DescriptionCurator's Comment: Description was created based on several sources, including http://www.tarixorphan.com/ | http://www.fiercepharma.com/partnering/unigene-and-tarix-pharmaceuticals-enter-definitive-licensing-agreement-for-peptelligence
Curator's Comment: Description was created based on several sources, including http://www.tarixorphan.com/ | http://www.fiercepharma.com/partnering/unigene-and-tarix-pharmaceuticals-enter-definitive-licensing-agreement-for-peptelligence
Angiotensin (1-7) [Ang 1-7] is a 7 amino acid peptide generated predominantly from Ang II by the action of Ang-converting enzyme 2. Ang 1-7 can act as a negative modulator of aldosterone secretion in vitro and in vivo. The endogenous heptapeptide angiotensin-(1-7) (Ang-(1-7)) is a RAS component that has a central role in the alternative axis. It is generated by the
cleavage of Ang-II by the action of the angiotensin converting
enzyme 2 (ACE 2) and acts via interaction with the
G-protein coupled receptor Mas. Angiotensin (1-7) induces vasorelaxation through release of NO and prostaglandins, perhaps through activation of a non-AT1, non-AT2 receptor, Mas. Counteracts the vasoconstrictive and proliferative effects of angiotensin II and stimulates vasopressin (anti-diuretic hormone) release in vivo. Clinical uses range from treatment of cardiovascular-related diseases,
ocular pathologies, metabolic dysfunctions, brain conditions and
degenerative diseases to applications in cell differentiation and
hematopoiesis, tumor therapy, acute lung injury, fibrosis, infection,
among others. Tarix Orphan is developing TXA127 for rare neuromuscular and connective tissue diseases. TXA127 is a pharmaceutical formulation of the naturally occurring peptide, Angiotensin (1-7). TXA127 has been effective in animal models of Duchenne muscular dystrophy (DMD), Limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy MDC1A, Marfan syndrome, and Dystrophic Epidermolysis Bullosa (DEB). FDA granted rare pediatric disease designation to TXA127 from Tarix to treat recessive dystrophic epidermolysis bullosa (RDEB). TXA127 has been granted orphan drug status by FDA as a treatment for pulmonary arterial hypertension, to enhance engraftment in patients receiving a stem cell transplant, and for Myelodysplastic Syndrome (MDS). Tarix Orphan has broad IP protection for TXA127 and Orphan Drug Designations (ODDs) have been granted for DMD LGMD and DEB in the U.S., and for DMD in Europe. Tarix Orphan aims to initiate a clinical trials for both DMD and DEB in early 2018 and has an active IND for a Phase II trial in DMD, as well as Fast Track designation for DMD.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10967201
Curator's Comment: Centrally Ang-(1–7) may act as an important neuromodulator, especially in those medullary areas related with the tonic and reflex control of arterial pressure.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL3559701 |
0.83 nM [Kd] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Secondary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Sample Use Guides
Treatment of hematologic malignancies: 300mcg/kg/day, subcutaneous injection for up to 28 days
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21670420
To investigate whether Ang-(1-7) induces Mas receptor internalization, MasR-YFP transfected HEK 293T cells were incubated with 1 umol/L Ang-(1-7) during different times and the relative cellular distribution of MasR-YFP was observed by laser scanning confocal microscopy. In resting cells, MasR-YFP was mostly localized on the cell membrane and in the endoplasmic reticulum. Treatment of cells with Ang-(1-7) induced redistribution in fluorescence after 5 min stimulation changing the localization of MasR-YFP to intracellular
vesicles of various sizes, suggesting internalization of the receptor upon agonist stimulation.
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IJ3FUK8MOF
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FDA ORPHAN DRUG |
144601
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400813
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308810
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508815
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546416
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295809
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129999
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EU-Orphan Drug |
EU/3/12/1047
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412313
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411813
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345411
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402713
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DB11720
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55438
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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MOL_WEIGHT:NUMBER(CALCULATED) | CHEMICAL |
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Molecular Formula | CHEMICAL |
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