approved
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
AdapaleneThe risk or severity of adverse effects can be increased when Adapalene is combined with Omacetaxine mepesuccinate.Approved
AncrodThe risk or severity of adverse effects can be increased when Ancrod is combined with Omacetaxine mepesuccinate.Investigational
AnisodamineThe risk or severity of adverse effects can be increased when Anisodamine is combined with Omacetaxine mepesuccinate.Investigational
AntipyrineThe risk or severity of adverse effects can be increased when Antipyrine is combined with Omacetaxine mepesuccinate.Approved
Antithrombin III humanThe risk or severity of adverse effects can be increased when Antithrombin III human is combined with Omacetaxine mepesuccinate.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Omacetaxine mepesuccinate.Investigational
ApixabanThe risk or severity of adverse effects can be increased when Apixaban is combined with Omacetaxine mepesuccinate.Approved
ApremilastThe risk or severity of adverse effects can be increased when Apremilast is combined with Omacetaxine mepesuccinate.Approved, Investigational
ArdeparinThe risk or severity of adverse effects can be increased when Ardeparin is combined with Omacetaxine mepesuccinate.Approved, Withdrawn
ArgatrobanThe risk or severity of adverse effects can be increased when Argatroban is combined with Omacetaxine mepesuccinate.Approved, Investigational
AzapropazoneThe risk or severity of adverse effects can be increased when Azapropazone is combined with Omacetaxine mepesuccinate.Withdrawn
AzelastineThe risk or severity of adverse effects can be increased when Azelastine is combined with Omacetaxine mepesuccinate.Approved
BalsalazideThe risk or severity of adverse effects can be increased when Balsalazide is combined with Omacetaxine mepesuccinate.Approved, Investigational
BecaplerminThe risk or severity of adverse effects can be increased when Becaplermin is combined with Omacetaxine mepesuccinate.Approved, Investigational
BenoxaprofenThe risk or severity of adverse effects can be increased when Benoxaprofen is combined with Omacetaxine mepesuccinate.Withdrawn
Betulinic AcidThe risk or severity of adverse effects can be increased when Betulinic Acid is combined with Omacetaxine mepesuccinate.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Omacetaxine mepesuccinate.Approved, Investigational
BivalirudinThe risk or severity of adverse effects can be increased when Bivalirudin is combined with Omacetaxine mepesuccinate.Approved, Investigational
BromfenacThe risk or severity of adverse effects can be increased when Bromfenac is combined with Omacetaxine mepesuccinate.Approved
BucillamineThe risk or severity of adverse effects can be increased when Bucillamine is combined with Omacetaxine mepesuccinate.Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Omacetaxine mepesuccinate.Approved
CarprofenThe risk or severity of adverse effects can be increased when Carprofen is combined with Omacetaxine mepesuccinate.Approved, Vet Approved, Withdrawn
CastanospermineThe risk or severity of adverse effects can be increased when Castanospermine is combined with Omacetaxine mepesuccinate.Experimental
CelecoxibThe risk or severity of adverse effects can be increased when Celecoxib is combined with Omacetaxine mepesuccinate.Approved, Investigational
CertoparinThe risk or severity of adverse effects can be increased when Certoparin is combined with Omacetaxine mepesuccinate.Approved
ChloroquineThe risk or severity of adverse effects can be increased when Chloroquine is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
Citric AcidThe risk or severity of adverse effects can be increased when Citric Acid is combined with Omacetaxine mepesuccinate.Nutraceutical, Vet Approved
ClonixinThe risk or severity of adverse effects can be increased when Clonixin is combined with Omacetaxine mepesuccinate.Approved
CurcuminThe risk or severity of adverse effects can be increased when Curcumin is combined with Omacetaxine mepesuccinate.Investigational
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Omacetaxine mepesuccinate.Approved, Investigational
D-LimoneneThe risk or severity of adverse effects can be increased when D-Limonene is combined with Omacetaxine mepesuccinate.Investigational
Dabigatran etexilateThe risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Omacetaxine mepesuccinate.Approved
DalteparinThe risk or severity of adverse effects can be increased when Dalteparin is combined with Omacetaxine mepesuccinate.Approved
DanaparoidThe risk or severity of adverse effects can be increased when Danaparoid is combined with Omacetaxine mepesuccinate.Approved, Withdrawn
DesirudinThe risk or severity of adverse effects can be increased when Desirudin is combined with Omacetaxine mepesuccinate.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Omacetaxine mepesuccinate.Approved
