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MedKoo Cat#: 522485 | Name: PF-5190457
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Description:

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

PF-5190457 is an orally available, potent and selective ghrelin receptor inverse agonist. PF-5190457 potently increases insulin secretion in glucose-stimulated human islets. PF-5190457 has a superior balance of ghrelin receptor pharmacology and off-target selectivity. On the basis of its promising pharmacological and safety profile, PF-5190457 was advanced to human clinical trials.

Chemical Structure

PF-5190457
PF-5190457
CAS# 1334782-79-4

Theoretical Analysis

MedKoo Cat#: 522485

Name: PF-5190457

CAS#: 1334782-79-4

Chemical Formula: C29H32N6OS

Exact Mass: 512.2358

Molecular Weight: 512.68

Elemental Analysis: C, 67.94; H, 6.29; N, 16.39; O, 3.12; S, 6.25

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
25mg USD 1,250.00 2 Weeks
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Related CAS #
No Data
Synonym
PF-5190457; PF 5190457; PF5190457; PF-05190457; PF05190457; PF 05190457.
IUPAC/Chemical Name
(R)-2-(2-methylimidazo[2,1-b]thiazol-6-yl)-1-(2-(5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonan-7-yl)ethan-1-one
InChi Key
ZIUDADZJCKGWKR-AREMUKBSSA-N
InChi Code
InChI=1S/C29H32N6OS/c1-19-11-25(31-18-30-19)22-3-5-24-21(12-22)4-6-26(24)35-16-29(17-35)7-9-33(10-8-29)27(36)13-23-15-34-14-20(2)37-28(34)32-23/h3,5,11-12,14-15,18,26H,4,6-10,13,16-17H2,1-2H3/t26-/m1/s1
SMILES Code
CC1=CC(C2=CC3=C([C@H](N4CC5(CCN(C(CC(N=C6S7)=CN6C=C7C)=O)CC5)C4)CC3)C=C2)=NC=N1
Appearance
Solid powder
Purity
>95% (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, not in 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

