Telotristat ethyl | CAS#1033805-22-9 | TPH inhibitor

MedKoo Cat#: 326843 | Name: Telotristat ethyl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Telotristat ethyl, also known as LX 1032 or LX 1606, is an oral serotonin synthesis inhibitor or peripheral tryptophan hydroxylase (TPH) inhibitor . Telotristat etiprate has activity in controlling diarrhea associated with carcinoid syndrome. LX1606 acts by inhibiting the enzyme tryptophan hydoxylase (TPH) and reduces serotonin production both inside and outside the GI tract without affecting brain serotonin levels. TPH is the rate-limiting enzyme involved in serotonin biosynthesis and is present in metastatic carcinoid tumor cells.

Chemical Structure

Telotristat ethyl

CAS#1033805-22-9 (ethyl)

Theoretical Analysis

MedKoo Cat#: 326843

Name: Telotristat ethyl

CAS#: 1033805-22-9 (ethyl)

Chemical Formula: C27H26ClF3N6O3

Exact Mass: 574.1707

Molecular Weight: 574.99

Elemental Analysis: C, 56.40; H, 4.56; Cl, 6.17; F, 9.91; N, 14.62; O, 8.35

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 4,250.00	Ready to ship
2g	USD 6,450.00	Ready to ship

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Related CAS #

1137608-69-5 (etiprate) 1033805-22-9 (ethyl) 1033805-28-5 (acid) 1374745-52-4 (besilate)

Synonym

LX 1032; LX-1032; LX1032; LX 1606; LX1606; LX-1606; Telotristat ethyl; Xermelo.

IUPAC/Chemical Name

ethyl (S)-2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate

InChi Key

MDSQOJYHHZBZKA-GBXCKJPGSA-N

InChi Code

InChI=1S/C27H26ClF3N6O3/c1-3-39-25(38)20(32)12-16-4-6-17(7-5-16)21-14-23(35-26(33)34-21)40-24(27(29,30)31)19-9-8-18(28)13-22(19)37-11-10-15(2)36-37/h4-11,13-14,20,24H,3,12,32H2,1-2H3,(H2,33,34,35)/t20-,24+/m0/s1

SMILES Code

O=C(OCC)[C@@H](N)CC1=CC=C(C2=NC(N)=NC(O[C@H](C3=CC=C(Cl)C=C3N4N=C(C)C=C4)C(F)(F)F)=C2)C=C1

Appearance

Waxy or sticky or semi-solid

Purity

>97% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Related CAS# CAS#1033805-22-9 (Telotristat ethyl) CAS#1033805-28-5 (Telotristat) CAS#1137608-69-5 (Telotristat etiprate)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A21T06K10

QC Data

View QC data: current batch, Lot#A21T06K10

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Telotristat ethyl (LX1032) is an inhibitor of tryptophan hydroxylase that reduces serotonin production.

In vitro activity:

TBD

In vivo activity:

The effect of LX1606 in an acute model of DSS-induced experimental colitis was investigated using a prophylactic treatment strategy (Fig. 2A). Treatment of colitic mice with LX1606 beginning 1 day prior to DSS administration resulted in significantly lower clinical disease activity scores (based on weight loss, fecal blood, and stool consistency) (Fig. 2B). Significantly lower macroscopic scores (based on fecal blood and consistency, rectal bleeding, and erythema) were also observed in LX1606-treated mice compared with vehicle-treated mice on day 5 post-DSS-induced colitis (Fig. 2C). H&E-stained colon cross sections of mice that received DSS and were treated with vehicle displayed distortion of epithelial cell architecture, increased leukocyte infiltration, loss of goblet cells, and significant thickening of the muscularis mucosa layer. In mice that received LX1606, histological damage scores were significantly less severe compared with control mice on day 5 post-DSS induction (Fig. 2D). Decrease in colitis severity was associated with significantly lower colonic MPO activity and lower levels of proinflammatory cytokines (IL-1β, IL-6) (Fig. 2, E–G). Reference: Gut. 2014 Jun;63(6):928-37. https://pubmed.ncbi.nlm.nih.gov/23749550/

