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MedKoo Cat#: 526021 | Name: PNU-142633
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Description:

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

PNU-142633 selective, high affinity 5-HT1D receptor antagonist and is an experimental drug candidate for the treatment of migraine. PNU-142633 binds with a Ki of 6 nm at the human 5-HT1D receptor and a Ki of> 18 000 nm at the human 5-HT1B receptor.

Chemical Structure

PNU-142633
PNU-142633
CAS#187665-65-2

Theoretical Analysis

MedKoo Cat#: 526021

Name: PNU-142633

CAS#: 187665-65-2

Chemical Formula: C24H30N4O3

Exact Mass: 422.2318

Molecular Weight: 422.53

Elemental Analysis: C, 68.22; H, 7.16; N, 13.26; O, 11.36

Price and Availability

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10mg USD 680.00 2 Weeks
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Synonym
PNU-142633; PNU 142633; PNU142633.
IUPAC/Chemical Name
1H-2-Benzopyran-6-carboxamide, 1-(2-(4-(4-(aminocarbonyl)phenyl)-1-piperazinyl)ethyl)-3,4-dihydro-N-methyl-, (1S)-
InChi Key
PNTVCCRNJOGKGA-QFIPXVFZSA-N
InChi Code
InChI=1S/C24H30N4O3/c1-26-24(30)19-4-7-21-18(16-19)9-15-31-22(21)8-10-27-11-13-28(14-12-27)20-5-2-17(3-6-20)23(25)29/h2-7,16,22H,8-15H2,1H3,(H2,25,29)(H,26,30)/t22-/m0/s1
SMILES Code
O=C(C1=CC=C2C(CCO[C@H]2CCN3CCN(C4=CC=C(C(N)=O)C=C4)CC3)=C1)NC
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
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:
PNU-142633 is a high affinity, selective and orally active 5-HT1D receptor agonist with Kis of 6 nM and > 18 000 nM for human 5-HT1D receptor and human 5-HT1B receptor.
In vitro activity:
PNU-142633 binds with a Ki of 6 nm at the human 5-HT1D receptor and a Ki of> 18 000 nm at the human 5-HT1B receptor. The intrinsic activity of PNU-142633 at the human 5-HT1D receptor was determined to be 70% that of 5-HT in a cytosensor cell-based assay compared with 84% for that of sumatriptan. PNU-142633 was equally effective as sumatriptan and a half-log more potent than sumatriptan in preventing plasma protein extravasation induced by electrical stimulation of the trigeminal ganglion. Like sumatriptan, PNU-142633 reduced the increase in cat nucleus trigeminal caudalis blood flow elicited by electrical stimulation of the trigeminal ganglion compared with the vehicle control. The direct vasoconstrictor potential of PNU-142633 was evaluated in vascular beds. Reference: Cephalalgia. 2002 Dec;22(10):799-806. https://pubmed.ncbi.nlm.nih.gov/12485205/
In vivo activity:
Rizatriptan did not reverse the dural dilation evoked by CGRP indicating an action on presynaptic receptors located on trigeminal sensory fibres innervating dural blood vessels. In addition, neurogenic dural vasodilation was also blocked by the selective 5-HT(1D) agonist PNU-142633 (100 microg kg(-1)) but not by the 5-HT(1F) agonist LY334370 (3 mg kg(-1)) suggesting that rizatriptan blocks neurogenic vasodilation via an action on 5-HT(1D) receptors located on perivascular trigeminal nerves to inhibit CGRP release. Reference: Br J Pharmacol. 2001 Aug;133(7):1029-34. https://pubmed.ncbi.nlm.nih.gov/11487512/
Solvent mg/mL mM comments
Solubility
DMSO 42.3 100.00
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 422.53 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.

