Omacetaxine mepesuccinate

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (2)

Identification

Name

Omacetaxine mepesuccinate

Accession Number

DB04865

Type

Small Molecule

Groups

Approved

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

MOL SDF 3D-SDF PDB SMILES InChI View 3D 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	Details
Omacetaxine mepesuccinate hydrochloride	563OX5661H	457895-79-3	RRNSZQVHVKGKOS-CALFFDBBSA-N	Details

Approved 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

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Ceflatonin	ChemGenex Therapeutics
Myelostat	Not Available

Brand mixtures

Not Available

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][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

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	Kind	Pharmacological action	Actions	Organism	UniProt ID
50S ribosomal protein L2	Protein	yes	antagonist	Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809)	P20276	details
60S ribosomal protein L3	Protein	yes	antagonist	Human	P39023	details

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
Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Omacetaxine mepesuccinate.	Approved
Aceclofenac	The risk or severity of adverse effects can be increased when Aceclofenac is combined with Omacetaxine mepesuccinate.	Approved
Acenocoumarol	The risk or severity of adverse effects can be increased when Acenocoumarol is combined with Omacetaxine mepesuccinate.	Approved
Acetyldigitoxin	Acetyldigitoxin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate.	Approved
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 adverse effects can be increased when Adapalene is combined with Omacetaxine mepesuccinate.	Approved
Ancrod	The risk or severity of adverse effects can be increased when Ancrod is combined with Omacetaxine mepesuccinate.	Investigational
Andrographolide	The risk or severity of adverse effects can be increased when HMPL-004 is combined with Omacetaxine mepesuccinate.	Investigational
Anisodamine	The risk or severity of adverse effects can be increased when Anisodamine is combined with Omacetaxine mepesuccinate.	Investigational
Antipyrine	The risk or severity of adverse effects can be increased when Antipyrine is combined with Omacetaxine mepesuccinate.	Approved
Antithrombin III human	The risk or severity of adverse effects can be increased when Antithrombin III human is combined with Omacetaxine mepesuccinate.	Approved
Apixaban	The risk or severity of adverse effects can be increased when Apixaban is combined with Omacetaxine mepesuccinate.	Approved
Apocynin	The risk or severity of adverse effects can be increased when Acetovanillone is combined with Omacetaxine mepesuccinate.	Investigational
Apremilast	The risk or severity of adverse effects can be increased when Apremilast is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Ardeparin	The risk or severity of adverse effects can be increased when Ardeparin is combined with Omacetaxine mepesuccinate.	Approved, Withdrawn
Argatroban	The risk or severity of adverse effects can be increased when Argatroban is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Azapropazone	The risk or severity of adverse effects can be increased when Azapropazone is combined with Omacetaxine mepesuccinate.	Withdrawn
Azelastine	The risk or severity of adverse effects can be increased when Azelastine is combined with Omacetaxine mepesuccinate.	Approved
Balsalazide	The risk or severity of adverse effects can be increased when Balsalazide is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Becaplermin	The risk or severity of adverse effects can be increased when Becaplermin is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Benoxaprofen	The risk or severity of adverse effects can be increased when Benoxaprofen is combined with Omacetaxine mepesuccinate.	Withdrawn
Betulinic Acid	The risk or severity of adverse effects can be increased when Betulinic Acid is combined with Omacetaxine mepesuccinate.	Investigational
Bevacizumab	Bevacizumab may increase the cardiotoxic activities of Omacetaxine mepesuccinate.	Approved, Investigational
Bivalirudin	The risk or severity of adverse effects can be increased when Bivalirudin is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Bromfenac	The risk or severity of adverse effects can be increased when Bromfenac is combined with Omacetaxine mepesuccinate.	Approved
Bucillamine	The risk or severity of adverse effects can be increased when Bucillamine is combined with Omacetaxine mepesuccinate.	Investigational
Cabazitaxel	The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Omacetaxine mepesuccinate.	Approved
Carprofen	The risk or severity of adverse effects can be increased when Carprofen is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved, Withdrawn
Castanospermine	The risk or severity of adverse effects can be increased when Castanospermine is combined with Omacetaxine mepesuccinate.	Experimental
Celecoxib	The risk or severity of adverse effects can be increased when Celecoxib is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Certoparin	The risk or severity of adverse effects can be increased when Certoparin is combined with Omacetaxine mepesuccinate.	Approved
