Ixazomib

Ixazomib
Systematic (IUPAC) name

N²-(2,5-Dichlorobenzoyl)-N-[(1R)-1-(dihydroxyboryl)-3-methylbutyl]glycinamide
Clinical data
Trade names	Ninlaro
AHFS/Drugs.com	entry
Routes of administration	Oral (capsules)
Legal status
Legal status	US: ℞-only ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	58%^[1]
Protein binding	99%
Metabolism	Hepatic (CYP: 3A4 (42%), 1A2 (26%), 2B6 (16%) and others)
Biological half-life	9.5 days
Excretion	Urine (62%), feces (22%)
Identifiers
CAS Number	1072833-77-2
ATC code	L01XX50 (WHO)
PubChem	CID 25183872
ChemSpider	25027391
UNII	71050168A2
KEGG	D10130
ChEBI	CHEBI:90942^Y
Synonyms	MLN2238
Chemical data
Formula	C₁₄H₁₉BCl₂N₂O₄
Molar mass	361.03 g·mol⁻¹
SMILES B([C@H](CC(C)C)NC(=O)CNC(=O)c1cc(ccc1Cl)Cl)(O)O
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 Key:MXAYKZJJDUDWDS-LBPRGKRZSA-N

Ixazomib (trade name Ninlaro) is a drug for the treatment of multiple myeloma, developed by Takeda. It acts as a proteasome inhibitor and has orphan drug status in the US.

On November 20, 2015, the U.S. Food and Drug Administration approved ixazomib for use in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma after at least one prior therapy.^[2]

Mechanism

Ixazomib is a peptide analogue that reversibly inhibits the protein proteasome subunit beta type-5 (PSMB5), which is part of the 20S proteasome complex.^[3]

Chemistry

Ixazomib citrate—a prodrug for ixazomib

Ixazomib citrate is a prodrug which is rapidly hydrolyzes under physiological conditions to its biologically active form, ixazomib.^[1]

References

1 2 "Ninlaro (ixazomib) Capsules, for Oral Use. Full Prescribing Information" (PDF). NINLARO (ixazomib) For Healthcare Professionals. Takeda Pharmaceutical Company Limited. Retrieved 21 November 2015.
↑ "Press Announcements — FDA approves Ninlaro, new oral medication to treat multiple myeloma". U.S. Food and Drug Administration. Retrieved 24 April 2016.
↑ KEGG: Ixazomib

Intracellular chemotherapeutic agents / antineoplastic agents (L01)

SPs/MIs
(M phase)

Block microtubule assembly	Vinca alkaloids (Vinblastine^# Vincristine^# Vinflunine^§ Vindesine Vinorelbine)

Block microtubule disassembly	Taxanes (Cabazitaxel Docetaxel^# Larotaxel Ortataxel^† Paclitaxel^# Tesetaxel) Epothilones (Ixabepilone)

DNA replication
inhibitor

DNA precursors/
antimetabolites
(S phase)

Folic acid	Dihydrofolate reductase inhibitor (Aminopterin Methotrexate^# Pemetrexed Pralatrexate) Thymidylate synthase inhibitor (Raltitrexed Pemetrexed)

Purine	Adenosine deaminase inhibitor (Pentostatin) Halogenated/ribonucleotide reductase inhibitors (Cladribine Clofarabine Fludarabine) Nelarabine Thiopurine (Thioguanine^# Mercaptopurine^#)

Pyrimidine	Thymidylate synthase inhibitor (Fluorouracil^# Capecitabine Tegafur (+gimeracil/oteracil) Carmofur Floxuridine) DNA polymerase inhibitor (Cytarabine^#) Ribonucleotide reductase inhibitor (Gemcitabine) Hypomethylating agent (Azacitidine Decitabine)

Deoxyribonucleotide	Ribonucleotide reductase inhibitor (Hydroxycarbamide)

Topoisomerase inhibitors
(S phase)

I	Camptotheca (Camptothecin Topotecan Irinotecan Rubitecan^‡ Belotecan)

II	Podophyllum (Etoposide^# Teniposide)

II+Intercalation	Anthracyclines (Aclarubicin Daunorubicin^# Doxorubicin^# Epirubicin Idarubicin Amrubicin^† Pirarubicin Valrubicin Zorubicin) Anthracenediones (Mitoxantrone Pixantrone)

Crosslinking of DNA
(CCNS)

Alkylating	Nitrogen mustards: Mechlorethamine Cyclophosphamide^# (Ifosfamide Trofosfamide) Chlorambucil^# (Melphalan Prednimustine) Bendamustine Uramustine Estramustine Nitrosoureas: Carmustine Lomustine (Semustine) Fotemustine Nimustine Ranimustine Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan Treosulfan) Aziridines: Carboquone ThioTEPA Triaziquone Triethylenemelamine

Platinum-based	Carboplatin Cisplatin Dicycloplatin Nedaplatin Oxaliplatin Satraplatin

Nonclassical	Hydrazines (Procarbazine^#) Triazenes (Dacarbazine^# Temozolomide) Altretamine Mitobronitol Pipobroman

Intercalation	Streptomyces (Actinomycin^# Bleomycin^# Mitomycin Plicamycin)

Photosensitizers/PDT

Other

Enzyme inhibitors	FI (Tipifarnib^§) CDK inhibitors (Alvocidib^† Seliciclib^† Palbociclib) PrI Bortezomib Carfilzomib Ixazomib PhI (Anagrelide) IMPDI (Tiazofurin^§) LI (Masoprocol) PARP inhibitor (Olaparib) HDAC (Belinostat Panobinostat Romidepsin Vorinostat) PIKI (Idelalisib)

Receptor antagonists	ERA (Atrasentan) Retinoid X receptor (Bexarotene) Sex steroid (Testolactone)

Other/ungrouped	Amsacrine Trabectedin Retinoids (Alitretinoin Tretinoin) Arsenic trioxide Asparagine depleters (Asparaginase^#/Pegaspargase) Celecoxib Demecolcine Elesclomol^§ Elsamitrucin Etoglucid Lonidamine Lucanthone Mitoguazone Mitotane Oblimersen^† Omacetaxine mepesuccinate Eribulin

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

This article is issued from Wikipedia - version of the Sunday, April 24, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.