Recalculate based on batch purity %
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. McCall RB, Huff R, Chio CL, TenBrink R, Bergh CL, Ennis MD, Ghazal NB, Hoffman RL, Meisheri K, Higdon NR, Hall E. Preclinical studies characterizing the anti-migraine and cardiovascular effects of the selective 5-HT1D receptor agonist PNU-142633. Cephalalgia. 2002 Dec;22(10):799-806. doi: 10.1046/j.1468-2982.2002.00459.x. PMID: 12485205. 2. Williamson DJ, Hill RG, Shepheard SL, Hargreaves RJ. The anti-migraine 5-HT(1B/1D) agonist rizatriptan inhibits neurogenic dural vasodilation in anaesthetized guinea-pigs. Br J Pharmacol. 2001 Aug;133(7):1029-34. doi: 10.1038/sj.bjp.0704162. PMID: 11487512; PMCID: PMC1572868.
In vitro protocol:
1. McCall RB, Huff R, Chio CL, TenBrink R, Bergh CL, Ennis MD, Ghazal NB, Hoffman RL, Meisheri K, Higdon NR, Hall E. Preclinical studies characterizing the anti-migraine and cardiovascular effects of the selective 5-HT1D receptor agonist PNU-142633. Cephalalgia. 2002 Dec;22(10):799-806. doi: 10.1046/j.1468-2982.2002.00459.x. PMID: 12485205.
In vivo protocol:
1. Williamson DJ, Hill RG, Shepheard SL, Hargreaves RJ. The anti-migraine 5-HT(1B/1D) agonist rizatriptan inhibits neurogenic dural vasodilation in anaesthetized guinea-pigs. Br J Pharmacol. 2001 Aug;133(7):1029-34. doi: 10.1038/sj.bjp.0704162. PMID: 11487512; PMCID: PMC1572868.
1: García-Pedraza JÁ, Hernández-Abreu O, Morán A, Carretero J, García-Domingo M, Villalón CM. Role of peripheral 5-HT5A receptors in 5-HT-induced cardiac sympatho-inhibition in type 1 diabetic rats. Sci Rep. 2020 Nov 9;10(1):19358. doi: 10.1038/s41598-020-76298-6. PMID: 33168874; PMCID: PMC7652863. 2: García-Pedraza JÁ, Hernández-Abreu O, García M, Morán A, Villalón CM. Chronic 5-HT2 receptor blockade unmasks the role of 5-HT1F receptors in the inhibition of rat cardioaccelerator sympathetic outflow. Can J Physiol Pharmacol. 2018 Apr;96(4):328-336. doi: 10.1139/cjpp-2017-0191. Epub 2017 Sep 8. PMID: 28886249. 3: Barbanti P, Aurilia C, Egeo G, Fofi L, Palmirotta R. Serotonin receptor targeted therapy for migraine treatment: an overview of drugs in phase I and II clinical development. Expert Opin Investig Drugs. 2017 Mar;26(3):269-277. doi: 10.1080/13543784.2017.1283404. Epub 2017 Feb 1. PMID: 28103158. 4: Amrutkar DV, Ploug KB, Hay-Schmidt A, Porreca F, Olesen J, Jansen-Olesen I. mRNA expression of 5-hydroxytryptamine 1B, 1D, and 1F receptors and their role in controlling the release of calcitonin gene-related peptide in the rat trigeminovascular system. Pain. 2012 Apr;153(4):830-838. doi: 10.1016/j.pain.2012.01.005. Epub 2012 Feb 4. PMID: 22305629. 5: González-Hernández A, Manrique-Maldonado G, Lozano-Cuenca J, Muñoz-Islas E, Centurión D, Maassen VanDenBrink A, Villalón CM. The 5-HT(1) receptors inhibiting the rat vasodepressor sensory CGRPergic outflow: further involvement of 5-HT(1F), but not 5-HT(1A) or 5-HT(1D), subtypes. Eur J Pharmacol. 2011 Jun 1;659(2-3):233-43. doi: 10.1016/j.ejphar.2011.03.035. Epub 2011 Apr 4. PMID: 21473863. 6: Muñoz-Islas E, Lozano-Cuenca J, González-Hernández A, Ramírez-Rosas MB, Sánchez-López A, Centurión D, Maassenvandenbrink A, Villalón CM. Spinal sumatriptan inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors. Eur J Pharmacol. 2009 Aug 1;615(1-3):133-8. doi: 10.1016/j.ejphar.2009.04.070. Epub 2009 May 19. PMID: 19460365. 7: Muñoz-Islas E, Gupta S, Jiménez-Mena LR, Lozano-Cuenca J, Sánchez-López A, Centurión D, Mehrotra S, MaassenVanDenBrink A, Villalón CM. Donitriptan, but not sumatriptan, inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors. Br J Pharmacol. 