Oprozomib

Chemical compound

None

Legal statusLegal status

Investigational drug

Identifiers

IUPAC name

N-[(2S)-3-methoxy-1-[[(2S)-3-methoxy-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide

CAS Number

935888-69-0

PubChem CID

25067547

IUPHAR/BPS

8739

ChemSpider

28528375

UNII

MZ37792Y8J

KEGG

D10318

ChEMBL

ChEMBL2103884

CompTox Dashboard (EPA)

DTXSID201025950

Chemical and physical dataFormulaC₂₅H₃₂N₄O₇SMolar mass532.61 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

COC[C@H](NC(=O)[C@H](COC)NC(=O)c1cnc(C)s1)C(=O)N[C@@H](Cc2ccccc2)C(=O)[C@@]3(C)CO3

InChI

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
Key:SWZXEVABPLUDIO-WSZYKNRRSA-N

Oprozomib^[1] (codenamed ONX 0912 and PR-047) is an orally active second-generation proteasome inhibitor developed by Proteolix, which was acquired by Onyx Pharmaceuticals, an Amgen subsidiary, in 2009. It selectively inhibits chymotrypsin-like activity of both the constitutive proteasome (PSMB5) and immunoproteasome (LMP7).^[2]

It is being investigated for the treatment of hematologic malignancies, specifically, multiple myeloma, with Phase 1b studies ongoing (as of February 16, 2016).^[3] Being an epoxyketone derivative, oprozomib is structurally related to carfilzomib and has the added benefit of being orally bioavailable. Like carfilzomib, it is active against bortezomib-resistant multiple myeloma cells.^[4]

Oprozomib was granted orphan drug status for the treatment of Waldenström's macroglobulinaemia and multiple myeloma in 2014.^[5]

References

^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed International Nonproprietary Names: List 107" (PDF). World Health Organization. p. 193. Retrieved 24 April 2016.
^ Zhou HJ, Aujay MA, Bennett MK, Dajee M, Demo SD, Fang Y, et al. (May 2009). "Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047)". Journal of Medicinal Chemistry. 52 (9): 3028–38. doi:10.1021/jm801329v. PMID 19348473.
^ "Amgen Pipeline Chart". Amgen Inc. February 16, 2016. p. 3. Retrieved 24 April 2016.
^ Chauhan D, Singh AV, Aujay M, Kirk CJ, Bandi M, Ciccarelli B, et al. (December 2010). "A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma". Blood. 116 (23): 4906–15. doi:10.1182/blood-2010-04-276626. PMC 3321748. PMID 20805366.
^ "Oprozomib - Onyx Pharmaceuticals". Adis Insight. Springer Nature Switzerland AG.

Intracellular chemotherapeutic agents / antineoplastic agents (L01)

SPs/MIs
(M phase)

Block microtubule assembly	Vinca alkaloids (Vinblastine^# Vincristine^# Vindesine Vinflunine^§ 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 (Pemetrexed Raltitrexed)
Purine	Adenosine deaminase inhibitor (Pentostatin) Halogenated/ribonucleotide reductase inhibitors (Cladribine Clofarabine Fludarabine) Nelarabine Thiopurine (Mercaptopurine^# Tioguanine^#)
Pyrimidine	Thymidylate synthase inhibitor (Capecitabine^# Carmofur Doxifluridine Floxuridine Fluorouracil^# Tegafur (+gimeracil/oteracil)) DNA polymerase inhibitor (Cytarabine^# +daunorubicin) Ribonucleotide reductase inhibitor (Gemcitabine^#) Hypomethylating agent (Azacitidine Decitabine)
Deoxyribonucleotide	Ribonucleotide reductase inhibitor (Hydroxycarbamide^#)

Topoisomerase inhibitors
(S phase)

I	Camptotheca (Belotecan Camptothecin Cositecan^† Etirinotecan pegol^† Exatecan Gimatecan Irinotecan^# Lurtotecan^‡ Rubitecan^‡ Silatecan^§ Topotecan)
II	Podophyllum (Etoposide^# Teniposide)
II+Intercalation	Anthracyclines (Aclarubicin Amrubicin^† Daunorubicin^# (+cytarabine) Doxorubicin^# Epirubicin Idarubicin Pirarubicin Valrubicin Zorubicin) Anthracenediones (Losoxantrone Mitoxantrone Pixantrone) Amsacrine Bisantrene Crisnatol Menogaril^§

Crosslinking of DNA
(CCNS)

Alkylating	Nitrogen mustards: Bendamustine^# Chlormethine Cyclophosphamide^# (Ifosfamide^# Trofosfamide) Chlorambucil^# Melphalan (Melphalan flufenamide) Prednimustine Uramustine Nitrosoureas: Carmustine Fotemustine Lomustine (Semustine) Nimustine Ranimustine Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan Treosulfan) Aziridines: Carboquone Thiotepa Triaziquone Triethylenemelamine
Platinum-based	Carboplatin^# Cisplatin^# Dicycloplatin Nedaplatin Oxaliplatin^# Satraplatin
Nonclassical	Altretamine Hydrazines (Procarbazine^#) Etoglucid Mitobronitol Pipobroman Triazenes (Dacarbazine^# Mitozolomide^§ Temozolomide)
Intercalation	Streptomyces (Dactinomycin^# Bleomycin^# Mitomycins Plicamycin)

Photosensitizers/PDT

Other

Enzyme inhibitors	FI (Tipifarnib^§) CDK inhibitors (Abemaciclib Alvocidib^† Palbociclib Ribociclib Seliciclib^†) PrI Bortezomib Carfilzomib Oprozomib Ixazomib PhI (Anagrelide) IMPDI (Tiazofurin^§) LI (Masoprocol) PARP inhibitor (Fuzuloparib) Niraparib +abiraterone acetate Olaparib Rucaparib) HDAC (Belinostat Entinostat Panobinostat Romidepsin Vorinostat) PIKI (Pi3K) (Alpelisib Copanlisib Duvelisib Idelalisib Umbralisib^‡)
Receptor antagonists	ERA (Atrasentan) Retinoid X receptor (Bexarotene) Sex steroid (Testolactone)
Other/ungrouped	Adagrasib Aflibercept Arsenic trioxide Asparagine depleters (Asparaginase^#/Pegaspargase) Axicabtagene ciloleucel Belzutifan Bexarotene Brexucabtagene autoleucel Celecoxib Ciltacabtagene autoleucel Demecolcine Denileukin diftitox Eflornithine Elesclomol^§ Elsamitrucin Enasidenib Epacadostat Eribulin Estramustine Glasdegib Idecabtagene vicleucel Imetelstat Ivosidenib Lifileucel Lonidamine Lucanthone Lurbinectedin Mitoguazone Mitotane Navitoclax Oblimersen^† Omacetaxine mepesuccinate Plitidepsin Retinoids (Alitretinoin Tretinoin^#) Selinexor Sitimagene ceradenovec Sotorasib Tagraxofusp Talimogene laherparepvec Tazemetostat Tebentafusp Tiazofurine Tigilanol tiglate Tisagenlecleucel Trabectedin Veliparib Venetoclax Verdinexor Vosaroxin