	Solvent	mg/mL	mM
Solubility
	DMSO	101.5	176.53

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 574.99 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Kim JJ, Wang H, Terc JD, Zambrowicz B, Yang QM, Khan WI. Blocking peripheral serotonin synthesis by telotristat etiprate (LX1032/LX1606) reduces severity of both chemical- and infection-induced intestinal inflammation. Am J Physiol Gastrointest Liver Physiol. 2015 Sep 15;309(6):G455-65. doi: 10.1152/ajpgi.00299.2014. Epub 2015 Jul 23. PMID: 26206858. 2. Margolis KG, Stevanovic K, Li Z, Yang QM, Oravecz T, Zambrowicz B, Jhaver KG, Diacou A, Gershon MD. Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut. 2014 Jun;63(6):928-37. doi: 10.1136/gutjnl-2013-304901. Epub 2013 Jun 7. PMID: 23749550; PMCID: PMC4034681.

In vitro protocol:

TBD

In vivo protocol:

1: Lamarca A, Barriuso J, McNamara MG, Hubner RA, Valle JW. Telotristat ethyl: a new option for the management of carcinoid syndrome. Expert Opin Pharmacother. 2016 Dec;17(18):2487-2498. doi: 10.1080/14656566.2016.1254191. Epub 2016 Nov 16. PMID: 27817224. 2: Kulke MH, Hörsch D, Caplin ME, Anthony LB, Bergsland E, Öberg K, Welin S, Warner RR, Lombard-Bohas C, Kunz PL, Grande E, Valle JW, Fleming D, Lapuerta P, Banks P, Jackson S, Zambrowicz B, Sands AT, Pavel M. Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome. J Clin Oncol. 2017 Jan;35(1):14-23. doi: 10.1200/JCO.2016.69.2780. Epub 2016 Oct 28. PMID: 27918724. 3: Cives M, Strosberg J. Treatment Strategies for Metastatic Neuroendocrine Tumors of the Gastrointestinal Tract. Curr Treat Options Oncol. 2017 Mar;18(3):14. doi: 10.1007/s11864-017-0461-5. PMID: 28286921. 4: Markham A. Telotristat Ethyl: First Global Approval. Drugs. 2017 May;77(7):793-798. doi: 10.1007/s40265-017-0737-x. PMID: 28382568. 5: Choy M. Pharmaceutical Approval Update. P T. 2017 May;42(5):304-305. PMID: 28479837; PMCID: PMC5398621. 6: Kulke MH. Advances in the management of patients with carcinoid syndrome. Clin Adv Hematol Oncol. 2017 Apr;15(4):257-259. PMID: 28591101. 7: Strosberg JR, Halfdanarson TR, Bellizzi AM, Chan JA, Dillon JS, Heaney AP, Kunz PL, O'Dorisio TM, Salem R, Segelov E, Howe JR, Pommier RF, Brendtro K, Bashir MA, Singh S, Soulen MC, Tang L, Zacks JS, Yao JC, Bergsland EK. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors. Pancreas. 2017 Jul;46(6):707-714. doi: 10.1097/MPA.0000000000000850. PMID: 28609356; PMCID: PMC5642985. 8: Telotristat ethyl (Xermelo) for carcinoid syndrome diarrhea. Med Lett Drugs Ther. 2017 Jul 17;59(1525):119-120. PMID: 28699933. 9: Joish VN, Frech F, Lapuerta P. Cost-effectiveness analysis of telotristat ethyl for treatment of carcinoid syndrome diarrhea inadequately controlled with somatostatin analogs. J Med Econ. 2018 Feb;21(2):182-188. doi: 10.1080/13696998.2017.1387120. Epub 2017 Oct 9. PMID: 28959913. 10: Masab M, Saif MW. Telotristat ethyl: proof of principle and the first oral agent in the management of well-differentiated metastatic neuroendocrine tumor and carcinoid syndrome diarrhea. Cancer Chemother Pharmacol. 