PF-03882845 | CAS#1023650-66-9 | mineralocorticoid receptor antagonist

MedKoo Cat#: 525939 | Name: PF-03882845

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Description:

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

PF-03882845 is a highly potent (IC50=6.3‐13.4nM,10% fetal bovine serum & IC50= 0.504–1.11 nM, absence of serum) selective orally bioavailable mineralocorticoid receptor antagonist. It prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy.

Chemical Structure

PF-03882845

CAS#1023650-66-9

Theoretical Analysis

MedKoo Cat#: 525939

Name: PF-03882845

CAS#: 1023650-66-9

Chemical Formula: C24H22ClN3O2

Exact Mass: 419.1401

Molecular Weight: 419.91

Elemental Analysis: C, 68.65; H, 5.28; Cl, 8.44; N, 10.01; O, 7.62

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 350.00	Ask
25mg	USD 950.00	Ask

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Related CAS #

No Data

Synonym

PF-03882845; PF 03882845; PF03882845.

IUPAC/Chemical Name

(3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid

InChi Key

XNULRSOGWPFPBL-REWPJTCUSA-N

InChi Code

InChI=1S/C24H22ClN3O2/c25-21-12-18(8-5-17(21)13-26)28-23(14-3-1-2-4-14)20-10-6-15-11-16(24(29)30)7-9-19(15)22(20)27-28/h5,7-9,11-12,14,20,23H,1-4,6,10H2,(H,29,30)/t20-,23-/m0/s1

SMILES Code

O=C(C1=CC=C2C(CC[C@]3([H])[C@H](C4CCCC4)N(C5=CC=C(C#N)C(Cl)=C5)N=C23)=C1)O

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:

PF-3882845 is a remarkably high affinity selective and orally efficacious mineralocorticoid receptor (MR binding IC50=2.7 nM) antagonist

In vitro activity:

TBD

In vivo activity:

Introduction of conformational restriction led to a novel series characterized by exquisite potency and favorable steroid receptor selectivity and pharmacokinetic profile. Oral dosing of 3S,3aR-27d (PF-3882845) in the Dahl salt sensitive preclinical model of salt-induced hypertension and nephropathy showed blood pressure attenuation significantly greater than that with eplerenone, reduction in urinary albumin, and renal protection. As a result of these findings, 3S,3aR-27d was advanced to clinical studies. Reference: J Med Chem. 2010 Aug 26;53(16):5979-6002. https://pubmed.ncbi.nlm.nih.gov/20672822/

Preparing Stock Solutions

The following data is based on the product molecular weight 419.91 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:

Meyers MJ, Arhancet GB, Hockerman SL, Chen X, Long SA, Mahoney MW, Rico JR, Garland DJ, Blinn JR, Collins JT, Yang S, Huang HC, McGee KF, Wendling JM, Dietz JD, Payne MA, Homer BL, Heron MI, Reitz DB, Hu X. Discovery of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy. J Med Chem. 2010 Aug 26;53(16):5979-6002. doi: 10.1021/jm100505n. PMID: 20672822.

In vitro protocol:

TBD

In vivo protocol:

1: Basu S, Mak T, Ulferts R, Wu M, Deegan T, Fujisawa R, Tan KW, Lim CT, Basier C, Canal B, Curran JF, Drury LS, McClure AW, Roberts EL, Weissmann F, Zeisner TU, Beale R, Cowling VH, Howell M, Labib K, Diffley JFX. Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp14 RNA cap methyltransferase. Biochem J. 2021 Jul 16;478(13):2481-2497. doi: 10.1042/BCJ20210219. PMID: 34198328; PMCID: PMC8286817. 2: Bedussi F, Galli D, Fragni M, Valcamonico F, Rossini E, Dalla Volta A, Vezzoli S, Roca E, Ferrari V, Lazzari B, Memo M, Sigala S, Berruti A. Amiloride Is Effective in the Management of Abiraterone-Induced Mineralocorticoid Excess Syndrome without Interfering with Its Antineoplastic Activity. Pharmacology. 2017;100(5-6):261-268. doi: 10.1159/000477547. Epub 2017 Aug 11. PMID: 28797006. 3: Kolkhof P, Nowack C, Eitner F. Nonsteroidal antagonists of the mineralocorticoid receptor. Curr Opin Nephrol Hypertens. 2015 Sep;24(5):417-24. doi: 10.1097/MNH.0000000000000147. PMID: 26083526. 4: Bisping E, Wakula P, Poteser M, Heinzel FR. Targeting cardiac hypertrophy: toward a causal heart failure therapy. J Cardiovasc Pharmacol. 2014 Oct;64(4):293-305. doi: 10.1097/FJC.0000000000000126. PMID: 25286359. 5: Fryer RM, Boustany-Kari CM, MacDonnell SM. Engaging novel cell types, protein targets and efficacy biomarkers in the treatment of diabetic nephropathy. Front Pharmacol. 2014 Aug 7;5:185. doi: 10.3389/fphar.2014.00185. PMID: 25147524; PMCID: PMC4124518. 6: Casimiro-Garcia A, Piotrowski DW, Ambler C, Arhancet GB, Banker ME, Banks T, Boustany-Kari CM, Cai C, Chen X, Eudy R, Hepworth D, Hulford CA, Jennings SM, Loria PM, Meyers MJ, Petersen DN, Raheja NK, Sammons M, She L, Song K, Vrieze D, Wei L. Identification of (R)-6-(1-(4-cyano-3-methylphenyl)-5-cyclopentyl-4,5-dih ydro-1H-pyrazol-3-yl)-2-methoxynicotinic acid, a highly potent and selective nonsteroidal mineralocorticoid receptor antagonist. J Med Chem. 2014 May 22;57(10):4273-88. doi: 10.1021/jm500206r. Epub 2014 Apr 30. PMID: 24738581. 7: Orena S, Maurer TS, She L, Eudy R, Bernardo V, Dash D, Loria P, Banker ME, Tugnait M, Okerberg CV, Qian J, Boustany-Kari CM. PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy. Front Pharmacol. 2013 Oct 14;4:115. doi: 10.3389/fphar.2013.00115. PMID: 24133446; PMCID: PMC3796291. 8: Eudy RJ, Sahasrabudhe V, Sweeney K, Tugnait M, King-Ahmad A, Near K, Loria P, Banker ME, Piotrowski DW, Boustany-Kari CM. The use of plasma aldosterone and urinary sodium to potassium ratio as translatable quantitative biomarkers of mineralocorticoid receptor antagonism. J Transl Med. 2011 Oct 21;9:180. doi: 10.1186/1479-5876-9-180. PMID: 22017794; PMCID: PMC3305907. 9: Meyers MJ, Arhancet GB, Hockerman SL, Chen X, Long SA, Mahoney MW, Rico JR, Garland DJ, Blinn JR, Collins JT, Yang S, Huang HC, McGee KF, Wendling JM, Dietz JD, Payne MA, Homer BL, Heron MI, Reitz DB, Hu X. Discovery of (3S,3aR)-2-(3-chl oro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carbo xylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy. J Med Chem. 2010 Aug 26;53(16):5979-6002. doi: 10.1021/jm100505n. PMID: 20672822.