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Ixazomib

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Also known as MLN-2238MLN-9708 FREE BASEMLN2238SID124955652IXAZOMIB (MLN2238)Ninlarolxazomib

Summary

Ixazomib (CHEMBL2141296) is an approved small-molecule orphan drug (ATC L01XG03) targeting PSMB5; indicated across 21 conditions including neoplasm and plasma cell myeloma; with CIViC clinical evidence for 1 variant-indication association (e.g. KRAS Mutation in colorectal cancer).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01XG03
  • Targets: 1 (PSMB5)
  • Indications: 21 conditions
  • Clinical trials: 101
  • Precision-oncology evidence (CIViC): 1 variant–indication association
  • Chemistry: 361 Da · C14H19BCl2N2O4

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL2141296
NameIxazomib
TypeSmall molecule
Max phase3
FDA approvedyes
PubChem CID25183872
ChEBICHEBI:90942
ATCL01XG03
Molecular formulaC14H19BCl2N2O4
Molecular weight361
InChIKeyMXAYKZJJDUDWDS-LBPRGKRZSA-N

SMILES: B([C@H](CC(C)C)NC(=O)CNC(=O)C1=C(C=CC(=C1)Cl)Cl)(O)O

IUPAC name: [(1R)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid

ChEBI definition: A glycine derivative that is the amide obtained by formal condensation of the carboxy group of N-(2,5-dichlorobenzoyl)glycine with the amino group of [(1R)-1-amino-3-methylbutyl]boronic acid. The active metabolite of ixazomib citrate, it is used in combination therapy for treatment of multiple myeloma.

Pharmacological roles (ChEBI): apoptosis inducer, orphan drug, proteasome inhibitor, antineoplastic agent.

Other ChEBI roles (chemical / environmental): drug metabolite.

Also known as: Ixazomib, MLN-2238, MLN-9708 FREE BASE, MLN2238, SID124955652, IXAZOMIB, IXAZOMIB (MLN2238), Ninlaro, ixazomib, Ixazomib (MLN2238), lxazomib

Parent form; salt/anhydrous children: CHEMBL5171825

Patent coverage: 2,508 distinct patent families (6,022 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 4,143 (69%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
PSMB5proteasome 20S subunit beta 5Inhibition9.0395% (common-essential)P28074

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: ATP-dependent Clp protease proteolytic subunit, Nuclear factor NF-kappa-B complex, 3’,5’-cyclic-AMP phosphodiesterase 4A, Proteasome Macropain subunit, NACHT, LRR and PYD domains-containing protein 3, 20S proteasome, Proteasome component C5, Proteasome Macropain subunit MB1.

Bioactivity

ChEMBL activities: 20 potent at pChembl ≥ 5 of 21 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PSMB58.54IC502.88nMCHEMBL_ACT_24746485
PSMB58.52IC503nMCHEMBL_ACT_14526780
PSMB18.52IC503nMCHEMBL_ACT_19258335
PSMB58.47IC503.4nMCHEMBL_ACT_12135824
PSMB58.47IC503.4nMCHEMBL_ACT_19258355
PSMB58.47IC503.4nMCHEMBL_ACT_24972785
NFKB18.21IC506.2nMCHEMBL_ACT_14526844
PSMB118.19IC506.5nMCHEMBL_ACT_25710572
PSMB58.11IC507.73nMCHEMBL_ACT_18664337
PSMB58.05IC509nMCHEMBL_ACT_14526812
PSMB117.82IC5015nMCHEMBL_ACT_19057789
PSMB117.62IC5024.2nMCHEMBL_ACT_25920791
PSMB27.52IC5030nMCHEMBL_ACT_19258345
PSMB17.51IC5031nMCHEMBL_ACT_12135816
PSMB17.51IC5031nMCHEMBL_ACT_24972770
Q8R4B86.7IC50199.5nMCHEMBL_ACT_24746453
PSMB25.46IC503500nMCHEMBL_ACT_12135820
PSMB25.46IC503500nMCHEMBL_ACT_24972780
Q2G0365.44EC503600nMCHEMBL_ACT_19261590
Q2G0365.28IC505300nMCHEMBL_ACT_19261576

Target pathways

Aggregated over 1 target gene(s): PSMB5.

