PACMA 31 | CAS#1401089-31-3 | PDI inhibitor

MedKoo Cat#: 531394 | Name: PACMA 31

Featured

Description:

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

PACMA 31 is an orally bioavailable, selective inhibitor (IC50 = 10 μM) of protein disulfide isomerase (PDI), an endoplasmic reticulum protein that regulates oxidative protein folding by catalyzing the breakage and reformation of disulfide bonds. PDI is upregulated in ovarian, and several other cancers. PACMA 31 dose dependently inhibits proliferation of OVCAR-8 in culture and in a tumor xenograft model.

Chemical Structure

PACMA 31

CAS#1401089-31-3

Theoretical Analysis

MedKoo Cat#: 531394

Name: PACMA 31

CAS#: 1401089-31-3

Chemical Formula: C21H22N2O6S

Exact Mass: 430.1199

Molecular Weight: 430.48

Elemental Analysis: C, 58.59; H, 5.15; N, 6.51; O, 22.30; S, 7.45

Price and Availability

Size	Price	Availability
5mg	USD 350.00	2 Weeks
10mg	USD 550.00	2 Weeks
25mg	USD 950.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

PACMA 31; PACMA31; PACMA-31;

IUPAC/Chemical Name

N-(2,4-Dimethoxyphenyl)-N-(1-oxo-2-propyn-1-yl)-2-(2-thienyl)glycyl-glycine ethyl ester

InChi Key

AHOOZADJPNUFOQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H22N2O6S/c1-5-18(24)23(15-10-9-14(27-3)12-16(15)28-4)20(17-8-7-11-30-17)21(26)22-13-19(25)29-6-2/h1,7-12,20H,6,13H2,2-4H3,(H,22,26)

SMILES Code

O=C(OCC)CNC(C(C1=CC=CS1)N(C2=CC=C(OC)C=C2OC)C(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

>3 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:

PACMA 31 is an irreversible, orally active protein disulfide isomerase (PDI) inhibitor with an IC50 of 10 μM.

In vitro activity:

Results reveal that PACMA 31 selectively inhibits TrxR over the related glutathione reductase (GR) and in the presence of reduced glutathione (GSH). Further studies with mutant enzyme and molecular docking suggest that the propynamide fragment of PACMA 31 interacts covalently with the selenocysteine residue of TrxR. Moreover, PACMA 31 effectively and selectively curbs TrxR activity in cells and further stimulates the production of reactive oxygen species (ROS) at low micromolar concentrations, which in turn triggers the accumulation of oxidized thioredoxin (Trx) and GSSG in cells. Follow-up studies demonstrate that PACMA 31 targets TrxR in cells to induce oxidative stress-mediated cancer cell apoptosis. Reference: Biochim Biophys Acta Mol Cell Res. 2022 Oct;1869(10):119323. https://pubmed.ncbi.nlm.nih.gov/35793738/

In vivo activity:

The effects of PDI blockade in vivo were examined by treating mice with the irreversible PDI inhibitor, PACMA-31, in an ovalbumin-induced model of food allergy. Insulin turbidimetric assays demonstrated that curcumin is a potent PDI inhibitor and pre-treatment of mast cells with curcumin or established PDI inhibitors such as bacitracin, rutin or PACMA-31, resulted in the suppression of IgE-mediated activation and the secretion of various cytokines. This was accompanied by decreased mast cell proliferation, FcεRI expression, and mast cell degranulation. Similarly, treatment of allergic BALB/c mice with PACMA-31 attenuated the development of food allergy resulting in decreased allergic diarrhea, mast cell activation, and fewer intestinal mast cell. Reference: Front Immunol. 2020 Dec 22;11:606837. https://pubmed.ncbi.nlm.nih.gov/33414789/

	Solvent	mg/mL	mM
Solubility
	DMSO	71.5	166.15

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 430.48 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. Xu Q, Zhang J, Zhao Z, Chu Y, Fang J. Revealing PACMA 31 as a new chemical type TrxR inhibitor to promote cancer cell apoptosis. Biochim Biophys Acta Mol Cell Res. 2022 Oct;1869(10):119323. doi: 10.1016/j.bbamcr.2022.119323. Epub 2022 Jul 4. PMID: 35793738. 2. Xu S, Butkevich AN, Yamada R, Zhou Y, Debnath B, Duncan R, Zandi E, Petasis NA, Neamati N. Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16348-53. doi: 10.1073/pnas.1205226109. Epub 2012 Sep 17. PMID: 22988091; PMCID: PMC3479552. 3. Krajewski D, Polukort SH, Gelzinis J, Rovatti J, Kaczenski E, Galinski C, Pantos M, Shah NN, Schneider SS, Kennedy DR, Mathias CB. Protein Disulfide Isomerases Regulate IgE-Mediated Mast Cell Responses and Their Inhibition Confers Protective Effects During Food Allergy. Front Immunol. 2020 Dec 22;11:606837. doi: 10.3389/fimmu.2020.606837. PMID: 33414789; PMCID: PMC7783394.

