Pepstatin A | CAS#26305-03-3 | proteinase inhibitor

MedKoo Cat#: 596731 | Name: Pepstatin A

Description:

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

Pepstatin A, also known as Pepstatin, is a proteinase inhibitor, and a bacterial-derived chemotactic pentapeptide that irreversibly inhibits aspartic proteases, including pepsin, gastricsin, renin, cathepsin E, and cathepsin D. Pepstatin A alters host cell autophagic machinery and leads to a decrease in influenza A virus production. Pepstatin A has been reported to stimulate human neutrophil degranulation.

Chemical Structure

Pepstatin A

CAS#26305-03-3

Theoretical Analysis

MedKoo Cat#: 596731

Name: Pepstatin A

CAS#: 26305-03-3

Chemical Formula: C34H63N5O9

Exact Mass: 685.4626

Molecular Weight: 685.90

Elemental Analysis: C, 59.54; H, 9.26; N, 10.21; O, 20.99

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 1,950.00	2 Weeks
1g	USD 2,950.00	2 Weeks
2g	USD 5,250.00	2 Weeks

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Related CAS #

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Synonym

Pepstatin; NSC 272671; NSC-272671; NSC272671; Pepstatin A; Pepstatina; Pepstatinum;

IUPAC/Chemical Name

(3S,12S,14S,15S,18S)-14-carbamoyl-3,11-dihydroxy-4,12-diisobutyl-18-isopropyl-7,15,22-trimethyl-6,9,17,20-tetraoxo-5,8,13,19-tetraazatricosanoic acid

InChi Key

RYVNEZZFCRDWAU-YOXILXBBSA-N

InChi Code

InChI=1S/C34H63N5O9/c1-17(2)11-23(37-32(33(35)47)21(9)14-27(42)31(20(7)8)39-28(43)13-19(5)6)25(40)15-29(44)36-22(10)34(48)38-24(12-18(3)4)26(41)16-30(45)46/h17-26,31-32,37,40-41H,11-16H2,1-10H3,(H2,35,47)(H,36,44)(H,38,48)(H,39,43)(H,45,46)/t21-,22?,23-,24?,25?,26-,31-,32-/m0/s1

SMILES Code

C[C@@H](CC([C@H](C(C)C)NC(CC(C)C)=O)=O)[C@@H](C(N)=O)N[C@@H](CC(C)C)C(O)CC(NC(C)C(NC([C@@H](O)CC(O)=O)CC(C)C)=O)=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:

Pepstatin (Pepstatin A) is a specific, orally active aspartic protease inhibitor produced by actinomycetes, with IC50s of 4.5 nM, 6.2 nM, 150 nM, 290 nM, 520 nM and 260 nM for hemoglobin-pepsin, hemoglobin-proctase, casein-pepsin, casein-proctase, casein-acid protease and hemoglobin-acid protease, respectively. Pepstatin also inhibits HIV protease.

In vitro activity:

This study demonstrated by site-specific mutagenesis (Asp----Thr) and by pepstatin A inhibition that the recombinant HIV protease is an aspartic-type protease. Furthermore, incubation of HIV-infected H9 cells with pepstatin A inhibited part of the intracellular processing of the HIV gag protein yet had no apparent toxicity on HIV-infected cells during 48 hr of incubation. Reference: Proc Natl Acad Sci U S A. 1988 Sep;85(18):6612-6. https://pubmed.ncbi.nlm.nih.gov/3045820/

In vivo activity:

Pepstatin or ecabet Na, given intragastrically, significantly prevented esophageal lesions, even though they did not affect basal acid secretion in pylorus-ligated rats. Pepstatin significantly inhibited pepsin activity in vivo and in vitro, while ecabet Na inhibited this activity in vitro. These results suggest that pepstatin is highly effective against acid reflux esophagitis, without influencing acid secretion, while L-glutamine aggravated these lesions by increasing the pepsin activity by shifting the intraluminal pH to the optimal pH range for proteolytic action. Reference: Dig Dis Sci. 2006 Feb;51(2):303-9. https://pubmed.ncbi.nlm.nih.gov/16534673/

	Solvent	mg/mL	mM
Solubility
	DMF	3.3	4.81
	DMSO	31.9	46.57

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 685.90 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. Yoshida H, Okamoto K, Iwamoto T, Sakai E, Kanaoka K, Hu JP, Shibata M, Hotokezaka H, Nishishita K, Mizuno A, Kato Y. Pepstatin A, an aspartic proteinase inhibitor, suppresses RANKL-induced osteoclast differentiation. J Biochem. 2006 Mar;139(3):583-90. doi: 10.1093/jb/mvj066. PMID: 16567424. 2. Seelmeier S, Schmidt H, Turk V, von der Helm K. Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6612-6. doi: 10.1073/pnas.85.18.6612. PMID: 3045820; PMCID: PMC282027. 3. Nagahama K, Yamato M, Nishio H, Takeuchi K. Essential role of pepsin in pathogenesis of acid reflux esophagitis in rats. Dig Dis Sci. 2006 Feb;51(2):303-9. doi: 10.1007/s10620-006-3129-8. PMID: 16534673.