Top Reactome pathways

68 total, by targets touching each:

PathwayTargetsGenes
Activation of NF-kappaB in B cells1PSMB5
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha1PSMB5
ER-Phagosome pathway1PSMB5
Cross-presentation of soluble exogenous antigens (endosomes)1PSMB5
Autodegradation of Cdh1 by Cdh1:APC/C1PSMB5
SCF-beta-TrCP mediated degradation of Emi11PSMB5
APC/C:Cdc20 mediated degradation of Securin1PSMB5
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G11PSMB5
Cdc20:Phospho-APC/C mediated degradation of Cyclin A1PSMB5
Vpu mediated degradation of CD41PSMB5
Vif-mediated degradation of APOBEC3G1PSMB5
SCF(Skp2)-mediated degradation of p27/p211PSMB5
Degradation of beta-catenin by the destruction complex1PSMB5
Downstream TCR signaling1PSMB5
Regulation of activated PAK-2p34 by proteasome mediated degradation1PSMB5
Separation of Sister Chromatids1PSMB5
FCERI mediated NF-kB activation1PSMB5
Autodegradation of the E3 ubiquitin ligase COP11PSMB5
Regulation of ornithine decarboxylase (ODC)1PSMB5
ABC-family protein mediated transport1PSMB5
AUF1 (hnRNP D0) binds and destabilizes mRNA1PSMB5
Asymmetric localization of PCP proteins1PSMB5
Degradation of AXIN1PSMB5
Degradation of DVL1PSMB5
Hedgehog ligand biogenesis1PSMB5
Hh mutants are degraded by ERAD1PSMB5
Dectin-1 mediated noncanonical NF-kB signaling1PSMB5
CLEC7A (Dectin-1) signaling1PSMB5
Degradation of GLI1 by the proteasome1PSMB5
Degradation of GLI2 by the proteasome1PSMB5

Dominant GO biological processes

GO termTargets
proteolysis1
response to oxidative stress1
proteasomal ubiquitin-independent protein catabolic process1
proteasome-mediated ubiquitin-dependent protein catabolic process1
proteasome assembly1
obsolete proteolysis involved in protein catabolic process1

Indications & clinical

Indications

21 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
neoplasm4MONDO:0005070EFO:0000616
plasma cell myeloma3MONDO:0009693EFO:0001378
plasmacytoma3MONDO:0005615EFO:0006738
hereditary amyloidosis3MONDO:0018634MONDO:0019438
mantle cell lymphoma2MONDO:0018876EFO:1001469
leukemia2MONDO:0005059EFO:0000565
chronic kidney disease2MONDO:0005300EFO:0003884
Waldenstrom macroglobulinemia2MONDO:0100280EFO:0009441
autoimmune thrombocytopenic purpura2MONDO:0008558EFO:0007160
autoimmune hemolytic anemia2MONDO:0020108EFO:1001264
follicular lymphoma2MONDO:0018906MONDO:0018906
hematopoietic and lymphoid system neoplasm2MONDO:0002334MONDO:0044881
lymphoma1MONDO:0005062EFO:0000574
renal cell carcinoma1MONDO:0005086EFO:0000681
HIV infectious disease1MONDO:0005109EFO:0000764
acute myeloid leukemia1MONDO:0018874EFO:0000222
triple-negative breast carcinoma1MONDO:0005494EFO:0005537
lupus nephritis1MONDO:0005556EFO:0005761
acute lymphoblastic leukemia1MONDO:0004967EFO:0000220

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 101.