Chloroquine	The risk or severity of adverse effects can be increased when Chloroquine is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved
Choline magnesium trisalicylate	The risk or severity of adverse effects can be increased when Trisalicylate-choline is combined with Omacetaxine mepesuccinate.	Approved
Citric Acid	The risk or severity of adverse effects can be increased when Citric Acid is combined with Omacetaxine mepesuccinate.	Nutraceutical, Vet Approved
Clonixin	The risk or severity of adverse effects can be increased when Clonixin is combined with Omacetaxine mepesuccinate.	Approved
Curcumin	The risk or severity of adverse effects can be increased when Curcumin is combined with Omacetaxine mepesuccinate.	Investigational
Cyclophosphamide	Cyclophosphamide may increase the cardiotoxic activities of Omacetaxine mepesuccinate.	Approved, Investigational
Dabigatran etexilate	The risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Omacetaxine mepesuccinate.	Approved
Dalteparin	The risk or severity of adverse effects can be increased when Dalteparin is combined with Omacetaxine mepesuccinate.	Approved
Darexaban	The risk or severity of adverse effects can be increased when Ym150 is combined with Omacetaxine mepesuccinate.	Investigational
Desirudin	The risk or severity of adverse effects 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 adverse effects can be increased when Dextran is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved
Dextran 40	The risk or severity of adverse effects can be increased when Dextran 40 is combined with Omacetaxine mepesuccinate.	Approved
Diclofenac	The risk or severity of adverse effects can be increased when Diclofenac is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved
Dicoumarol	The risk or severity of adverse effects can be increased when Dicoumarol is combined with Omacetaxine mepesuccinate.	Approved
Diflunisal	The risk or severity of adverse effects can be increased when Diflunisal is combined with Omacetaxine mepesuccinate.	Approved
Digitoxin	Digitoxin may decrease the cardiotoxic activities of Omacetaxine mepesuccinate.	Approved
Digoxin	Digoxin 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 adverse effects can be increased when Droxicam is combined with Omacetaxine mepesuccinate.	Approved
Duvelisib	The risk or severity of adverse effects can be increased when Duvelisib is combined with Omacetaxine mepesuccinate.	Investigational
E-6201	The risk or severity of adverse effects can be increased when E6201 is combined with Omacetaxine mepesuccinate.	Investigational
Ebselen	The risk or severity of adverse effects can be increased when Ebselen is combined with Omacetaxine mepesuccinate.	Investigational
Edetic Acid	The risk or severity of adverse effects can be increased when Edetic Acid is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved
Edoxaban	The risk or severity of adverse effects can be increased when Edoxaban is combined with Omacetaxine mepesuccinate.	Approved
Enoxaparin	The risk or severity of adverse effects can be increased when Enoxaparin is combined with Omacetaxine mepesuccinate.	Approved
Epirizole	The risk or severity of adverse effects can be increased when Epirizole is combined with Omacetaxine mepesuccinate.	Approved
Etanercept	The risk or severity of adverse effects can be increased when Etanercept is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Ethyl biscoumacetate	The risk or severity of adverse effects can be increased when Ethyl biscoumacetate is combined with Omacetaxine mepesuccinate.	Withdrawn
Etodolac	The risk or severity of adverse effects can be increased when Etodolac is combined with Omacetaxine mepesuccinate.	Approved, Investigational, Vet Approved
Etofenamate	The risk or severity of adverse effects can be increased when Etofenamate is combined with Omacetaxine mepesuccinate.	Approved
Etoricoxib	The risk or severity of adverse effects can be increased when Etoricoxib is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Fenbufen	The risk or severity of adverse effects can be increased when Fenbufen is combined with Omacetaxine mepesuccinate.	Approved
Fenoprofen	The risk or severity of adverse effects can be increased when Fenoprofen is combined with Omacetaxine mepesuccinate.	Approved
Floctafenine	The risk or severity of adverse effects can be increased when Floctafenine is combined with Omacetaxine mepesuccinate.	Approved, Withdrawn
Fluindione	The risk or severity of adverse effects can be increased when Fluindione is combined with Omacetaxine mepesuccinate.	Investigational
Flurbiprofen	The risk or severity of adverse effects can be increased when Flurbiprofen is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Fondaparinux	The risk or severity of adverse effects can be increased when Fondaparinux is combined with Omacetaxine mepesuccinate.	Investigational
Fondaparinux sodium	The risk or severity of adverse effects can be increased when Fondaparinux sodium is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Gabexate	The risk or severity of adverse effects can be increased when Gabexate is combined with Omacetaxine mepesuccinate.	Investigational
Heparin	The risk or severity of adverse effects can be increased when Heparin is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Higenamine	The risk or severity of adverse effects can be increased when Higenamine is combined with Omacetaxine mepesuccinate.	Investigational
