IXAZOMIB


Synonyms	Ixazomib MLN-2238 MLN-9708 FREE BASE MLN2238 Ninlaro
Status
Molecule Category	Free-form
ATC	L01XG03
UNII	71050168A2


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	MXAYKZJJDUDWDS-LBPRGKRZSA-N
Smiles	CC(C)C[C@H](NC(=O)CNC(=O)c1cc(Cl)ccc1Cl)B(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

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C14H19BCl2N2O4
Molecular Weight	361.03
AlogP	None
Hydrogen Bond Acceptor	None
Hydrogen Bond Donor	None
Number of Rotational Bond	None
Polar Surface Area	None
Molecular species	None
Aromatic Rings	None
Heavy Atoms	None

Bioactivity

Mechanism of Action	Action	Reference
26S proteasome inhibitor	INHIBITOR	EMA PubMed PubMed


Protein: 26S proteasome Description: Proteasome subunit beta type-11 Organism : Homo sapiens A5LHX3 ENSG00000222028









Protein: 26S proteasome Description: 26S proteasome non-ATPase regulatory subunit 11 Organism : Homo sapiens O00231 ENSG00000108671












Protein: 26S proteasome Description: 26S proteasome non-ATPase regulatory subunit 12 Organism : Homo sapiens O00232 ENSG00000197170













Protein: 26S proteasome Description: Proteasome subunit alpha type-7 Organism : Homo sapiens O14818 ENSG00000101182











Protein: 26S proteasome Description: 26S proteasome non-ATPase regulatory subunit 3 Organism : Homo sapiens O43242 ENSG00000108344








Protein: 26S proteasome Description: 26S proteasome regulatory subunit 6A Organism : Homo sapiens P17980 ENSG00000165916













Protein: 26S proteasome Description: Proteasome subunit beta type-1 Organism : Homo sapiens P20618 ENSG00000008018













Protein: 26S proteasome Description: Proteasome subunit alpha type-1 Organism : Homo sapiens P25786 ENSG00000129084













Protein: 26S proteasome Description: Proteasome subunit alpha type-2 Organism : Homo sapiens P25787 ENSG00000106588













Protein: 26S proteasome Description: Proteasome subunit alpha type-3 Organism : Homo sapiens P25788 ENSG00000100567













Protein: 26S proteasome Description: Proteasome subunit alpha type-4 Organism : Homo sapiens P25789 ENSG00000041357













Protein: 26S proteasome Description: Proteasome subunit beta type-8 Organism : Homo sapiens P28062 ENSG00000204264










Protein: 26S proteasome Description: Proteasome subunit beta type-9 Organism : Homo sapiens P28065 ENSG00000240065










Protein: 26S proteasome Description: Proteasome subunit alpha type-5 Organism : Homo sapiens P28066 ENSG00000143106













Protein: 26S proteasome Description: Proteasome subunit beta type-4 Organism : Homo sapiens P28070 ENSG00000159377













Protein: 26S proteasome Description: Proteasome subunit beta type-6 Organism : Homo sapiens P28072 ENSG00000142507











Protein: 26S proteasome Description: Proteasome subunit beta type-5 Organism : Homo sapiens P28074 ENSG00000100804











Protein: 26S proteasome Description: 26S proteasome regulatory subunit 7 Organism : Homo sapiens P35998 ENSG00000161057













Protein: 26S proteasome Description: Proteasome subunit beta type-10 Organism : Homo sapiens P40306 ENSG00000205220









Protein: 26S proteasome Description: 26S proteasome regulatory subunit 6B Organism : Homo sapiens P43686 ENSG00000013275













Protein: 26S proteasome Description: 26S proteasome non-ATPase regulatory subunit 8 Organism : Homo sapiens P48556 ENSG00000099341













Protein: 26S proteasome Description: Proteasome subunit beta type-3 Organism : Homo sapiens P49720 ENSG00000277791













Protein: 26S proteasome Description: Proteasome subunit beta type-2 Organism : Homo sapiens P49721 ENSG00000126067













Protein: 26S proteasome Description: 26S proteasome non-ATPase regulatory subunit 7 Organism : Homo sapiens P51665 ENSG00000103035













Protein: 26S proteasome Description: 26S proteasome complex subunit SEM1 Organism : Homo sapiens P60896 ENSG00000127922











