PRX-08066 free base | CAS#866206-54-4 | 5-hydroxytryptamine receptor 2B antagonist

MedKoo Cat#: 526697 | Name: PRX-08066 free base

Description:

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

PRX-08066 is a a novel 5-hydroxytryptamine receptor 2B antagonist, reduces monocrotaline-induced pulmonary arterial hypertension (PAH) and right ventricular hypertrophy in rats.

Chemical Structure

PRX-08066 free base

CAS#866206-54-4

Theoretical Analysis

MedKoo Cat#: 526697

Name: PRX-08066 free base

CAS#: 866206-54-4

Chemical Formula: C19H17ClFN5S

Exact Mass: 401.0877

Molecular Weight: 401.89

Elemental Analysis: C, 56.78; H, 4.26; Cl, 8.82; F, 4.73; N, 17.43; S, 7.98

Price and Availability

Size	Price	Availability
100mg	USD 950.00	2 Weeks
200mg	USD 1,650.00	2 Weeks
500mg	USD 3,650.00	2 Weeks
1g	USD 5,450.00	2 Weeks

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Related CAS #

866206-55-5(PRX-08066 Maleate)

Synonym

PRX-08066; PRX 08066; PRX08066.

IUPAC/Chemical Name

5-((4-(6-Chlorothieno(2,3-d)pyrimidine-4-ylamino)piperidin-1-yl)methyl)-2-fluorobenzonitrile

InChi Key

RPYIKXHIQXRXEM-BTJKTKAUSA-N

InChi Code

InChI=1S/C19H17ClFN5S.C4H4O4/c20-17-8-15-18(23-11-24-19(15)27-17)25-14-3-5-26(6-4-14)10-12-1-2-16(21)13(7-12)9-22;5-3(6)1-2-4(7)8/h1-2,7-8,11,14H,3-6,10H2,(H,23,24,25);1-2H,(H,5,6)(H,7,8)/b;2-1-

SMILES Code

N#CC1=CC(CN2CCC(NC3=C(C=C(Cl)S4)C4=NC=N3)CC2)=CC=C1F

Appearance

Solid powder

Purity

>98% (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, ethanol, and water

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

In the 5-HT(2B) expressing SI-NET cell line, KRJ-I, PRX-08066 inhibited proliferation (IC(50) 4.6 x 10(-9)M) and 5-HT secretion (6.9 x 10(-9)M) and decreased ERK1/2 phosphorylation and profibrotic growth factor synthesis and secretion (transforming growth factor beta 1 [TGFbeta1], connective tissue growth factor [CTGF] and fibroblast growth factor [FGF2]).

In vitro activity:

PRX-08066 demonstrated promising effects in the context of small intestinal neuroendocrine tumors (SI-NETs). and PRX-08066 showed the ability to inhibit both tumor cell proliferation and the secretion of 5-HT. In the cell line KRJ-I, PRX-08066 inhibited cell growth and 5-HT release and reduced the activation of signaling pathways involved in fibrosis and the synthesis of fibrotic growth factors such as TGFbeta1, CTGF, and FGF2. Reference: Cancer. 2010 Jun 15;116(12):2902-12. https://pubmed.ncbi.nlm.nih.gov/20564397/

In vivo activity:

In a PAH rat model, PAH rats were administered PRX-08066 orally for five weeks. The results revealed significant improvements in right ventricular ejection fraction, reduced peak pulmonary artery pressure, reduced pulmonary arteriole wall thickening and lumen occlusion, and decreased right ventricle size compared to the MCT control group. Reference: J Pharmacol Exp Ther. 2010 Aug;334(2):364-72. https://pubmed.ncbi.nlm.nih.gov/20430844/

	Solvent	mg/mL	mM
Solubility
	DMSO	96.0	238.87
	Ethanol	91.0	226.43
	Water	95.0	236.38