Ibuprofen	The risk or severity of adverse effects can be increased when Ibuprofen is combined with Omacetaxine mepesuccinate.	Approved
Ibuproxam	The risk or severity of adverse effects can be increased when Ibuproxam is combined with Omacetaxine mepesuccinate.	Withdrawn
Icatibant	The risk or severity of adverse effects can be increased when Icatibant is combined with Omacetaxine mepesuccinate.	Approved
Indomethacin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Indoprofen	The risk or severity of adverse effects can be increased when Indoprofen is combined with Omacetaxine mepesuccinate.	Withdrawn
Isoxicam	The risk or severity of adverse effects can be increased when Isoxicam is combined with Omacetaxine mepesuccinate.	Withdrawn
Kebuzone	The risk or severity of adverse effects can be increased when Kebuzone is combined with Omacetaxine mepesuccinate.	Experimental
Ketoprofen	The risk or severity of adverse effects can be increased when Ketoprofen is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved
Ketorolac	The risk or severity of adverse effects can be increased when Ketorolac is combined with Omacetaxine mepesuccinate.	Approved
Leflunomide	The risk or severity of adverse effects can be increased when Leflunomide is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Lepirudin	The risk or severity of adverse effects can be increased when Lepirudin is combined with Omacetaxine mepesuccinate.	Approved
Lisofylline	The risk or severity of adverse effects can be increased when Lisofylline is combined with Omacetaxine mepesuccinate.	Investigational
Lornoxicam	The risk or severity of adverse effects can be increased when Lornoxicam is combined with Omacetaxine mepesuccinate.	Approved
Loxoprofen	The risk or severity of adverse effects can be increased when Loxoprofen is combined with Omacetaxine mepesuccinate.	Approved
Lumiracoxib	The risk or severity of adverse effects can be increased when Lumiracoxib is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Magnesium salicylate	The risk or severity of adverse effects can be increased when Magnesium salicylate is combined with Omacetaxine mepesuccinate.	Approved
Masoprocol	The risk or severity of adverse effects can be increased when Masoprocol is combined with Omacetaxine mepesuccinate.	Approved
Meclofenamic acid	The risk or severity of adverse effects can be increased when Meclofenamic acid is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved
Mefenamic acid	The risk or severity of adverse effects can be increased when Mefenamic acid is combined with Omacetaxine mepesuccinate.	Approved
Meloxicam	The risk or severity of adverse effects can be increased when Meloxicam is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved
Mesalazine	The risk or severity of adverse effects can be increased when Mesalazine is combined with Omacetaxine mepesuccinate.	Approved
Metamizole	The risk or severity of adverse effects can be increased when Metamizole is combined with Omacetaxine mepesuccinate.	Withdrawn
Mizoribine	The risk or severity of adverse effects can be increased when Mizoribine is combined with Omacetaxine mepesuccinate.	Investigational
Mycophenolate mofetil	The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Mycophenolic acid	The risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Omacetaxine mepesuccinate.	Approved
Nabumetone	The risk or severity of adverse effects can be increased when Nabumetone is combined with Omacetaxine mepesuccinate.	Approved
Nadroparin	The risk or severity of adverse effects can be increased when Nadroparin is combined with Omacetaxine mepesuccinate.	Approved
Nafamostat	The risk or severity of adverse effects can be increased when Nafamostat is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Naftifine	The risk or severity of adverse effects can be increased when Naftifine is combined with Omacetaxine mepesuccinate.	Approved
Naproxen	The risk or severity of adverse effects can be increased when Naproxen is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved
NCX 4016	The risk or severity of adverse effects can be increased when NCX 4016 is combined with Omacetaxine mepesuccinate.	Investigational
Nepafenac	The risk or severity of adverse effects can be increased when Nepafenac is combined with Omacetaxine mepesuccinate.	Approved
Niflumic Acid	The risk or severity of adverse effects can be increased when Niflumic Acid is combined with Omacetaxine mepesuccinate.	Approved
Nimesulide	The risk or severity of adverse effects can be increased when Nimesulide is combined with Omacetaxine mepesuccinate.	Approved, Withdrawn
Nitroaspirin	The risk or severity of adverse effects can be increased when Nitroaspirin is combined with Omacetaxine mepesuccinate.	Investigational
Oleandrin	Anvirzel may decrease the cardiotoxic activities of Omacetaxine mepesuccinate.	Experimental
Olopatadine	The risk or severity of adverse effects can be increased when Olopatadine is combined with Omacetaxine mepesuccinate.	Approved
Olsalazine	The risk or severity of adverse effects can be increased when Olsalazine is combined with Omacetaxine mepesuccinate.	Approved
Ouabain	Ouabain may decrease the cardiotoxic activities of Omacetaxine mepesuccinate.	Approved