2017 Dec;80(6):1055-1062. doi: 10.1007/s00280-017-3462-y. Epub 2017 Oct 19. PMID: 29051994. 11: Anthony L, Ervin C, Lapuerta P, Kulke MH, Kunz P, Bergsland E, Hörsch D, Metz DC, Pasieka J, Pavlakis N, Pavel M, Caplin M, Öberg K, Ramage J, Evans E, Yang QM, Jackson S, Arnold K, Law L, DiBenedetti DB. Understanding the Patient Experience with Carcinoid Syndrome: Exit Interviews from a Randomized, Placebo- controlled Study of Telotristat Ethyl. Clin Ther. 2017 Nov;39(11):2158-2168. doi: 10.1016/j.clinthera.2017.09.013. Epub 2017 Oct 23. PMID: 29074312. 12: Joish VN, Frech F, Lapuerta P. Budgetary Impact of Telotristat Ethyl, a Novel Treatment for Patients with Carcinoid Syndrome Diarrhea: A US Health Plan Perspective. Clin Ther. 2017 Dec;39(12):2338-2344. doi: 10.1016/j.clinthera.2017.10.019. Epub 2017 Nov 23. PMID: 29175096. 13: Kasi PM. Telotristat Ethyl for Patients With Carcinoid Syndrome Associated With Chest Pain and Hypertension. Pancreas. 2018 Jan;47(1):e2. doi: 10.1097/MPA.0000000000000971. PMID: 29232344. 14: Pavel M, Gross DJ, Benavent M, Perros P, Srirajaskanthan R, Warner RRP, Kulke MH, Anthony LB, Kunz PL, Hörsch D, Weickert MO, Lapuerta P, Jiang W, Kassler-Taub K, Wason S, Fleming R, Fleming D, Garcia-Carbonero R. Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial. Endocr Relat Cancer. 2018 Mar;25(3):309-322. doi: 10.1530/ERC-17-0455. Epub 2018 Jan 12. PMID: 29330194; PMCID: PMC5811631. 15: Alexandraki KI, Karapanagioti A, Karoumpalis I, Boutzios G, Kaltsas GA. Advances and Current Concepts in the Medical Management of Gastroenteropancreatic Neuroendocrine Neoplasms. Biomed Res Int. 2017;2017:9856140. doi: 10.1155/2017/9856140. Epub 2017 Nov 19. PMID: 29349087; PMCID: PMC5733630. 16: Dillon JS, Chandrasekharan C. Telotristat ethyl: a novel agent for the therapy of carcinoid syndrome diarrhea. Future Oncol. 2018 May;14(12):1155-1164. doi: 10.2217/fon-2017-0340. Epub 2018 Jan 19. PMID: 29350062; PMCID: PMC6734517. 17: Matthes S, Bader M. Peripheral Serotonin Synthesis as a New Drug Target. Trends Pharmacol Sci. 2018 Jun;39(6):560-572. doi: 10.1016/j.tips.2018.03.004. Epub 2018 Apr 5. PMID: 29628275. 18: Weickert MO, Kaltsas G, Hörsch D, Lapuerta P, Pavel M, Valle JW, Caplin ME, Bergsland E, Kunz PL, Anthony LB, Grande E, Öberg K, Welin S, Lombard-Bohas C, Ramage JK, Kittur A, Yang QM, Kulke MH. Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome. Clin Ther. 2018 Jun;40(6):952-962.e2. doi: 10.1016/j.clinthera.2018.04.006. Epub 2018 May 1. PMID: 29724499. 19: Lyseng-Williamson KA. Telotristat Ethyl: A Review in Carcinoid Syndrome Diarrhoea. Drugs. 2018 Jun;78(9):941-950. doi: 10.1007/s40265-018-0935-1. PMID: 29931594. 20: Kasi PM. Telotristat ethyl for the treatment of carcinoid syndrome diarrhea not controlled by somatostatin analogues. Drugs Today (Barc). 2018 Jul;54(7):423-432. doi: 10.1358/dot.2018.54.7.2834460. PMID: 30090879.