Target Information

Target General Information

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Target ID

T16087

Target Name

TMPRSS6 messenger RNA (TMPRSS6 mRNA)

Synonyms

Matriptase-2

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Gene Name

TMPRSS6

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Myeloproliferative neoplasm [ICD-11: 2A20]

Thalassaemia [ICD-11: 3A50]

Function

Serine protease which hydrolyzes a range of proteins including type I collagen, fibronectin and fibrinogen. Can also activate urokinase-type plasminogen activator with low efficiency. May play a specialized role in matrix remodeling processes in liver. Through the cleavage of HJV, a regulator of the expression of the iron absorption-regulating hormone hepicidin/HAMP, plays a role in iron homeostasis.

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BioChemical Class

mRNA target

UniProt ID

TMPS6_HUMAN

EC Number

EC 3.4.21.-

Sequence

MLLLFHSKRMPVAEAPQVAGGQGDGGDGEEAEPEGMFKACEDSKRKARGYLRLVPLFVLL
ALLVLASAGVLLWYFLGYKAEVMVSQVYSGSLRVLNRHFSQDLTRRESSAFRSETAKAQK
MLKELITSTRLGTYYNSSSVYSFGEGPLTCFFWFILQIPEHRRLMLSPEVVQALLVEELL
STVNSSAAVPYRAEYEVDPEGLVILEASVKDIAALNSTLGCYRYSYVGQGQVLRLKGPDH
LASSCLWHLQGPKDLMLKLRLEWTLAECRDRLAMYDVAGPLEKRLITSVYGCSRQEPVVE
VLASGAIMAVVWKKGLHSYYDPFVLSVQPVVFQACEVNLTLDNRLDSQGVLSTPYFPSYY
SPQTHCSWHLTVPSLDYGLALWFDAYALRRQKYDLPCTQGQWTIQNRRLCGLRILQPYAE
RIPVVATAGITINFTSQISLTGPGVRVHYGLYNQSDPCPGEFLCSVNGLCVPACDGVKDC
PNGLDERNCVCRATFQCKEDSTCISLPKVCDGQPDCLNGSDEEQCQEGVPCGTFTFQCED
RSCVKKPNPQCDGRPDCRDGSDEEHCDCGLQGPSSRIVGGAVSSEGEWPWQASLQVRGRH
ICGGALIADRWVITAAHCFQEDSMASTVLWTVFLGKVWQNSRWPGEVSFKVSRLLLHPYH
EEDSHDYDVALLQLDHPVVRSAAVRPVCLPARSHFFEPGLHCWITGWGALREGGPISNAL
QKVDVQLIPQDLCSEVYRYQVTPRMLCAGYRKGKKDACQGDSGGPLVCKALSGRWFLAGL
VSWGLGCGRPNYFGVYTRITGVISWIQQVVT

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Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

IONIS-TMPRSS6-LRx

Drug Info

Phase 2

Beta thalassemia

[2]

Sapablursen

Drug Info

Phase 2

Polycythemia vera

[3]

SLN124

Drug Info

Phase 1

Beta thalassemia

[4]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

ALN-TMP

Drug Info

Preclinical

Beta thalassemia

[5]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 3 Inhibitor drugs

IONIS-TMPRSS6-LRx

Drug Info

[1]

SLN124

Drug Info

[7]

ALN-TMP

Drug Info

[5]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

References

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REF 1

Clinical pipeline report, company report or official report of Ionis Pharmaceuticals.

REF 2

ClinicalTrials.gov (NCT04059406) Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS TMPRSS6-LRx. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT05143957) A Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 702843 Administered to Patients With Phlebotomy Dependent Polycythemia Vera (PD-PV). U.S.National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT04718844) A Study Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124 in Adults With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome. U.S. National Institutes of Health.

REF 5

Targeting iron metabolism in drug discovery and delivery. Nat Rev Drug Discov. 2017 Jun;16(6):400-423.

REF 6

Clinical pipeline report, company report or official report of Ionis

REF 7

SLN124, a GalNAc-siRNA Conjugate Targeting TMPRSS6, Efficiently Prevents Iron Overload in Hereditary Haemochromatosis Type 1. Hemasphere. 2019 Oct 1;3(6):e301.

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