Oxaprozin	The risk or severity of adverse effects can be increased when Oxaprozin is combined with Omacetaxine mepesuccinate.	Approved
Oxyphenbutazone	The risk or severity of adverse effects can be increased when Oxyphenbutazone is combined with Omacetaxine mepesuccinate.	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 adverse effects can be increased when Parecoxib is combined with Omacetaxine mepesuccinate.	Approved
Pentosan Polysulfate	The risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Omacetaxine mepesuccinate.	Approved
Phenindione	The risk or severity of adverse effects can be increased when Phenindione is combined with Omacetaxine mepesuccinate.	Approved
Phenprocoumon	The risk or severity of adverse effects can be increased when Phenprocoumon is combined with Omacetaxine mepesuccinate.	Approved
Phenylbutazone	The risk or severity of adverse effects can be increased when Phenylbutazone is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved
Pimecrolimus	The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Pirfenidone	The risk or severity of adverse effects can be increased when Pirfenidone is combined with Omacetaxine mepesuccinate.	Investigational
Piroxicam	The risk or severity of adverse effects can be increased when Piroxicam is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Propacetamol	The risk or severity of adverse effects can be increased when Propacetamol is combined with Omacetaxine mepesuccinate.	Approved
Protein S human	The risk or severity of adverse effects can be increased when Protein S human is combined with Omacetaxine mepesuccinate.	Approved
PTC299	The risk or severity of adverse effects can be increased when PTC299 is combined with Omacetaxine mepesuccinate.	Investigational
Resveratrol	The risk or severity of adverse effects can be increased when Resveratrol is combined with Omacetaxine mepesuccinate.	Experimental, Investigational
Reviparin	The risk or severity of adverse effects can be increased when Reviparin is combined with Omacetaxine mepesuccinate.	Approved
Rivaroxaban	The risk or severity of adverse effects can be increased when Rivaroxaban is combined with Omacetaxine mepesuccinate.	Approved
Rofecoxib	The risk or severity of adverse effects can be increased when Rofecoxib is combined with Omacetaxine mepesuccinate.	Investigational, Withdrawn
Salicylamide	The risk or severity of adverse effects can be increased when Salicylamide is combined with Omacetaxine mepesuccinate.	Approved
Salicylic acid	The risk or severity of adverse effects can be increased when Salicylic acid is combined with Omacetaxine mepesuccinate.	Approved, Vet Approved
Salsalate	The risk or severity of adverse effects can be increased when Salsalate is combined with Omacetaxine mepesuccinate.	Approved
SRT501	The risk or severity of adverse effects can be increased when SRT501 is combined with Omacetaxine mepesuccinate.	Investigational
Sulfasalazine	The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Omacetaxine mepesuccinate.	Approved
Sulindac	The risk or severity of adverse effects can be increased when Sulindac is combined with Omacetaxine mepesuccinate.	Approved
Sulodexide	The risk or severity of adverse effects can be increased when Sulodexide is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Suprofen	The risk or severity of adverse effects can be increased when Suprofen is combined with Omacetaxine mepesuccinate.	Approved, Withdrawn
Tenoxicam	The risk or severity of adverse effects can be increased when Tenoxicam is combined with Omacetaxine mepesuccinate.	Approved
Teriflunomide	The risk or severity of adverse effects can be increased when Teriflunomide is combined with Omacetaxine mepesuccinate.	Approved
Tiaprofenic acid	The risk or severity of adverse effects can be increased when Tiaprofenic acid is combined with Omacetaxine mepesuccinate.	Approved
Tinoridine	The risk or severity of adverse effects can be increased when Tinoridine is combined with Omacetaxine mepesuccinate.	Investigational
Tolfenamic Acid	The risk or severity of adverse effects can be increased when Tolfenamic Acid is combined with Omacetaxine mepesuccinate.	Approved
Tolmetin	The risk or severity of adverse effects can be increased when Tolmetin is combined with Omacetaxine mepesuccinate.	Approved
Tranilast	The risk or severity of adverse effects can be increased when Tranilast is combined with Omacetaxine mepesuccinate.	Approved, Investigational
Trastuzumab	Trastuzumab may increase the cardiotoxic activities of Omacetaxine mepesuccinate.	Approved, Investigational
Valdecoxib	The risk or severity of adverse effects can be increased when Valdecoxib is combined with Omacetaxine mepesuccinate.	Investigational, Withdrawn
Warfarin	The risk or severity of adverse effects can be increased when Warfarin is combined with Omacetaxine mepesuccinate.	Approved
Ximelagatran	The risk or severity of adverse effects can be increased when Ximelagatran is combined with Omacetaxine mepesuccinate.	Approved, Investigational, Withdrawn
Zaltoprofen	The risk or severity of adverse effects can be increased when Zaltoprofen is combined with Omacetaxine mepesuccinate.	Approved
Zileuton	The risk or severity of adverse effects can be increased when Zileuton is combined with Omacetaxine mepesuccinate.	Approved, Investigational, Withdrawn
Zomepirac	The 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