Phase distribution

PhaseTrials
PHASE242
PHASE1/PHASE223
PHASE119
PHASE39
PHASE45
Not specified2
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05722405PHASE4RECRUITINGIxazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT03173092PHASE4TERMINATEDA Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03416374PHASE4COMPLETEDA Study to Evaluate the Efficacy and Safety of Ixazomib in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Initially Treated With an Injection of Proteasome Inhibitor-Based Therapy
NCT04217967PHASE4COMPLETEDIxazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT05183139PHASE4WITHDRAWNA Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT03562169PHASE3RECRUITINGThe Role of Ixazomib in Autologous Stem Cell Transplant in Relapsed Myeloma - Myeloma XII (ACCoRd)
NCT03651128PHASE3ACTIVE_NOT_RECRUITINGEfficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)
NCT01564537PHASE3COMPLETEDA Phase 3 Study Comparing Oral Ixazomib Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma
NCT01659658PHASE3TERMINATEDStudy of Dexamethasone Plus IXAZOMIB (MLN9708) or Physicians Choice of Treatment in Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis
NCT01850524PHASE3COMPLETEDIXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma
NCT02312258PHASE3COMPLETEDA Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT)
NCT02516423PHASE3UNKNOWNIxazomib Citrate, Lenalidomide, Dexamethasone, and Zoledronic Acid or Zoledronic Acid Alone After Radiation Therapy in Treating Patients With Solitary Plasmacytoma of Bone
NCT03748953PHASE3COMPLETEDStudy of Oral Ixazomib Maintenance Therapy After Initial Therapy in Participants With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation (SCT)
NCT05675319PHASE3TERMINATEDAllogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy
NCT02253316PHASE2ACTIVE_NOT_RECRUITINGPhase II Study of IRD (Ixazomib, Lenalidomide, Dexamethasone) Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma
NCT02343042PHASE1/PHASE2ACTIVE_NOT_RECRUITINGSelinexor and Backbone Treatments of Multiple Myeloma Patients
NCT03225417PHASE1/PHASE2ACTIVE_NOT_RECRUITINGIxazomib in the Prophylaxis of Chronic Graft-versus-host Disease.
NCT03376672PHASE2ACTIVE_NOT_RECRUITINGIxazomib Plus Lenalidomide Plus Dexamethasone for Newly Diagnosed Myeloma Patients
NCT03587662PHASE2ACTIVE_NOT_RECRUITINGIxazomib, Gemcitabine, and Doxorubicin in Treating Patients With Locally Advanced or Metastatic Kidney Cancer
NCT03616782PHASE2RECRUITINGIxazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma(MCL)
NCT03618537PHASE2ACTIVE_NOT_RECRUITINGIxazomib Maintenance Study in Patients With AL Amyloidosis
NCT03763162PHASE2ACTIVE_NOT_RECRUITINGDaratumumab, Bortezomib, and Dexamethasone Followed by Daratumumab, Ixazomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
NCT03817320PHASE1/PHASE2ACTIVE_NOT_RECRUITINGPO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
NCT03942224PHASE2ACTIVE_NOT_RECRUITINGDaratumumab, Ixazomib, & Dexamethasone or Daratumumab, Bortezomib, & Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
NCT04009109PHASE2ACTIVE_NOT_RECRUITINGStudy of Lenalidomide/Ixazomib/Dexamethasone/Daratumumab in Transplant-Ineligible Patients With Newly Diagnosed MM
NCT04052880PHASE2ACTIVE_NOT_RECRUITINGStudy of SubQ Dara With Dose-Attenuated Bortezomib, Lenalidomide, Dexamethasone in Elderly NDMM
NCT04068597PHASE1/PHASE2RECRUITINGStudy to Evaluate CCS1477 (Inobrodib) in Haematological Malignancies
NCT04094961PHASE1/PHASE2ACTIVE_NOT_RECRUITINGIxazomib + Pomalidomide + Dexamethasone In MM
NCT04998786PHASE2ACTIVE_NOT_RECRUITINGA Multi-center Open-label Phase 2 Study of Ixazomib, Iberdomide and Dexamethasone in Elderly Patients With Multiple Myeloma at First Relapse.
NCT05451771PHASE1/PHASE2RECRUITINGVenetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Amyloidosis
NCT01217957PHASE1/PHASE2COMPLETEDA Study of Ixazomib Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
NCT01335685PHASE1/PHASE2COMPLETEDStudy of Oral Ixazomib in Combination With Melphalan and Prednisone in Participants With Newly Diagnosed Multiple Myeloma
NCT01383928PHASE1/PHASE2COMPLETEDStudy of Oral IXAZOMIB in Combination With Lenalidomide and Dexamethasone in Participants With Newly Diagnosed Multiple Myeloma
NCT01939899PHASE2COMPLETEDPhase 2 Study of Oral IXAZOMIB in Adult Participants With Relapsed and/or Refractory Follicular Lymphoma
NCT02004275PHASE1/PHASE2UNKNOWNPomalidomide and Dexamethasone With or Without Ixazomib in Treating Patients With Relapsed Multiple Myeloma
NCT02030405PHASE2TERMINATEDIxazomib (MLN9708) in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT02046070PHASE2COMPLETEDPhase 2 Study to Evaluate the Oral Combination of Ixazomib (MLN9708) With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma
NCT02302846PHASE2TERMINATEDStudy of MLN9708 as Maintenance Therapy for Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS) in Remission
NCT02400437PHASE2COMPLETEDTrial of Ixazomib, Dexamethasone and Rituximab in Patients With Untreated Waldenstrom’s Macroglobulinemia
NCT02410694PHASE2COMPLETEDIxazomib in Combination With Thalidomide - Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
KRAS MutationColorectal CancerResistanceIxazomibCIViC DEID1182

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

12 molecules share ≥1 primary target. Top 12 by shared-target count:

MoleculeSourceStatusShared targets
CARFILZOMIBChEMBL + PubChemPhase 4 (approved)PSMB5
BORTEZOMIBChEMBLPhase 4 (approved)PSMB5
VINBLASTINEChEMBLPhase 4 (approved)PSMB5
CURCUMINChEMBLPhase 3PSMB5
EPIGALOCATECHIN GALLATEChEMBLPhase 3PSMB5
MARIZOMIBChEMBLPhase 3PSMB5
QUERCETINChEMBLPhase 3PSMB5
DELANZOMIBChEMBLPhase 2PSMB5
GENISTEINChEMBLPhase 2PSMB5
LUTEOLINChEMBLPhase 2PSMB5
OPROZOMIBChEMBLPhase 2PSMB5
ZETOMIPZOMIBChEMBLPhase 2PSMB5

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot