Identification
- Summary
Ixazomib is a monoclonal antibody used with other medications to treat multiple myeloma in patients who have received one other therapy already.
- Brand Names
- Ninlaro
- Generic Name
- Ixazomib
- DrugBank Accession Number
- DB09570
- Background
Ixazomib a second generation proteasome inhibitor (PI) and the first oral PI approved by the FDA in November 2015 for multiple myeloma treatment in combination with 2 other therapies (lenalidomide and dexamethasone) for patients who have received at least 1 prior therapy. It was found to have similar efficacy to bortezomib (the first PI approved for multiple myeloma therapy) in the control of myeloma growth and prevention of bone loss. Ixazomib citrate is marketed by Takeda Pharmaceuticals under the brand name Ninlaro, which is a prodrug that becomes quickly converted to its active metabolite, ixazomib, after administration.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Ixazomib (DB09570)
- Weight
- Average: 361.03
Monoisotopic: 360.081492 - Chemical Formula
- C14H19BCl2N2O4
- Synonyms
- Ixazomib
- External IDs
- MLN 2238
- MLN-2238
- MLN2238
- MLN9708
Pharmacology
- Indication
Ixazomib is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Multiple myeloma Regimen in combination with: Lenalidomide (DB00480), Dexamethasone (DB01234) •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
In vitro studies have shown ixazomib to induce apoptosis in multiple myeloma cells sensitive or resistant to other conventional therapies. In mouse xenograft models, ixazomib induced tumor growth inhibition.
- Mechanism of action
Ixazomib is an N-capped dipeptidyl leucine boronic acid which reversibly inhibits the CT-L proteolytic (β5) site of the 20S proteasome. At higher concentrations, ixazomib also seems to inhibit the proteolytic β1 and β2 subunits and to induce accumulation of ubiquitinated proteins.
- Absorption
After oral administration, the time to reach maximum concentration in plasma was 1 hour. The mean absolute oral bioavailability is 58%.
- Volume of distribution
The steady-state volume of distribution is 543 L.
- Protein binding
99%
- Metabolism
Metabolism of ixazomib is expected to be by CYP and non-CYP pathways, with no predominant CYP isozyme contribution. At higher than clinical concentrations, ixazomib was metabolized by multiple CYP isoforms with estimated relative contributions of 3A4 (42%), 1A2 (26%), 2B6 (16%), 2C8 (6%), 2D6 (5%), 2C19 (5%) and 2C9 (<1%).
- Route of elimination
62% in urine and 22% in feces.
- Half-life
Terminal half-life is 9.5 days.
- Clearance
Not Available
- Adverse Effects
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Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in <1% of patients. Ixazomib can cause fetal harm when administered to pregnant women, and therefore it should also be advised to women of reproductive age to avoid becoming pregnant on ixazomib.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Ixazomib which could result in a higher serum level. Abametapir The serum concentration of Ixazomib can be increased when it is combined with Abametapir. Abatacept The metabolism of Ixazomib can be increased when combined with Abatacept. Acalabrutinib The metabolism of Ixazomib can be decreased when combined with Acalabrutinib. Aceclofenac Aceclofenac may decrease the excretion rate of Ixazomib which could result in a higher serum level. - Food Interactions
- Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of ixazomib.
- Take on an empty stomach. Food increases the absorption of ixazomib, take ixazomib dose at least one hour before and at least two hours after food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Ixazomib citrate 46CWK97Z3K 1239908-20-3 MBOMYENWWXQSNW-AWEZNQCLSA-N - International/Other Brands
- Ninlaro
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ninlaro Capsule 3 mg/1 Oral Takeda Pharmaceuticals America, Inc. 2015-11-20 Not applicable US 
Ninlaro Capsule 3 mg/1 Oral Takeda Pharmaceuticals America, Inc. 2015-11-20 2023-10-31 US Ninlaro Capsule 2.3 mg Oral Takeda Pharma A/S 2021-02-10 Not applicable EU 
Ninlaro Capsule 2.3 mg Oral Takeda 2016-09-21 Not applicable Canada 
Ninlaro Capsule 4 mg/1 Oral Takeda Pharmaceuticals America, Inc. 2015-11-20 Not applicable US
Categories
- ATC Codes
- L01XG03 — Ixazomib
- Drug Categories
- Amino Acids
- Amino Acids, Peptides, and Proteins
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Narrow Therapeutic Index Drugs
