Target Information

Target General Information

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Target ID

T69707 (Former ID: TTDNC00646)

Target Name

Proteasome (PS)

Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 3 Target-related Diseases

Amyloidosis [ICD-11: 5D00]

Mature B-cell lymphoma [ICD-11: 2A85]

Multiple myeloma [ICD-11: 2A83]

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Approved Drug(s)

[+] 3 Approved Drugs

Bortezomib

Drug Info

Approved

Multiple myeloma

[2], [3]

Carfilzomib

Drug Info

Approved

Multiple myeloma

[1], [4]

MLN9708

Drug Info

Approved

Amyloidosis

[5], [6]

Clinical Trial Drug(s)

[+] 4 Clinical Trial Drugs

Marizomib

Drug Info

Phase 3

Glioblastoma of brain

[7]

Delanzomib

Drug Info

Phase 2

Multiple myeloma

[8]

Oprozomib

Drug Info

Phase 2

Hodgkin lymphoma

[9]

GSK3494245

Drug Info

Phase 1

Visceral leishmaniasis

[10]

Discontinued Drug(s)

[+] 1 Discontinued Drugs

PS-519

Drug Info

Terminated

Ischemia-reperfusion injury

[11]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 7 Modulator drugs

Bortezomib

Drug Info

[12]

Carfilzomib

Drug Info

[1]

MLN9708

Drug Info

[13], [14]

Delanzomib

Drug Info

[16]

Oprozomib

Drug Info

[17]

PS-519

Drug Info

[19], [20]

MG-101

Drug Info

[21], [22]

Inhibitor

[+] 2 Inhibitor drugs

Marizomib

Drug Info

[15]

GSK3494245

Drug Info

[18]

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

References

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REF 1

Nat Rev Drug Discov. 2013 Feb;12(2):87-90.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6391).

REF 3

New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.

REF 4

REF 5

REF 6

ClinicalTrials.gov (NCT02181413) A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Patients With Multiple Myeloma Following Autologous Stem Cell Transplant. U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT03345095) A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma (MIRAGE). U.S. National Institutes of Health.

REF 8

Overview of proteasome inhibitor-based anti-cancer therapies: perspective on bortezomib and second generation proteasome inhibitors versus future generation inhibitors of ubiquitin-proteasome system.Curr Cancer Drug Targets. 2014;14(6):517-36.

REF 9

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 10

ClinicalTrials.gov (NCT04504435) A Randomized, Double-blind, Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single (in Both Fed and Fasted States) Doses of GSK3494245 in Healthy Participants. U.S.National Institutes of Health.

REF 11

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009964)

REF 12

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 13

Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010 Mar 1;70(5):1970-80.

REF 14

Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells.Blood.2012 Nov 8;120(19):3958-67.

REF 15

Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets. 2011 Mar;11(3):254-84.

REF 16

Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE. Int Immunopharmacol. 2012 Jan;12(1):257-70.

REF 17

A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood. 2010 Dec 2;116(23):4906-15.

REF 18

Clinical pipeline report, company report or official report of GlaxoSmithKline

REF 19

Effect of the proteasome inhibitor MLN519 on the expression of inflammatory molecules following middle cerebral artery occlusion and reperfusion in... Neurotox Res. 2003;5(7):505-14.

REF 20

Delayed treatment with MLN519 reduces infarction and associated neurologic deficit caused by focal ischemic brain injury in rats via antiinflammato... J Cereb Blood Flow Metab. 2003 Jan;23(1):75-87.

REF 21

Covalent complexes of proteasome model with peptide aldehyde inhibitors MG132 and MG101: docking and molecular dynamics study.J Mol Model.2009 Dec;15(12):1481-90.

REF 22

Proteasome modulating agents induce rAAV2-mediated transgene expression in human intestinal epithelial cells. Biochem Biophys Res Commun. 2005 Jun 17;331(4):1392-400.

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