DextranThe risk or severity of adverse effects can be increased when Dextran is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
Dextran 40The risk or severity of adverse effects can be increased when Dextran 40 is combined with Omacetaxine mepesuccinate.Approved
Dextran 70The risk or severity of adverse effects can be increased when Dextran 70 is combined with Omacetaxine mepesuccinate.Approved
Dextran 75The risk or severity of adverse effects can be increased when Dextran 75 is combined with Omacetaxine mepesuccinate.Approved
DiclofenacThe risk or severity of adverse effects can be increased when Diclofenac is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
DicoumarolThe risk or severity of adverse effects can be increased when Dicoumarol is combined with Omacetaxine mepesuccinate.Approved
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Omacetaxine mepesuccinate.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Omacetaxine mepesuccinate.Approved, Investigational
DroxicamThe risk or severity of adverse effects can be increased when Droxicam is combined with Omacetaxine mepesuccinate.Approved
DuvelisibThe risk or severity of adverse effects can be increased when Duvelisib is combined with Omacetaxine mepesuccinate.Investigational
E6201The risk or severity of adverse effects can be increased when E6201 is combined with Omacetaxine mepesuccinate.Investigational
EbselenThe risk or severity of adverse effects can be increased when Ebselen is combined with Omacetaxine mepesuccinate.Investigational
Edetic AcidThe risk or severity of adverse effects can be increased when Edetic Acid is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
EdoxabanThe risk or severity of adverse effects can be increased when Edoxaban is combined with Omacetaxine mepesuccinate.Approved
EnoxaparinThe risk or severity of adverse effects can be increased when Enoxaparin is combined with Omacetaxine mepesuccinate.Approved
EpirizoleThe risk or severity of adverse effects can be increased when Epirizole is combined with Omacetaxine mepesuccinate.Approved
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Omacetaxine mepesuccinate.Approved, Investigational
Ethyl biscoumacetateThe risk or severity of adverse effects can be increased when Ethyl biscoumacetate is combined with Omacetaxine mepesuccinate.Withdrawn
EtodolacThe risk or severity of adverse effects can be increased when Etodolac is combined with Omacetaxine mepesuccinate.Approved, Investigational, Vet Approved
EtofenamateThe risk or severity of adverse effects can be increased when Etofenamate is combined with Omacetaxine mepesuccinate.Approved
EtoricoxibThe risk or severity of adverse effects can be increased when Etoricoxib is combined with Omacetaxine mepesuccinate.Approved, Investigational
Evening primrose oilThe risk or severity of adverse effects can be increased when Evening primrose oil is combined with Omacetaxine mepesuccinate.Approved
exisulindThe risk or severity of adverse effects can be increased when exisulind is combined with Omacetaxine mepesuccinate.Investigational
FenbufenThe risk or severity of adverse effects can be increased when Fenbufen is combined with Omacetaxine mepesuccinate.Approved
FenoprofenThe risk or severity of adverse effects can be increased when Fenoprofen is combined with Omacetaxine mepesuccinate.Approved
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Omacetaxine mepesuccinate.Approved, Withdrawn
FluindioneThe risk or severity of adverse effects can be increased when Fluindione is combined with Omacetaxine mepesuccinate.Investigational
FlunixinThe risk or severity of adverse effects can be increased when Flunixin is combined with Omacetaxine mepesuccinate.Vet Approved
FlurbiprofenThe risk or severity of adverse effects can be increased when Flurbiprofen is combined with Omacetaxine mepesuccinate.Approved, Investigational
FondaparinuxThe risk or severity of adverse effects can be increased when Fondaparinux is combined with Omacetaxine mepesuccinate.Investigational
Fondaparinux sodiumThe risk or severity of adverse effects can be increased when Fondaparinux sodium is combined with Omacetaxine mepesuccinate.Approved, Investigational
GabexateThe risk or severity of adverse effects can be increased when Gabexate is combined with Omacetaxine mepesuccinate.Investigational
HeparinThe risk or severity of adverse effects can be increased when Heparin is combined with Omacetaxine mepesuccinate.Approved, Investigational
HigenamineThe risk or severity of adverse effects can be increased when Higenamine is combined with Omacetaxine mepesuccinate.Investigational
HirulogThe risk or severity of adverse effects can be increased when Hirulog is combined with Omacetaxine mepesuccinate.Experimental