- Proteasome Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as hippuric acids and derivatives. These are compounds containing a hippuric acid or a derivative, with a structure characterized the presence of a benzoyl group linked to the N-terminal of a glycine.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzoic acids and derivatives
- Direct Parent
- Hippuric acids and derivatives
- Alternative Parents
- N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / 2-halobenzoic acids and derivatives / 3-halobenzoic acids and derivatives / Benzoyl derivatives / Dichlorobenzenes / Aryl chlorides / Vinylogous halides / Secondary carboxylic acid amides / Boronic acids show 8 more
- Substituents
- 1,4-dichlorobenzene / 2-halobenzoic acid or derivatives / 3-halobenzoic acid or derivatives / Alkylborane / Alpha-amino acid amide / Alpha-amino acid or derivatives / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Benzoyl show 26 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 71050168A2
- CAS number
- 1072833-77-2
- InChI Key
- MXAYKZJJDUDWDS-LBPRGKRZSA-N
- InChI
- InChI=1S/C14H19BCl2N2O4/c1-8(2)5-12(15(22)23)19-13(20)7-18-14(21)10-6-9(16)3-4-11(10)17/h3-4,6,8,12,22-23H,5,7H2,1-2H3,(H,18,21)(H,19,20)/t12-/m0/s1
- IUPAC Name
- [(1R)-1-{2-[(2,5-dichlorophenyl)formamido]acetamido}-3-methylbutyl]boronic acid
- SMILES
- CC(C)C[C@H](NC(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl)B(O)O
References
- General References
- Offidani M, Corvatta L, Caraffa P, Gentili S, Maracci L, Leoni P: An evidence-based review of ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma. Onco Targets Ther. 2014 Sep 29;7:1793-800. doi: 10.2147/OTT.S49187. eCollection 2014. [Article]
- Gentile M, Offidani M, Vigna E, Corvatta L, Recchia AG, Morabito L, Morabito F, Gentili S: Ixazomib for the treatment of multiple myeloma. Expert Opin Investig Drugs. 2015;24(9):1287-98. doi: 10.1517/13543784.2015.1065250. Epub 2015 Jul 3. [Article]
- External Links
- KEGG Drug
- D10130
- PubChem Compound
- 25183872
- PubChem Substance
- 310265228
- ChemSpider
- 25027391
- BindingDB
- 50398609
- 1723735
- ChEBI
- 90942
- ChEMBL
- CHEMBL2141296
- ZINC
- ZINC000169946773
- PDBe Ligand
- 6V8
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ixazomib
- PDB Entries
- 5lf7 / 7q11 / 8qyf
- FDA label
- Download (463 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Multiple Myeloma (MM) 1 4 Completed Treatment Relapsed/Refractory Multiple Myeloma (RRMM) 1 4 Recruiting Treatment Multiple Myeloma (MM) 3 4 Withdrawn Treatment Multiple Myeloma (MM) 1 3 Active Not Recruiting Treatment Autologous Stem Cell Transplantation / Multiple Myeloma (MM) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 2.3 mg/1 Capsule Oral 3 mg/1 Capsule Oral 3.0 MG Capsule Oral 4 mg/1 Capsule Oral 4.0 MG Capsule Oral 2.3 mg Capsule Oral 3 mg Capsule Oral 4 mg Capsule Oral Capsule, coated Oral 2.3 mg Capsule, coated Oral 3 mg Capsule, coated Oral 4 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8871745 No 2014-10-28 2027-08-06 US US8530694 No 2013-09-10 2027-08-06 US US7442830 No 2008-10-28 2027-08-06 US US9175017 No 2015-11-03 2029-06-16 US US8003819 No 2011-08-23 2027-08-06 US US9233115 No 2016-01-12 2024-08-12 US US8546608 No 2013-10-01 2024-08-12 US US7687662 No 2010-03-30 2027-08-06 US US8859504 No 2014-10-14 2029-06-16 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0124 mg/mL ALOGPS logP 2.06 ALOGPS logP 2.57 Chemaxon logS -4.5 ALOGPS pKa (Strongest Acidic) 8.64 Chemaxon pKa (Strongest Basic) -1.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 98.66 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 84.56 m3·mol-1 Chemaxon Polarizability 36.3 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Gupta N, Diderichsen PM, Hanley MJ, Berg D, van de Velde H, Harvey RD, Venkatakrishnan K: Population Pharmacokinetic Analysis of Ixazomib, an Oral Proteasome Inhibitor, Including Data from the Phase III TOURMALINE-MM1 Study to Inform Labelling. Clin Pharmacokinet. 2017 Nov;56(11):1355-1368. doi: 10.1007/s40262-017-0526-4. [Article]
- Kumar SK, Buadi FK, LaPlant B, Halvorson A, Leung N, Kapoor P, Dingli D, Gertz MA, Go RS, Bergsagel PL, Lin Y, Dispenzieri A, Hwa YL, Fonder A, Hobbs M, Fonseca R, Hayman SR, Stewart AK, Lust JA, Mikhael J, Gonsalves W, Reeder C, Skacel T, Rajkumar SV, Lacy MQ: Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma. Blood Cancer J. 2018 Jul 30;8(8):70. doi: 10.1038/s41408-018-0106-3. [Article]
- Ixazomib FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Ixazomib EMA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- EMA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Ixazomib FDA Label [File]
Drug created at November 30, 2015 19:10 / Updated at February 20, 2024 23:54