Oprozomib

Oprozomib
Clinical data

Pronunciation	oh-PROZ-oh-mib
Routes of administration	Oral
ATC code	None
Legal status
Legal 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
Synonyms	O-methyl-N-(2-methyl-1,3-thiazol-5-carbonyl)-L-seryl-O-methyl-N-{(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl}-L-serinamide
CAS Number	935888-69-0
PubChem (CID)	25067547
IUPHAR/BPS	8739
ChemSpider	28528375
UNII	MZ37792Y8J
KEGG	D10318
ChEMBL	CHEMBL2103884
Chemical and physical data
Formula	C₂₅H₃₂N₄O₇S
Molar mass	532.61 g·mol⁻¹
3D model (Jmol)	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 Onyx Pharmaceuticals, an Amgen subsidiary. It is being investigated for the treatment of hematologic malignancies, specifically, multiple myeloma, with Phase 1b studies ongoing (as of February 16, 2016).^[2] Being an epoxyketone derivative, oprozomib is structurally related to carfilzomib and has the added benefit of being orally bioavailable. It selectively inhibits chymotrypsin-like activity of both the constitutive proteasome (PSMB5) and immunoproteasome (LMP7).^[3] Like carfilzomib, it is active against bortezomib-resistant multiple myeloma cells.^[4]

References

↑ "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed International Nonproprietary Names: List 107" (PDF). World Health Organization. p. 193. Retrieved 24 April 2016.
↑ "Amgen Pipeline Chart". Amgen Inc. February 16, 2016. p. 3. Retrieved 24 April 2016.
↑ Zhou, Han-Jie; Aujay, Monette A.; Bennett, Mark K.; Dajee, Maya; Demo, Susan D.; Fang, Ying; Ho, Mark N.; Jiang, Jing; Kirk, Christopher J.; Laidig, Guy J.; Lewis, Evan R.; Lu, Yan; Muchamuel, Tony; Parlati, Francesco; Ring, Eileen; Shenk, Kevin D.; Shields, Jamie; Shwonek, Peter J.; Stanton, Timothy; Sun, Congcong M.; Sylvain, Catherine; Woo, Tina M.; Yang, Jinfu (14 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.
↑ Chauhan, D; Singh, AV; Aujay, M; Kirk, CJ; Bandi, M; Ciccarelli, B; Raje, N; Richardson, P; Anderson, KC (30 August 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.

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 Cositecan^† Belotecan Gimatecan Exatecan Irinotecan Lurtotecan^‡ Silatecan^§ Topotecan Rubitecan^‡)

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

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Oprozomib

See also

References