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

Resource	Link
KEGG Drug	D08956
ChemSpider	251215
ChEBI	71019
ChEMBL	CHEMBL46286
HET	HMT
RxList	http://www.rxlist.com/synribo-drug.htm
Drugs.com	http://www.drugs.com/cdi/omacetaxine-injection.html
Wikipedia	Omacetaxine_mepesuccinate

ATC Codes

L01XX40 — Omacetaxine mepesuccinate

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Download (170 KB)

MSDS

Download (68.5 KB)

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Hematologic Tumors	1
1	Completed	Treatment	Malignancies, Hematologic / Tumors, Solid	1
1, 2	Recruiting	Other	Chronic Myeloid Leukemia (CML)	1
1, 2	Recruiting	Treatment	Acute Myeloid Leukaemias (AML)	1
1, 2	Withdrawn	Treatment	Leukemias	1
1, 2	Withdrawn	Treatment	Myelodysplastic Syndromes	1
2	Active Not Recruiting	Treatment	Leukemias	1
2	Completed	Treatment	Childhood Chronic Myelogenous Leukemia / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Chronic Phase Chronic Myelogenous Leukemia / Relapsing Chronic Myelogenous Leukemia	1
2	Completed	Treatment	Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Chronic Phase Chronic Myelogenous Leukemia	1
2	Completed	Treatment	Chronic Myeloid Leukemia (CML)	2
2	Completed	Treatment	Leukemias	3
2	Not Yet Recruiting	Treatment	AML / FLT3-ITD Mutation	1
2	Recruiting	Treatment	Acute Myelogenous Leukaemia (AML)	1
2	Recruiting	Treatment	Leukemias	1
2	Terminated	Treatment	Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Secondary Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia	1
2	Terminated	Treatment	Blast Phase / Chronic Myelocytic Leukemia / Myeloid Leukemia, Chronic, Accelerated-Phase / Myeloid Leukemia, Chronic, Chronic-Phase	1
3	Terminated	Treatment	Leukemias	1

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)
US6987103	No	2003-06-28	2023-06-28	US
USRE45128	No	1999-03-16	2019-03-16	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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

Taxonomy

Description

This compound belongs to the class of chemical entities 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

Chemical entities

Super Class

Organic compounds

Class

Alkaloids and derivatives

Sub Class

Cephalotaxus alkaloids

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

Substituents

Cephalotaxine / Cephalotaxus alkaloid skeleton / Benzazepine / Benzodioxole / Fatty acid methyl ester / Azepine / Fatty acid ester / Aralkylamine / N-alkylpyrrolidine / Benzenoid

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

tertiary alcohol, organic heteropentacyclic compound, alkaloid ester, enol ether (CHEBI:71019 )

Targets

Details

1. 50S ribosomal protein L2

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
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 ]

Details

2. 60S ribosomal protein L3

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 July 23, 2017 12:17

Get DrugBank to go!

Structure for DB04865 (Omacetaxine mepesuccinate)

Targets

References

References