HMPL-004The risk or severity of adverse effects can be increased when HMPL-004 is combined with Omacetaxine mepesuccinate.Investigational
IbuprofenThe risk or severity of adverse effects can be increased when Ibuprofen is combined with Omacetaxine mepesuccinate.Approved
IbuproxamThe risk or severity of adverse effects can be increased when Ibuproxam is combined with Omacetaxine mepesuccinate.Withdrawn
IcatibantThe risk or severity of adverse effects can be increased when Icatibant is combined with Omacetaxine mepesuccinate.Approved
idraparinuxThe risk or severity of adverse effects can be increased when idraparinux is combined with Omacetaxine mepesuccinate.Investigational
IndomethacinThe risk or severity of adverse effects can be increased when Indomethacin is combined with Omacetaxine mepesuccinate.Approved, Investigational
IndoprofenThe risk or severity of adverse effects can be increased when Indoprofen is combined with Omacetaxine mepesuccinate.Withdrawn
IsoxicamThe risk or severity of adverse effects can be increased when Isoxicam is combined with Omacetaxine mepesuccinate.Withdrawn
KebuzoneThe risk or severity of adverse effects can be increased when Kebuzone is combined with Omacetaxine mepesuccinate.Experimental
KetoprofenThe risk or severity of adverse effects can be increased when Ketoprofen is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
KetorolacThe risk or severity of adverse effects can be increased when Ketorolac is combined with Omacetaxine mepesuccinate.Approved
LeflunomideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Omacetaxine mepesuccinate.Approved, Investigational
LepirudinThe risk or severity of adverse effects can be increased when Lepirudin is combined with Omacetaxine mepesuccinate.Approved
LisofyllineThe risk or severity of adverse effects can be increased when Lisofylline is combined with Omacetaxine mepesuccinate.Investigational
LornoxicamThe risk or severity of adverse effects can be increased when Lornoxicam is combined with Omacetaxine mepesuccinate.Approved
LoxoprofenThe risk or severity of adverse effects can be increased when Loxoprofen is combined with Omacetaxine mepesuccinate.Approved
LumiracoxibThe risk or severity of adverse effects can be increased when Lumiracoxib is combined with Omacetaxine mepesuccinate.Approved, Investigational
Magnesium salicylateThe risk or severity of adverse effects can be increased when Magnesium salicylate is combined with Omacetaxine mepesuccinate.Approved
MasoprocolThe risk or severity of adverse effects can be increased when Masoprocol is combined with Omacetaxine mepesuccinate.Approved
Meclofenamic acidThe risk or severity of adverse effects can be increased when Meclofenamic acid is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
Mefenamic acidThe risk or severity of adverse effects can be increased when Mefenamic acid is combined with Omacetaxine mepesuccinate.Approved
MeloxicamThe risk or severity of adverse effects can be increased when Meloxicam is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
MesalazineThe risk or severity of adverse effects can be increased when Mesalazine is combined with Omacetaxine mepesuccinate.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Omacetaxine mepesuccinate.Withdrawn
MizoribineThe risk or severity of adverse effects can be increased when Mizoribine is combined with Omacetaxine mepesuccinate.Investigational
Mycophenolate mofetilThe risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Omacetaxine mepesuccinate.Approved, Investigational
Mycophenolic acidThe risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Omacetaxine mepesuccinate.Approved
NabumetoneThe risk or severity of adverse effects can be increased when Nabumetone is combined with Omacetaxine mepesuccinate.Approved
NadroparinThe risk or severity of adverse effects can be increased when Nadroparin is combined with Omacetaxine mepesuccinate.Approved
NafamostatThe risk or severity of adverse effects can be increased when Nafamostat is combined with Omacetaxine mepesuccinate.Investigational
NaftifineThe risk or severity of adverse effects can be increased when Naftifine is combined with Omacetaxine mepesuccinate.Approved
NaproxenThe risk or severity of adverse effects can be increased when Naproxen is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
NCX 4016The risk or severity of adverse effects can be increased when NCX 4016 is combined with Omacetaxine mepesuccinate.Investigational
NepafenacThe risk or severity of adverse effects can be increased when Nepafenac is combined with Omacetaxine mepesuccinate.Approved
Niflumic AcidThe risk or severity of adverse effects can be increased when Niflumic Acid is combined with Omacetaxine mepesuccinate.Approved