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 401.89 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. Svejda B, Kidd M, Giovinazzo F, Eltawil K, Gustafsson BI, Pfragner R, Modlin IM. The 5-HT(2B) receptor plays a key regulatory role in both neuroendocrine tumor cell proliferation and the modulation of the fibroblast component of the neoplastic microenvironment. Cancer. 2010 Jun 15;116(12):2902-12. doi: 10.1002/cncr.25049. PMID: 20564397. 2. Porvasnik SL, Germain S, Embury J, Gannon KS, Jacques V, Murray J, Byrne BJ, Shacham S, Al-Mousily F. PRX-08066, a novel 5-hydroxytryptamine receptor 2B antagonist, reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats. J Pharmacol Exp Ther. 2010 Aug;334(2):364-72. doi: 10.1124/jpet.109.165001. Epub 2010 Apr 29. PMID: 20430844.

In vitro protocol:

In vivo protocol:

1. Porvasnik SL, Germain S, Embury J, Gannon KS, Jacques V, Murray J, Byrne BJ, Shacham S, Al-Mousily F. PRX-08066, a novel 5-hydroxytryptamine receptor 2B antagonist, reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats. J Pharmacol Exp Ther. 2010 Aug;334(2):364-72. doi: 10.1124/jpet.109.165001. Epub 2010 Apr 29. PMID: 20430844.

1: Lin S, Wang L, Han C, Dai Y, Li C, Liu Y, Zhang B, Huang N, Zhang A, Zhang T, Wang Y, Xie J, Tang H, Cheng Y, Yao H, Lou M, Xue L, Wu ZB. Targeting HTR2B suppresses non-functioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis. Neuro Oncol. 2024 Jul 11:noae130. doi: 10.1093/neuonc/noae130. Epub ahead of print. PMID: 38989697. 2: Weidmann C, Bérubé J, Piquet L, de la Fouchardière A, Landreville S. Expression of the serotonin receptor 2B in uveal melanoma and effects of an antagonist on cell lines. Clin Exp Metastasis. 2018 Mar;35(3):123-134. doi: 10.1007/s10585-018-9894-x. Epub 2018 Apr 25. PMID: 29696577. 3: Löfdahl A, Wenglén C, Rydell-Törmänen K, Westergren-Thorsson G, Larsson- Callerfelt AK. Effects of 5-Hydroxytryptamine Class 2 Receptor Antagonists on Bronchoconstriction and Pulmonary Remodeling Processes. Am J Pathol. 2018 May;188(5):1113-1119. doi: 10.1016/j.ajpath.2018.01.006. Epub 2018 Feb 16. PMID: 29454752. 4: Kim SK, Li Y, Abrol R, Heo J, Goddard WA 3rd. Predicted structures and dynamics for agonists and antagonists bound to serotonin 5-HT2B and 5-HT2C receptors. J Chem Inf Model. 2011 Feb 28;51(2):420-33. doi: 10.1021/ci100375b. Epub 2011 Feb 7. PMID: 21299232; PMCID: PMC3070210. 5: Svejda B, Kidd M, Giovinazzo F, Eltawil K, Gustafsson BI, Pfragner R, Modlin IM. The 5-HT(2B) receptor plays a key regulatory role in both neuroendocrine tumor cell proliferation and the modulation of the fibroblast component of the neoplastic microenvironment. Cancer. 2010 Jun 15;116(12):2902-12. doi: 10.1002/cncr.25049. PMID: 20564397. 6: Porvasnik SL, Germain S, Embury J, Gannon KS, Jacques V, Murray J, Byrne BJ, Shacham S, Al-Mousily F. PRX-08066, a novel 5-hydroxytryptamine receptor 2B antagonist, reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats. J Pharmacol Exp Ther. 2010 Aug;334(2):364-72. doi: 10.1124/jpet.109.165001. Epub 2010 Apr 29. PMID: 20430844. 7: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Sep;30(7):543-88. PMID: 18985183.