U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H32N4O7S
Molecular Weight 532.609
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OPROZOMIB

SMILES

COC[C@H](NC(=O)[C@H](COC)NC(=O)C1=CN=C(C)S1)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)[C@@]3(C)CO3

InChI

InChIKey=SWZXEVABPLUDIO-WSZYKNRRSA-N
InChI=1S/C25H32N4O7S/c1-15-26-11-20(37-15)24(33)29-19(13-35-4)23(32)28-18(12-34-3)22(31)27-17(21(30)25(2)14-36-25)10-16-8-6-5-7-9-16/h5-9,11,17-19H,10,12-14H2,1-4H3,(H,27,31)(H,28,32)(H,29,33)/t17-,18-,19-,25+/m0/s1

HIDE SMILES / InChI
Molecular Formula C25H32N4O7S
Molecular Weight 532.609
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Oprozomib (PR-047) is an orally bioavailable derivative of carfilzomib, with similar biological activity, i.e. inhibition of the chymotrypsin-like activity of the proteasome. It inhibits the activity of the proteasome, thereby blocking the targeted proteolysis normally performed by the proteasome; this may result in an accumulation of unwanted or misfolded proteins. Disruption of various cell signaling pathways may follow, eventually leading to the induction of apoptosis and inhibition of tumor growth. Oprozomib (PR-047) is being investigated for the treatment of hematologic malignancies, specifically, multiple myeloma, with Phase I/II trial ongoing.

Originator

Proteolix
1
Curator's Comment: Proteolix was acquired by Onyx Pharmaceuticals, an Amgen subsidiary, in 2009.

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 82.0 nM [IC50]
Proteasome subunit beta type-5
6
Target ID: P28074|||Q86T01
Gene ID: 5693.0
Gene Symbol: PSMB5
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 36.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
330 mg 2 times / week multiple, oral
Highest studied dose
Dose: 330 mg, 2 times / week
Route: oral
Route: multiple
Dose: 330 mg, 2 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
DLT: Diarrhea, Hypotension...
Dose limiting toxicities:
Diarrhea (14.3%)
Hypotension (14.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
150 mg 1 times / day multiple, oral
MTD
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
240 mg 1 times / day multiple, oral
MTD
Dose: 240 mg, 1 times / day
Route: oral
Route: multiple
Dose: 240 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
DLT: Tumor lysis syndrome...
Dose limiting toxicities:
Tumor lysis syndrome (25%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
300 mg 2 times / week multiple, oral
MTD
Dose: 300 mg, 2 times / week
Route: oral
Route: multiple
Dose: 300 mg, 2 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
DLT: Hypotension...
Dose limiting toxicities:
Hypotension (14.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
90 mg 2 times / day multiple, oral
MTD
Dose: 90 mg, 2 times / day
Route: oral
Route: multiple
Dose: 90 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
DLT: Hypophosphatemia...
Dose limiting toxicities:
Hypophosphatemia (grade 3, 14.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
180 mg 1 times / day multiple, oral
Studied dose
Dose: 180 mg, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
DLT: Vomiting, Dehydration...
Dose limiting toxicities:
Vomiting (grade 3, 16.7%)
Dehydration (grade 3, 16.7%)
Hypophosphatemia (grade 3, 16.7%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
210 mg 2 times / day multiple, oral (total)
Studied dose
Dose: 210 mg, 2 times / day
Route: oral
Route: multiple
Dose: 210 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
DLT: Gastrointestinal hemorrhage, Hallucinations...
Dose limiting toxicities:
Gastrointestinal hemorrhage (grade 5, 20%)
Hallucinations (grade 3, 20%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
270 mg 1 times / day multiple, oral
Studied dose
Dose: 270 mg, 1 times / day
Route: oral
Route: multiple
Dose: 270 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
DLT: Vomiting...
Dose limiting toxicities:
Vomiting (12.5%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
AEs