NimesulideThe risk or severity of adverse effects can be increased when Nimesulide is combined with Omacetaxine mepesuccinate.Approved, Withdrawn
NitroaspirinThe risk or severity of adverse effects can be increased when Nitroaspirin is combined with Omacetaxine mepesuccinate.Investigational
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Omacetaxine mepesuccinate.Approved
OlsalazineThe risk or severity of adverse effects can be increased when Olsalazine is combined with Omacetaxine mepesuccinate.Approved
OrgoteinThe risk or severity of adverse effects can be increased when Orgotein is combined with Omacetaxine mepesuccinate.Vet Approved
OtamixabanThe risk or severity of adverse effects can be increased when Otamixaban is combined with Omacetaxine mepesuccinate.Investigational
OuabainOuabain may decrease the cardiotoxic activities of Omacetaxine mepesuccinate.Approved
OxaprozinThe risk or severity of adverse effects can be increased when Oxaprozin is combined with Omacetaxine mepesuccinate.Approved
OxyphenbutazoneThe risk or severity of adverse effects can be increased when Oxyphenbutazone is combined with Omacetaxine mepesuccinate.Withdrawn
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
ParecoxibThe risk or severity of adverse effects can be increased when Parecoxib is combined with Omacetaxine mepesuccinate.Approved
Pentosan PolysulfateThe risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Omacetaxine mepesuccinate.Approved
PhenindioneThe risk or severity of adverse effects can be increased when Phenindione is combined with Omacetaxine mepesuccinate.Approved
PhenprocoumonThe risk or severity of adverse effects can be increased when Phenprocoumon is combined with Omacetaxine mepesuccinate.Approved
PhenylbutazoneThe risk or severity of adverse effects can be increased when Phenylbutazone is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Omacetaxine mepesuccinate.Approved, Investigational
PirfenidoneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Omacetaxine mepesuccinate.Investigational
PiroxicamThe risk or severity of adverse effects can be increased when Piroxicam is combined with Omacetaxine mepesuccinate.Approved, Investigational
PropacetamolThe risk or severity of adverse effects can be increased when Propacetamol is combined with Omacetaxine mepesuccinate.Approved
Protein CThe risk or severity of adverse effects can be increased when Protein C is combined with Omacetaxine mepesuccinate.Approved
Protein S humanThe risk or severity of adverse effects can be increased when Protein S human is combined with Omacetaxine mepesuccinate.Approved
ProtocatechualdehydeThe risk or severity of adverse effects can be increased when Protocatechualdehyde is combined with Omacetaxine mepesuccinate.Approved
PTC299The risk or severity of adverse effects can be increased when PTC299 is combined with Omacetaxine mepesuccinate.Investigational
ResveratrolThe risk or severity of adverse effects can be increased when Resveratrol is combined with Omacetaxine mepesuccinate.Experimental, Investigational
ReviparinThe risk or severity of adverse effects can be increased when Reviparin is combined with Omacetaxine mepesuccinate.Approved
RivaroxabanThe risk or severity of adverse effects can be increased when Rivaroxaban is combined with Omacetaxine mepesuccinate.Approved
RofecoxibThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Omacetaxine mepesuccinate.Investigational, Withdrawn
SalicylamideThe risk or severity of adverse effects can be increased when Salicylamide is combined with Omacetaxine mepesuccinate.Approved
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Omacetaxine mepesuccinate.Approved, Vet Approved
SalsalateThe risk or severity of adverse effects can be increased when Salsalate is combined with Omacetaxine mepesuccinate.Approved
SeratrodastThe risk or severity of adverse effects can be increased when Seratrodast is combined with Omacetaxine mepesuccinate.Approved, Investigational
SRT501The risk or severity of adverse effects can be increased when SRT501 is combined with Omacetaxine mepesuccinate.Investigational
SulfasalazineThe risk or severity of adverse effects can be increased when Sulfasalazine is combined with Omacetaxine mepesuccinate.Approved
SulindacThe risk or severity of adverse effects can be increased when Sulindac is combined with Omacetaxine mepesuccinate.Approved
SulodexideThe risk or severity of adverse effects can be increased when Sulodexide is combined with Omacetaxine mepesuccinate.Approved, Investigational
SuprofenThe risk or severity of adverse effects can be increased when Suprofen is combined with Omacetaxine mepesuccinate.Approved, Withdrawn
TenoxicamThe risk or severity of adverse effects can be increased when Tenoxicam is combined with Omacetaxine mepesuccinate.Approved