Protein: 26S proteasome Description: Proteasome subunit alpha type-6 Organism : Homo sapiens P60900 ENSG00000100902













Protein: 26S proteasome Description: 26S proteasome regulatory subunit 4 Organism : Homo sapiens P62191 ENSG00000100764













Protein: 26S proteasome Description: 26S proteasome regulatory subunit 8 Organism : Homo sapiens P62195 ENSG00000087191













Protein: 26S proteasome Description: 26S proteasome regulatory subunit 10B Organism : Homo sapiens P62333 ENSG00000100519













Protein: 26S proteasome Description: 26S proteasome non-ATPase regulatory subunit 2 Organism : Homo sapiens Q13200 ENSG00000175166













Protein: 26S proteasome Description: 26S proteasome non-ATPase regulatory subunit 6 Organism : Homo sapiens Q15008 ENSG00000163636













Protein: 26S proteasome Description: Proteasomal ubiquitin receptor ADRM1 Organism : Homo sapiens Q16186 ENSG00000130706













Protein: 26S proteasome Description: Proteasome subunit alpha-type 8 Organism : Homo sapiens Q8TAA3 ENSG00000154611









Protein: 26S proteasome Description: Proteasome subunit beta type-7 Organism : Homo sapiens Q99436 ENSG00000136930











Protein: 26S proteasome Description: 26S proteasome non-ATPase regulatory subunit 1 Organism : Homo sapiens Q99460 ENSG00000173692













Protein: 26S proteasome Description: 26S proteasome non-ATPase regulatory subunit 13 Organism : Homo sapiens Q9UNM6 ENSG00000185627

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Protease Serine protease Serine protease SK clan Serine protease S14 family	3600	5300	-	-	-
Enzyme Protease Threonine protease Threonine protease PBT clan Threonine protease T1A subfamily	-	3-9	-	-	-
Enzyme Protease Threonine protease Threonine protease PBT clan Threonine protease T1B subfamily	-	15	-	-	-
Other cytosolic protein	-	6	-	-	-
Transcription factor	-	6	-	-	-
Unclassified protein	-	15	-	-	-

Assay Description	Organism	Bioactivity
Reversible inhibition of human erythrocyte derived 20S proteasome subunit beta1 after 30 mins by fluorogenic assay	Homo sapiens	31.0 nM
Reversible inhibition of human erythrocyte derived 20S proteasome subunit beta5 after 30 mins by fluorogenic assay	Homo sapiens	3.4 nM
Inhibition of 20S proteasome beta5 subunit in human erythrocytes using Ac-WLA-AMC as substrate by fluorescence assay	Homo sapiens	3.0 nM
Inhibition of 26S proteasome beta5 subunit in human Calu6 cells using Suc-LLVY-aminoluciferin as substrate after 1hr by luminescence assay	Homo sapiens	9.0 nM
Inhibition of NFkappaB in HEK293 cells incubated for 1 hr prior to TNF-alpha challenge measured after 3 hrs by luciferase reporter gene assay relative to control	Homo sapiens	6.2 nM
Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate incubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric method	Homo sapiens	7.73 nM
Cytotoxicity against human RPMI8226 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay	Homo sapiens	55.32 nM
Cytotoxicity against human U266B1 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay	Homo sapiens	52.15 nM
Cytotoxicity against human ARH77 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay	Homo sapiens	65.5 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging	Homo sapiens	0.73 %
Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay	Homo sapiens	15.0 nM
Inhibition of 20S proteasome beta 1c (unknown origin) after 1 hr by fluorescence based assay	Homo sapiens	3.0 nM
Inhibition of 20S proteasome beta 2c (unknown origin) after 1 hr by fluorescence based assay	Homo sapiens	30.0 nM
Inhibition of 20S proteasome beta 5c (unknown origin) after 1 hr by fluorescence based assay	Homo sapiens	3.4 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	15.12 %	SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	1.564 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	20.58 %	Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	9.38 %	Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	9.38 %	Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	20.58 %

Cross References

Resources	Reference
ChEBI	90942
ChEMBL	CHEMBL2141296
DrugBank	DB09570
DrugCentral	5067
FDA SRS	71050168A2
Guide to Pharmacology	8450
PDB	6V8
PubChem	25183872
SureChEMBL	SCHEMBL3742758
ZINC	ZINC000169946773

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