Tryptophan-Hydroxylase-Inhibitors-Modulators-MCE

1、 HYPERLINK https:/www.MedChemE/Targets/Tryptophan Hydroxylase.html Tryptophan HYPERLINK https:/www.MedChemE/Targets/Tryptophan Hydroxylase.html HYPERLINK https:/www.MedChemE/Targets/Tryptophan Hydroxylase.html HydroxylaseTryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of

2、 the biogenic monoamine serotonin(5-hydroxytryptamine, 5-HT). TPH belongs to the family of the aromatic amino acid hydroxylases, including phenylalaninehydroxylase (PAH) and tyrosine hydroxylase (TH), which all have a strict requirement for dioxygen, non-heme iron (II) andtetrahydrobiopterin (BH4).T

3、ryptophan hydroxylase is activated by phosphorylating conditions (ATP-Mg2+) in a calcium-dependent,cyclic AMP-independent manner. Two existing TPH isoforms (TPH-1 and TPH-2) are responsible for the generation of two distinctserotonergic systems in vertebrates.TPH1, predominantly expressed in the gas

4、trointestinal tract and pineal gland, mediates 5-HT biosynthesis in non-neuronal tissues,while TPH2, mainly found in the raphe nuclei of the brain stem, is accountable for the production of 5-HT in the brain. TPH-1, theprincipal enzyme for peripheral serotonin biosynthesis, provides a novel target t

5、o design anabolic agents for osteoporosis. TPH2 isa phenotypic marker for serotonin neurons and is known to be extremely labile to oxidation. As a major modulator of 5-HTneurotransmission and the stress response, TPH2 is of both pathophysiological and pharmacological significance, and is emergingas

6、a new therapeutic target for the treatment of stress disorders.www.MedChemE 1 HYPERLINK https:/www.MedChemE/Targets/Tryptophan Hydroxylase.html Tryptophan HYPERLINK https:/www.MedChemE/Targets/Tryptophan Hydroxylase.html HYPERLINK https:/www.MedChemE/Targets/Tryptophan Hydroxylase.html Hydroxylase H

7、YPERLINK https:/www.MedChemE/Targets/Tryptophan Hydroxylase.html HYPERLINK https:/www.MedChemE/Targets/Tryptophan Hydroxylase.html Inhibitors HYPERLINK https:/www.MedChemE/act-678689.html ACT-678689Cat. No.: HY-19572 HYPERLINK https:/www.MedChemE/4-Chloro-DL-phenylalanine.html Fenclonine(4-Chloro-DL

8、-phenylalanine; PCPA; CP-10188) Cat. No.: HY-B1368ACT-678689 (Compound Example 1.53.4) is atryptophan hydroxylase (TPH) inhibitor with anIC of 8 nM.50Fenclonine is a potent and irreversible inhibitorof tryptophan (Trp) hydroxylase, the rate-limitingenzyme in serotonin biosynthesis.Purity: 98%Clinica

9、l Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.92%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 500 mg, 1 g HYPERLINK https:/www.MedChemE/LP-533401.html LP-533401 HYPERLINK https:/www.MedChemE/LP-533401.html HYPERLINK https:/www.MedChemE/LP-533401_hydrochloride.html LP-533401 HY

10、PERLINK https:/www.MedChemE/LP-533401_hydrochloride.html HYPERLINK https:/www.MedChemE/LP-533401_hydrochloride.html hydrochlorideCat. No.: HY-15849 Cat. No.: HY-15849ALP-533401 is a Tryptophan hydroxylase 1inhibitor that regulates serotonin production inthe gut.LP-533401 hydrochloride is a tryptopha

11、nhydroxylase 1 inhibitor that regulates serotoninproduction in the gut.Purity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98.62%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/

12、www.MedChemE/LX-1031.html LX-1031Cat. No.: HY-13041 HYPERLINK https:/www.MedChemE/4-ethynyl-l-phenylalanine.html p-Ethynylphenylalanine(4-Ethynyl-L-phenylalanine) Cat. No.: HY-23460LX-1031 is a potent, orally available tryptophan5-hydroxylase (TPH) inhibitor that reducesserotonin (5-HT) synthesis pe