2006 Sep;149(1):82-91. doi: 10.1038/sj.bjp.0706839. Epub 2006 Jul 31. PMID: 16880765; PMCID: PMC1629409. 8: Villalón CM, Centurión D, Valdivia LF, de Vries P, Saxena PR. Migraine: pathophysiology, pharmacology, treatment and future trends. Curr Vasc Pharmacol. 2003 Mar;1(1):71-84. doi: 10.2174/1570161033386826. PMID: 15320857. 9: Sánchez-López A, Centurión D, Vázquez E, Arulmani U, Saxena PR, Villalón CM. Further characterization of the 5-HT1 receptors mediating cardiac sympatho- inhibition in pithed rats: pharmacological correlation with the 5-HT1B and 5-HT1D subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb;369(2):220-7. doi: 10.1007/s00210-003-0842-0. Epub 2003 Dec 12. PMID: 14673512. 10: Sánchez-Lopez A, Centurión D, Vázquez E, Arulmani U, Saxena PR, Villalón CM. Pharmacological profile of the 5-HT-induced inhibition of cardioaccelerator sympathetic outflow in pithed rats: correlation with 5-HT1 and putative 5-ht5A/5B receptors. Br J Pharmacol. 2003 Oct;140(4):725-35. doi: 10.1038/sj.bjp.0705489. Epub 2003 Sep 22. PMID: 14504136; PMCID: PMC1574076. 11: McCall RB, Huff R, Chio CL, TenBrink R, Bergh CL, Ennis MD, Ghazal NB, Hoffman RL, Meisheri K, Higdon NR, Hall E. Preclinical studies characterizing the anti-migraine and cardiovascular effects of the selective 5-HT1D receptor agonist PNU-142633. Cephalalgia. 2002 Dec;22(10):799-806. doi: 10.1046/j.1468-2982.2002.00459.x. PMID: 12485205. 12: Villalón CM, Centurión D, Valdivia LF, De Vries P, Saxena PR. An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210. PMID: 12434581. 13: Ferrari MD. Re: Gomez-Mancilla et al. Safety and efficacy of PNU-142633, a selective 5-HT(1D) agonist, in patients with acute migraine. Cephalalgia 2001;21:727-32. Cephalalgia. 2001 Sep;21(7):711. doi: 10.1046/j.0333-1024.2001.00267.x. PMID: 11603382. 14: Gomez-Mancilla B, Cutler NR, Leibowitz MT, Spierings EL, Klapper JA, Diamond S, Goldstein J, Smith T, Couch JR, Fleishaker J, Azie N, Blunt DE. Safety and efficacy of PNU-142633, a selective 5-HT1D agonist, in patients with acute migraine. Cephalalgia. 2001 Sep;21(7):727-32. doi: 10.1046/j.1468-2982.2001.00208.x. PMID: 11595000. 15: Williamson DJ, Hill RG, Shepheard SL, Hargreaves RJ. The anti-migraine 5-HT(1B/1D) agonist rizatriptan inhibits neurogenic dural vasodilation in anaesthetized guinea-pigs. Br J Pharmacol. 2001 Aug;133(7):1029-34. doi: 10.1038/sj.bjp.0704162. PMID: 11487512; PMCID: PMC1572868. 16: Centurión D, Sánchez-López A, De Vries P, Saxena PR, Villalón CM. The GR127935-sensitive 5-HT(1) receptors mediating canine internal carotid vasoconstriction: resemblance to the 5-HT(1B), but not to the 5-HT(1D) or 5-ht(1F), receptor subtype. Br J Pharmacol. 2001 Mar;132(5):991-8. doi: 10.1038/sj.bjp.0703913. PMID: 11226129; PMCID: PMC1572652. 17: Villalón CM, Sánchez-López A, Centurión D, Saxena PR. Unravelling the pharmacological profile of the canine external carotid vasodilator '5-HT1-like' receptors: coexistence of sympatho-inhibitory 5-HT1B and postjunctional 5-HT7 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2001 Jan;363(1):73-80. doi: 10.1007/s002100000333. PMID: 11191839. 18: Fleishaker JC, Pearson LK, Knuth DW, Gomez-Mancilla B, Francom SF, McIntosh MJ, Freestone S, Azie NE. Pharmacokinetics and tolerability of a novel 5-HT1D agonist, PNU-142633F. Int J Clin Pharmacol Ther. 1999 Oct;37(10):487-92. PMID: 10543315.