AEs

AESignificanceDosePopulation
Diarrhea 14.3%
DLT
330 mg 2 times / week multiple, oral
Highest studied dose
Dose: 330 mg, 2 times / week
Route: oral
Route: multiple
Dose: 330 mg, 2 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
Hypotension 14.3%
DLT
330 mg 2 times / week multiple, oral
Highest studied dose
Dose: 330 mg, 2 times / week
Route: oral
Route: multiple
Dose: 330 mg, 2 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
Tumor lysis syndrome 25%
DLT
240 mg 1 times / day multiple, oral
MTD
Dose: 240 mg, 1 times / day
Route: oral
Route: multiple
Dose: 240 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
Hypotension 14.3%
DLT
300 mg 2 times / week multiple, oral
MTD
Dose: 300 mg, 2 times / week
Route: oral
Route: multiple
Dose: 300 mg, 2 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
Hypophosphatemia grade 3, 14.3%
DLT
90 mg 2 times / day multiple, oral
MTD
Dose: 90 mg, 2 times / day
Route: oral
Route: multiple
Dose: 90 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
Dehydration grade 3, 16.7%
DLT
180 mg 1 times / day multiple, oral
Studied dose
Dose: 180 mg, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
Hypophosphatemia grade 3, 16.7%
DLT
180 mg 1 times / day multiple, oral
Studied dose
Dose: 180 mg, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
Vomiting grade 3, 16.7%
DLT
180 mg 1 times / day multiple, oral
Studied dose
Dose: 180 mg, 1 times / day
Route: oral
Route: multiple
Dose: 180 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
Hallucinations grade 3, 20%
DLT
210 mg 2 times / day multiple, oral (total)
Studied dose
Dose: 210 mg, 2 times / day
Route: oral
Route: multiple
Dose: 210 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
Gastrointestinal hemorrhage grade 5, 20%
DLT, Disc. AE
210 mg 2 times / day multiple, oral (total)
Studied dose
Dose: 210 mg, 2 times / day
Route: oral
Route: multiple
Dose: 210 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FED
Population Size: 5
Sources:
https://pubmed.ncbi.nlm.nih.gov/26924128
Page: p.5
Vomiting 12.5%
DLT
270 mg 1 times / day multiple, oral
Studied dose
Dose: 270 mg, 1 times / day
Route: oral
Route: multiple
Dose: 270 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: multiple myeloma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/31142508
Page: p.4910
Sourcing

Sourcing

Vendor/AggregatorIDURL
1PlusChem LLC
1P00GULT
https://www.1pchem.com/search?query=1P00GULT
AK Scientific
2614AH
https://aksci.com/item_detail.php?cat=2614AH
AK Scientific
SYN5719
https://aksci.com/item_detail.php?cat=SYN5719
AKOS
AKOS028109171
http://akoscompounds.de/catalogue/AKosSamplesiSSretrieval.php?GUID=4e4caa52-3dca-4da0-b75a-caeae59e1096&IDNUMBERS=AKOS028109171
AOBIOUS INC
AOB87341
http://aobious.com/aobious/search?search_query=AOB87341
AstaTech
40576
http://astatechinc.com/CPSResult.php?CRNO=40576
BLD Pharm
BD631034
http://www.bldpharm.com/search/Search.html?keyword=BD631034
BOC Sciences
935888-69-0
http://www.bocsci.com/description.asp?cas=935888-69-0
Cayman Chemical
16269
http://www.caymanchem.com/app/template/Product.vm/catalog/16269
Chem Scene
CS-2767
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2767
ChemShuttle
141848
https://www.chemshuttle.com/catalogsearch/result/?q=141848
KeyOrganics
AS-17020
http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17020
MedChem Express
HY-12113
https://www.medchemexpress.com/search.html?q=HY-12113&ft=&fa=&fp=
MolPort
MolPort-028-720-441
https://www.molport.com/shop/molecule-link/MolPort-028-720-441
MolPort
MolPort-035-395-758
https://www.molport.com/shop/molecule-link/MolPort-035-395-758
Molnova
M16697
https://www.molnova.com/en/serch-list.html?keywords=M16697
Selleck Chemicals
S7049
http://www.selleckchem.com/search.html?searchDTO.searchParam=S7049
ShangHai Biochempartner
BCP000868
http://www.biochempartner.com/search_BCP000868
ShangHai Biochempartner
BCP07603
http://www.biochempartner.com/search_BCP07603
TargetMol
T6041
https://www.targetmol.com/search?keyword=T6041
Toronto Research Chemicals
O669700
https://www.trc-canada.com/product-detail/?CatNum=O669700
eMolecules
46301158
https://orderbb.emolecules.com/search/#?query=46301158
eMolecules
49383347
https://orderbb.emolecules.com/search/#?query=49383347
mcule
MCULE-6520091555
https://mcule.com/MCULE-6520091555/
mcule
MCULE-8434983414
https://mcule.com/MCULE-8434983414/
PubMed