TepoxalinThe risk or severity of adverse effects can be increased when Tepoxalin is combined with Omacetaxine mepesuccinate.Vet Approved
TeriflunomideThe risk or severity of adverse effects can be increased when Teriflunomide is combined with Omacetaxine mepesuccinate.Approved
Tiaprofenic acidThe risk or severity of adverse effects can be increased when Tiaprofenic acid is combined with Omacetaxine mepesuccinate.Approved
TinoridineThe risk or severity of adverse effects can be increased when Tinoridine is combined with Omacetaxine mepesuccinate.Investigational
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Tolfenamic Acid is combined with Omacetaxine mepesuccinate.Approved
TolmetinThe risk or severity of adverse effects can be increased when Tolmetin is combined with Omacetaxine mepesuccinate.Approved
TranilastThe risk or severity of adverse effects can be increased when Tranilast is combined with Omacetaxine mepesuccinate.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Omacetaxine mepesuccinate.Approved, Investigational
Trisalicylate-cholineThe risk or severity of adverse effects can be increased when Trisalicylate-choline is combined with Omacetaxine mepesuccinate.Approved
ValdecoxibThe risk or severity of adverse effects can be increased when Valdecoxib is combined with Omacetaxine mepesuccinate.Investigational, Withdrawn
WarfarinThe risk or severity of adverse effects can be increased when Warfarin is combined with Omacetaxine mepesuccinate.Approved
XimelagatranThe risk or severity of adverse effects can be increased when Ximelagatran is combined with Omacetaxine mepesuccinate.Approved, Investigational, Withdrawn
Ym150The risk or severity of adverse effects can be increased when Ym150 is combined with Omacetaxine mepesuccinate.Investigational
ZaltoprofenThe risk or severity of adverse effects can be increased when Zaltoprofen is combined with Omacetaxine mepesuccinate.Approved
ZileutonThe risk or severity of adverse effects can be increased when Zileuton is combined with Omacetaxine mepesuccinate.Approved, Investigational, Withdrawn
ZomepiracThe risk or severity of adverse effects 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
  1. 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 ]
  2. 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
ATC CodesL01XX40
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (170 KB)
MSDSDownload (68.5 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8077
Blood Brain Barrier-0.5157
Caco-2 permeable-0.5102
P-glycoprotein substrateSubstrate0.9056
P-glycoprotein inhibitor IInhibitor0.5183
P-glycoprotein inhibitor IINon-inhibitor0.8527
Renal organic cation transporterNon-inhibitor0.7406
CYP450 2C9 substrateNon-substrate0.8857
CYP450 2D6 substrateNon-substrate0.7052
CYP450 3A4 substrateSubstrate0.7613
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9428
Ames testNon AMES toxic0.5243
CarcinogenicityNon-carcinogens0.909
BiodegradationNot ready biodegradable0.993
Rat acute toxicity3.1592 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9292
hERG inhibition (predictor II)Non-inhibitor0.8032
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionSubcutaneous3.5 mg/mL
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6987103 No2003-06-282023-06-28Us
USRE45128 No1999-03-162019-03-16Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.108 mg/mLALOGPS
logP2.09ALOGPS
logP1.88ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)12.09ChemAxon
pKa (Strongest Basic)9.42ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area123.99 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity142.07 m3·mol-1ChemAxon
Polarizability57.62 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassCephalotaxus alkaloids
Sub ClassNot Available
Direct ParentCephalotaxus alkaloids
Alternative Parents
Substituents
  • Cephalotaxine
  • Cephalotaxus alkaloid skeleton
  • Benzazepine
  • Benzodioxole
  • Aralkylamine
  • Fatty acid methyl ester
  • Fatty acid ester
  • Beta-hydroxy acid
  • Azepine
  • Fatty acyl
  • Benzenoid
  • N-alkylpyrrolidine
  • Hydroxy acid
  • Dicarboxylic acid or derivatives
  • Methyl ester
  • Tertiary alcohol
  • Pyrrolidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Acetal
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

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 peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome (By similarity).
Gene Name:
rpl2
Uniprot ID:
P20276
Molecular Weight:
25308.485 Da
References
  1. 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
Molecular Weight:
46108.72 Da
References
  1. 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 ]
  2. 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 ]
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Drug created on October 19, 2007 17:15 / Updated on December 02, 2016 02:44