13、ripherally.p-Ethynylphenylalanine (4-Ethynyl-L-phenylalanine)is a potent, selective, reversible and competitiveinhibitor of tryptophan hydroxylase (TPH), witha K of 32.6 M.iPurity: 99.58%Clinical Data: Phase 2Size: 10 mM 1 mL, 2 mg, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 99.96%Clinical Data: No De

14、velopment ReportedSize: 10 mM 1 mL, 50 mg HYPERLINK https:/www.MedChemE/4-ethynyl-l-phenylalanine-hydrochloride.html p-Ethynylphenylalanine HYPERLINK https:/www.MedChemE/4-ethynyl-l-phenylalanine-hydrochloride.html HYPERLINK https:/www.MedChemE/4-ethynyl-l-phenylalanine-hydrochloride.html hydrochlor

15、ide HYPERLINK https:/www.MedChemE/4-ethynyl-l-phenylalanine-hydrochloride.html HYPERLINK https:/www.MedChemE/pcpa-methyl-ester-hydrochloride.html PCPA HYPERLINK https:/www.MedChemE/pcpa-methyl-ester-hydrochloride.html HYPERLINK https:/www.MedChemE/pcpa-methyl-ester-hydrochloride.html methyl HYPERLIN

16、K https:/www.MedChemE/pcpa-methyl-ester-hydrochloride.html HYPERLINK https:/www.MedChemE/pcpa-methyl-ester-hydrochloride.html ester HYPERLINK https:/www.MedChemE/pcpa-methyl-ester-hydrochloride.html HYPERLINK https:/www.MedChemE/pcpa-methyl-ester-hydrochloride.html hydrochloride(4-Ethynyl-L-phenylal

17、anine hydrochloride) Cat. No.: HY-23460A (4-Chloro-DL-phenylalanine methyl ester hydrochloride) Cat. No.: HY-101456p-Ethynylphenylalanine hydrochloride(4-Ethynyl-L-phenylalanine hydrochloride) is apotent, selective, reversible and competitiveinhibitor of tryptophan hydroxylase (TPH), witha K of 32.6

18、 M.iPCPA methyl ester hydrochloride(4-Chloro-DL-phenylalanine methyl esterhydrochloride), a reversible tryptophanhydroxylase inhibitor, is a serotonin (5-HT)synthesis inhibitor.Purity: 99.42%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 50 mgPurity: 99.89%Clinical Data: No Development Repo

19、rtedSize: 1 g HYPERLINK https:/www.MedChemE/rodatristat.html Rodatristat HYPERLINK https:/www.MedChemE/rodatristat.html HYPERLINK https:/www.MedChemE/rodatristat-ethyl.html Rodatristat HYPERLINK https:/www.MedChemE/rodatristat-ethyl.html HYPERLINK https:/www.MedChemE/rodatristat-ethyl.html ethyl(KAR

20、5417) Cat. No.: HY-120083 (KAR5585) Cat. No.: HY-101124Rodatristat (KAR5417) is a potent tryptophanhydroxylase 1 (TPH1) and TPH2 inhibitor withIC s value of 33 nM and 7 nM, respectively, and50shows robust reduction of intestinal serotonin(5-HT) levels in mice.Rodatristat ethyl (KAR5585) is a first-i

21、n-classoral tryptophan hydroxylase 1 (TPH1) Inhibitorwith nanomolar in vitro potency. Rodatristat ethylreduces the level of 5-HT and significantlyreduces pulmonary arterial hypertension (PAH).Purity: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98%Clinical

22、Data: Phase 2Size: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg2 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/telotristat.html Telotristat(LP-778902) Cat. No.: HY-13055B HYPERLINK https:/www.MedChemE/lx1606.html Telotristat HYPERLINK https:/www.MedChemE/lx1606.html HYPERLINK https:/www.MedChemE/lx1606.html ethyl(LX1032; LX1606) Cat. No.: HY-13055ATelotristat (LP-778902) is a potent tryptophanhydroxylase inhibitor with