In vitro protocol:

In vivo protocol:

1. Nagahama K, Yamato M, Nishio H, Takeuchi K. Essential role of pepsin in pathogenesis of acid reflux esophagitis in rats. Dig Dis Sci. 2006 Feb;51(2):303-9. doi: 10.1007/s10620-006-3129-8. PMID: 16534673.

1: Du C, Wang J, Liu X, Li H, Geng D, Yu L, Chen Y, Zhang J. Construction of Pepstatin A-Conjugated ultrasmall SPIONs for targeted positive MR imaging of epilepsy-overexpressed P-glycoprotein. Biomaterials. 2020 Feb;230:119581. doi: 10.1016/j.biomaterials.2019.119581. Epub 2019 Oct 31. PMID: 31718885. 2: Purushothaman K, Bhat SK, Singh SA, Marathe GK, Appu Rao ARG. Aspartic protease from Aspergillus niger: Molecular characterization and interaction with pepstatin A. Int J Biol Macromol. 2019 Oct 15;139:199-212. doi: 10.1016/j.ijbiomac.2019.07.133. Epub 2019 Jul 30. PMID: 31374272. 3: Rahmani S, Budimir J, Sejalon M, Daurat M, Aggad D, Vivès E, Raehm L, Garcia M, Lichon L, Gary-Bobo M, Durand JO, Charnay C. Large Pore Mesoporous Silica and Organosilica Nanoparticles for Pepstatin A Delivery in Breast Cancer Cells. Molecules. 2019 Jan 17;24(2):332. doi: 10.3390/molecules24020332. PMID: 30658511; PMCID: PMC6359328. 4: Arodola OA, Soliman ME. Hybrid 2D/3D-quantitative structure-activity relationship and modeling studies perspectives of pepstatin A analogs as cathepsin D inhibitors. Future Med Chem. 2018 Jan;10(1):5-26. doi: 10.4155/fmc-2017-0077. Epub 2017 Dec 13. PMID: 29235371. 5: Yu X, Wang J, Liu J, Shen S, Cao Z, Pan J, Zhou S, Pang Z, Geng D, Zhang J. A multimodal Pepstatin A peptide-based nanoagent for the molecular imaging of P-glycoprotein in the brains of epilepsy rats. Biomaterials. 2016 Jan;76:173-86. doi: 10.1016/j.biomaterials.2015.10.050. Epub 2015 Oct 21. PMID: 26524537. 6: Munkhjargal T, AbouLaila M, Terkawi MA, Sivakumar T, Ichikawa M, Davaasuren B, Nyamjargal T, Yokoyama N, Igarashi I. Inhibitory effects of pepstatin A and mefloquine on the growth of Babesia parasites. Am J Trop Med Hyg. 2012 Oct;87(4):681-8. doi: 10.4269/ajtmh.2012.12-0218. Epub 2012 Aug 13. PMID: 22890034; PMCID: PMC3516319. 7: Matúz K, Mótyán J, Li M, Wlodawer A, Tőzsér J. Inhibition of XMRV and HIV-1 proteases by pepstatin A and acetyl-pepstatin. FEBS J. 2012 Sep;279(17):3276-86. doi: 10.1111/j.1742-4658.2012.08714.x. Epub 2012 Aug 17. PMID: 22804908; PMCID: PMC6290463. 8: Aoki W, Kitahara N, Miura N, Morisaka H, Yamamoto Y, Kuroda K, Ueda M. Candida albicans possesses Sap7 as a pepstatin A-insensitive secreted aspartic protease. PLoS One. 2012;7(2):e32513. doi: 10.1371/journal.pone.0032513. Epub 2012 Feb 27. PMID: 22384266; PMCID: PMC3287985. 9: Sangenito LS, Gonçalves KC, Abi-Chacra EA, Sodré CL, d'Avila-Levy CM, Branquinha MH, Santos AL. Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms. Parasitol Res. 2012 Jun;110(6):2533-40. doi: 10.1007/s00436-011-2796-3. Epub 2011 Dec 29. PMID: 22205353. 10: Matarrese P, Nencioni L, Checconi P, Ciarlo L, Gambardella L, Ascione B, Sgarbanti R, Garaci E, Malorni W, Palamara AT. Pepstatin A alters host cell autophagic machinery and leads to a decrease in influenza A virus production. J Cell Physiol. 