Preparing Stock Solutions

The following data is based on the product molecular weight 512.68 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
1: Lékó AH, Gregory-Flores A, Marchette RCN, Gomez JL, Vendruscolo JCM, Repunte- Canonigo V, Choung V, Deschaine SL, Whiting KE, Jackson SN, Cornejo MP, Perello M, You ZB, Eckhaus M, Rasineni K, Janda KD, Zorman B, Sumazin P, Koob GF, Michaelides M, Sanna PP, Vendruscolo LF, Leggio L. Genetic or pharmacological GHSR blockade has sexually dimorphic effects in rodents on a high-fat diet. Commun Biol. 2024 May 25;7(1):632. doi: 10.1038/s42003-024-06303-5. PMID: 38796563; PMCID: PMC11127961. 2: Leggio L, Leko A, Gregory-Flores A, Marchette R, Gomez J, Vendruscolo J, Repunte-Canonigo V, Chuong V, Deschaine S, Whiting K, Jackson S, Cornejo M, Perello M, You ZB, Eckhaus M, Janda K, Zorman B, Sumazin P, Koob G, Michaelides M, Sanna PP, Vendruscolo L. Genetic or pharmacological GHSR blockade has sexually dimorphic effects in rodents on a high-fat diet. Res Sq [Preprint]. 2023 Oct 18:rs.3.rs-3236045. doi: 10.21203/rs.3.rs-3236045/v1. Update in: Commun Biol. 2024 May 25;7(1):632. doi: 10.1038/s42003-024-06303-5. PMID: 37886546; PMCID: PMC10602167. 3: Richardson RS, Sulima A, Rice KC, Kucharczk JA, Janda KD, Nisbett KE, Koob GF, Vendruscolo LF, Leggio L. Pharmacological GHSR (ghrelin receptor) blockade reduces alcohol binge-like drinking in male and female mice. Neuropharmacology. 2023 Nov 1;238:109643. doi: 10.1016/j.neuropharm.2023.109643. Epub 2023 Jun 25. PMID: 37369277; PMCID: PMC10513123. 4: Deschaine SL, Hedegaard MA, Pince CL, Farokhnia M, Moose JE, Stock IA, Adusumalli S, Akhlaghi F, Hougland JL, Sulima A, Rice KC, Koob GF, Vendruscolo LF, Holst B, Leggio L. Initial Pharmacological Characterization of a Major Hydroxy Metabolite of PF-5190457: Inverse Agonist Activity of PF-6870961 at the Ghrelin Receptor. J Pharmacol Exp Ther. 2023 Aug;386(2):117-128. doi: 10.1124/jpet.122.001393. Epub 2023 Jan 11. PMID: 36631279; PMCID: PMC10353127. 5: Burnette EM, Nieto SJ, Grodin EN, Meredith LR, Hurley B, Miotto K, Gillis AJ, Ray LA. Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. Drugs. 2022 Feb;82(3):251-274. doi: 10.1007/s40265-021-01670-3. Epub 2022 Feb 8. PMID: 35133639; PMCID: PMC8888464. 6: Sulima A, Akhlaghi F, Leggio L, Rice KC. Synthesis of PF-6870961, a major hydroxy metabolite of the novel ghrelin receptor inverse agonist PF-5190457. Bioorg Med Chem. 2021 Nov 15;50:116465. doi: 10.1016/j.bmc.2021.116465. Epub 2021 Oct 12. PMID: 34662828; PMCID: PMC9837661. 7: Cobbina E, Lee MR, Leggio L, Akhlaghi F. A Population Pharmacokinetic Analysis of PF-5190457, a Novel Ghrelin Receptor Inverse Agonist in Healthy Volunteers and in Heavy Alcohol Drinkers. Clin Pharmacokinet. 2021 Apr;60(4):471-484. doi: 10.1007/s40262-020-00942-7. Epub 2020 Nov 5. PMID: 33155163; PMCID: PMC8855888. 8: Farokhnia M, Portelli J, Lee MR, McDiarmid GR, Munjal V, Abshire KM, Battista JT, Browning BD, Deschaine SL, Akhlaghi F, Leggio L. Effects of exogenous ghrelin administration and ghrelin receptor blockade, in combination with alcohol, on peripheral inflammatory markers in heavy-drinking individuals: Results from two human laboratory studies. Brain Res. 2020 Aug 1;1740:146851. doi: 10.1016/j.brainres.2020.146851. Epub 2020 Apr 24. PMID: 32339499; PMCID: PMC8715722. 9: Adusumalli S, Jamwal R, Leggio L, Akhlaghi F. Development and validation of an assay for a novel ghrelin receptor inverse agonist PF-5190457 and its major hydroxy metabolite (PF-6870961) by LC-MS/MS in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Nov 1;1130-1131:121820. doi: 10.1016/j.jchromb.2019.121820. Epub 2019 Oct 8. PMID: 31670107. 10: Lee MR, Farokhnia M, Cobbina E, Saravanakumar A, Li X, Battista JT, Farinelli LA, Akhlaghi F, Leggio L. Endocrine effects of the novel ghrelin receptor inverse agonist PF-5190457: Results from a placebo-controlled human laboratory alcohol co-administration study in heavy drinkers. Neuropharmacology. 2020 Jun 15;170:107788. doi: 10.1016/j.neuropharm.2019.107788. Epub 2019 Sep 23. PMID: 31557492; PMCID: PMC7085971. 11: Adusumalli S, Jamwal R, Obach RS, Ryder TF, Leggio L, Akhlaghi F. Role of Molybdenum-Containing Enzymes in the Biotransformation of the Novel Ghrelin Receptor Inverse Agonist PF-5190457: A Reverse Translational Bed-to-Bench Approach. Drug Metab Dispos. 2019 Aug;47(8):874-882. doi: 10.1124/dmd.119.087015. Epub 2019 Jun 10. PMID: 31182423; PMCID: PMC6636241. 12: Farokhnia M, Faulkner ML, Piacentino D, Lee MR, Leggio L. Ghrelin: From a gut hormone to a potential therapeutic target for alcohol use disorder. Physiol Behav. 2019 May 15;204:49-57. doi: 10.1016/j.physbeh.2019.02.008. Epub 2019 Feb 7. PMID: 30738971. 13: Farokhnia M, Lee MR, Farinelli LA, Ramchandani VA, Akhlaghi F, Leggio L. Pharmacological manipulation of the ghrelin system and alcohol hangover symptoms in heavy drinking individuals: Is there a link? Pharmacol Biochem Behav. 2018 Sep;172:39-49. doi: 10.1016/j.pbb.2018.07.004. Epub 2018 Jul 17. PMID: 30030128. 14: Lee MR, Tapocik JD, Ghareeb M, Schwandt ML, Dias AA, Le AN, Cobbina E, Farinelli LA, Bouhlal S, Farokhnia M, Heilig M, Akhlaghi F, Leggio L. The novel ghrelin receptor inverse agonist PF-5190457 administered with alcohol: preclinical safety experiments and a phase 1b human laboratory study. Mol Psychiatry. 2020 Feb;25(2):461-475. doi: 10.1038/s41380-018-0064-y. Epub 2018 May 4. PMID: 29728704; PMCID: PMC6215751. 15: Denney WS, Sonnenberg GE, Carvajal-Gonzalez S, Tuthill T, Jackson VM. Pharmacokinetics and pharmacodynamics of PF-05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects. Br J Clin Pharmacol. 2017 Feb;83(2):326-338. doi: 10.1111/bcp.13127. Epub 2016 Oct 29. PMID: 27621150; PMCID: PMC5237700. 16: Kong J, Chuddy J, Stock IA, Loria PM, Straub SV, Vage C, Cameron KO, Bhattacharya SK, Lapham K, McClure KF, Zhang Y, Jackson VM. Pharmacological characterization of the first in class clinical candidate PF-05190457: a selective ghrelin receptor competitive antagonist with inverse agonism that increases vagal afferent firing and glucose-dependent insulin secretion ex vivo. Br J Pharmacol. 2016 May;173(9):1452-64. doi: 10.1111/bph.13439. Epub 2016 Mar 17. PMID: 26784385; PMCID: PMC4831304. 17: Ghareeb M, Leggio L, El-Kattan A, Akhlaghi F. Development and validation of an UPLC-MS/MS assay for quantitative analysis of the ghrelin receptor inverse agonist PF-5190457 in human or rat plasma and rat brain. Anal Bioanal Chem. 2015 Jul;407(19):5603-13. doi: 10.1007/s00216-015-8730-2. Epub 2015 May 7. PMID: 25943263; PMCID: PMC4499019. 18: Bhattacharya SK, Andrews K, Beveridge R, Cameron KO, Chen C, Dunn M, Fernando D, Gao H, Hepworth D, Jackson VM, Khot V, Kong J, Kosa RE, Lapham K, Loria PM, Londregan AT, McClure KF, Orr ST, Patel J, Rose C, Saenz J, Stock IA, Storer G, VanVolkenburg M, Vrieze D, Wang G, Xiao J, Zhang Y. Discovery of PF-5190457, a Potent, Selective, and Orally Bioavailable Ghrelin Receptor Inverse Agonist Clinical Candidate. ACS Med Chem Lett. 2014 Feb 24;5(5):474-9. doi: 10.1021/ml400473x. PMID: 24900864; PMCID: PMC4027753.