PubMed

TitleDatePubMed
Patents

Patents

US20140113855
1
US20160213610
1

Sample Use Guides

In Vivo Use Guide
Patients enrolled will receive oprozomib tablets once daily either on days 1-5 (QDx5 schedule) or on days 1, 2, 8, and 9 (QDx2 weekly schedule) of the 14-day treatment cycle.
Route of Administration: Oral
In Vitro Use Guide
The ability of oprozomib (ONX 0912) versus carfilzomib to inhibit chymotrypsin-like (CT-L) proteasome activity using 2 different multiple myeloma (MM) cell lines. MM.1S and MM.1R were treated with ONX 0912 (3 nM) and carfilzomib (5 nM), and protein lysates were subjected to proteasome activity assays using CT-L–specific fluorogenic peptide substrates. Results showed that ONX 0912 triggers a significant and similar degree of proteasome activity inhibition as carfilzomib (P<0.05 for both cell lines).
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:30:38 GMT 2023
Edited
by admin
on Sat Dec 16 01:30:38 GMT 2023
Record UNII
MZ37792Y8J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OPROZOMIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
O-METHYL-N-((2-METHYLTHIAZOL-5-YL)CARBONYL)-L-SERYL-O-METHYL-N-((1S)-1-BENZYL-2-((2R)- 2-METHYLOXIRAN-2-YL)-2-OXOETHYL)-L-SERINAMIDE
Systematic Name English
ONX-0912
Code English
oprozomib [INN]
Common Name English
PR-047
Common Name English
ONX 0912
Code English
OPROZOMIB [USAN]
Common Name English
Oprozomib [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 449614
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
FDA ORPHAN DRUG 443614
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
NCI_THESAURUS C2160
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
Code System Code Type Description
EVMPD
SUB126055
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
PUBCHEM
25067547
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
FDA UNII
MZ37792Y8J
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
CAS
935888-69-0
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
EPA CompTox
DTXSID201025950
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
USAN
YY-148
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
NCI_THESAURUS
C91388
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
WIKIPEDIA
Oprozomib
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
INN
9597
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
DRUG BANK
DB11991
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
SMS_ID
100000151658
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
ChEMBL
CHEMBL2103884
Created by admin on Sat Dec 16 01:30:38 GMT 2023 , Edited by admin on Sat Dec 16 01:30:38 GMT 2023
PRIMARY
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
20S PROTEASOME
TARGET -> INHIBITOR
Related Record Type Details
Structure of N-((1S)-2-(((1S)-2-(((1S)-1-BENZYL-2-((2R)-2-METHYLOXIRAN-2-YL)-2-OXO-ETHYL)AMINO)-1-(METHOXYMETHYL)-2-OXO-ETHYL)AMINO)-1-(HYDROXYMETHYL)-2-OXO-ETHYL)-2-METHYL-THIAZOLE-5-CARBOXAMIDE
METABOLITE -> PARENT
Structure of N-((1S)-2-(((1S)-2-(((1S)-1-BENZYL-2-((2R)-2-METHYLOXIRAN-2-YL)-2-OXO-ETHYL)AMINO)-1-(HYDROXYMETHYL)-2-OXO-ETHYL)AMINO)-1-(METHOXYMETHYL)-2-OXO-ETHYL)-2-METHYL-THIAZOLE-5-CARBOXAMIDE
METABOLITE -> PARENT
Structure of (2S)-2-AMINO-1-((2R)-2-METHYL-2-OXIRANYL)-3-PHENYL-1-PROPANONE
METABOLITE -> PARENT
Structure of (2R,4S)-4-AMINO-1,2-DIHYDROXY-2-METHYL-5-PHENYL-PENTAN-3-ONE
METABOLITE -> PARENT
Structure of (2S)-3-METHOXY-2-((2-METHYLTHIAZOLE-5-CARBONYL)AMINO)PROPANOIC ACID
METABOLITE -> PARENT
Related Record Type Details
Structure of OPROZOMIB
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