2011 Dec;226(12):3368-77. doi: 10.1002/jcp.22696. PMID: 21344392. 11: Dostál J, Brynda J, Hrusková-Heidingsfeldová O, Sieglová I, Pichová I, Rezácová P. The crystal structure of the secreted aspartic protease 1 from Candida parapsilosis in complex with pepstatin A. J Struct Biol. 2009 Aug;167(2):145-52. doi: 10.1016/j.jsb.2009.04.004. Epub 2009 May 3. PMID: 19401235. 12: Nascimento AS, Krauchenco S, Golubev AM, Gustchina A, Wlodawer A, Polikarpov I. Statistical coupling analysis of aspartic proteinases based on crystal structures of the Trichoderma reesei enzyme and its complex with pepstatin A. J Mol Biol. 2008 Oct 10;382(3):763-78. doi: 10.1016/j.jmb.2008.07.043. Epub 2008 Jul 22. PMID: 18675276; PMCID: PMC2711637. 13: Zaidi N, Burster T, Sommandas V, Herrmann T, Boehm BO, Driessen C, Voelter W, Kalbacher H. A novel cell penetrating aspartic protease inhibitor blocks processing and presentation of tetanus toxoid more efficiently than pepstatin A. Biochem Biophys Res Commun. 2007 Dec 14;364(2):243-9. doi: 10.1016/j.bbrc.2007.09.114. Epub 2007 Oct 4. PMID: 17937927. 14: Borelli C, Ruge E, Schaller M, Monod M, Korting HC, Huber R, Maskos K. The crystal structure of the secreted aspartic proteinase 3 from Candida albicans and its complex with pepstatin A. Proteins. 2007 Aug 15;68(3):738-48. doi: 10.1002/prot.21425. PMID: 17510964. 15: Consolaro ME, Gasparetto A, Svidzinski TI, Peralta RM. Effect of pepstatin A on the virulence factors of Candida albicans strains isolated from vaginal environment of patients in three different clinical conditions. Mycopathologia. 2006 Aug;162(2):75-82. doi: 10.1007/s11046-006-0026-9. PMID: 16897584. 16: Yoshida H, Okamoto K, Iwamoto T, Sakai E, Kanaoka K, Hu JP, Shibata M, Hotokezaka H, Nishishita K, Mizuno A, Kato Y. Pepstatin A, an aspartic proteinase inhibitor, suppresses RANKL-induced osteoclast differentiation. J Biochem. 2006 Mar;139(3):583-90. doi: 10.1093/jb/mvj066. PMID: 16567424. 17: Binkert C, Frigerio M, Jones A, Meyer S, Pesenti C, Prade L, Viani F, Zanda M. Replacement of isobutyl by trifluoromethyl in pepstatin A selectively affects inhibition of aspartic proteinases. Chembiochem. 2006 Jan;7(1):181-6. doi: 10.1002/cbic.200500180. PMID: 16307463. 18: Petrescu G, Costuleanu M, Slătineanu SM, Costuleanu N, Cernucan DL. Pepstatin A is inducing contractile effects on isolated rat aorta rings. Rev Med Chir Soc Med Nat Iasi. 2002 Oct-Dec;106(4):741-5. PMID: 14974221. 19: Okada M, Irie S, Sawada M, Urae R, Urae A, Iwata N, Ozaki N, Akazawa K, Nakanishi H. Pepstatin A induces extracellular acidification distinct from aspartic protease inhibition in microglial cell lines. Glia. 2003 Aug;43(2):167-74. doi: 10.1002/glia.10237. PMID: 12838508. 20: Takashima T, Kawada N, Maeda N, Okuyama H, Uyama N, Seki S, Arakawa T. Pepstatin A attenuates the inhibitory effect of N-acetyl-L-cysteine on proliferation of hepatic myofibroblasts (stellate cells). Eur J Pharmacol. 2002 Sep 20;451(3):265-70. doi: 10.1016/s0014-2999(02)02296-3. PMID: 12242087.