In vitro protocol:

In vivo protocol:

1. Krajewski D, Polukort SH, Gelzinis J, Rovatti J, Kaczenski E, Galinski C, Pantos M, Shah NN, Schneider SS, Kennedy DR, Mathias CB. Protein Disulfide Isomerases Regulate IgE-Mediated Mast Cell Responses and Their Inhibition Confers Protective Effects During Food Allergy. Front Immunol. 2020 Dec 22;11:606837. doi: 10.3389/fimmu.2020.606837. PMID: 33414789; PMCID: PMC7783394. 2. Xu S, Butkevich AN, Yamada R, Zhou Y, Debnath B, Duncan R, Zandi E, Petasis NA, Neamati N. Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16348-53. doi: 10.1073/pnas.1205226109. Epub 2012 Sep 17. PMID: 22988091; PMCID: PMC3479552.

1: Oh M, Jang SY, Lee JY, Kim JW, Jung Y, Kim J, Seo J, Han TS, Jang E, Son HY, Kim D, Kim MW, Park JS, Song KH, Oh KJ, Kim WK, Bae KH, Huh YM, Kim SH, Kim D, Han BS, Lee SC, Hwang GS, Lee EW. The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism. Nat Commun. 2023 Sep 15;14(1):5728. doi: 10.1038/s41467-023-41462-9. PMID: 37714840; PMCID: PMC10504358. 2: Beckmann L, Mäder J, Voigtlaender M, Klingler F, Schulenkorf A, Lehr C, Regenhardt J, Bokemeyer C, Ruf W, Rolling C, Langer F. Inhibition of protein disulfide isomerase with PACMA-31 regulates monocyte tissue factor through transcriptional and posttranscriptional mechanisms. Thromb Res. 2022 Dec;220:48-59. doi: 10.1016/j.thromres.2022.09.024. Epub 2022 Sep 30. PMID: 36265413. 3: Xu Q, Zhang J, Zhao Z, Chu Y, Fang J. Revealing PACMA 31 as a new chemical type TrxR inhibitor to promote cancer cell apoptosis. Biochim Biophys Acta Mol Cell Res. 2022 Oct;1869(10):119323. doi: 10.1016/j.bbamcr.2022.119323. Epub 2022 Jul 4. PMID: 35793738. 4: Powell LE, Foster PA. Protein disulphide isomerase inhibition as a potential cancer therapeutic strategy. Cancer Med. 2021 Apr;10(8):2812-2825. doi: 10.1002/cam4.3836. Epub 2021 Mar 20. PMID: 33742523; PMCID: PMC8026947. 5: Krajewski D, Polukort SH, Gelzinis J, Rovatti J, Kaczenski E, Galinski C, Pantos M, Shah NN, Schneider SS, Kennedy DR, Mathias CB. Protein Disulfide Isomerases Regulate IgE-Mediated Mast Cell Responses and Their Inhibition Confers Protective Effects During Food Allergy. Front Immunol. 2020 Dec 22;11:606837. doi: 10.3389/fimmu.2020.606837. PMID: 33414789; PMCID: PMC7783394. 6: Young HS, McGowan LM, Jepson KA, Adams JC. Impairment of cell adhesion and migration by inhibition of protein disulphide isomerases in three breast cancer cell lines. Biosci Rep. 2020 Oct 30;40(10):BSR20193271. doi: 10.1042/BSR20193271. PMID: 33095243; PMCID: PMC7584814. 7: Popielarski M, Ponamarczuk H, Stasiak M, Watała C, Świątkowska M. Modifications of disulfide bonds in breast cancer cell migration and invasiveness. Am J Cancer Res. 2019 Aug 1;9(8):1554-1582. PMID: 31497343; PMCID: PMC6727000. 8: Won JK, Yu SJ, Hwang CY, Cho SH, Park SM, Kim K, Choi WM, Cho H, Cho EJ, Lee JH, Lee KB, Kim YJ, Suh KS, Jang JJ, Kim CY, Yoon JH, Cho KH. Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma. Hepatology. 2017 Sep;66(3):855-868. doi: 10.1002/hep.29237. Epub 2017 Jul 20. PMID: 28439950. 9: Vatolin S, Phillips JG, Jha BK, Govindgari S, Hu J, Grabowski D, Parker Y, Lindner DJ, Zhong F, Distelhorst CW, Smith MR, Cotta C, Xu Y, Chilakala S, Kuang RR, Tall S, Reu FJ. Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma. Cancer Res. 2016 Jun 1;76(11):3340-50. doi: 10.1158/0008-5472.CAN-15-3099. Epub 2016 Apr 6. PMID: 27197150. 10: Xu S, Butkevich AN, Yamada R, Zhou Y, Debnath B, Duncan R, Zandi E, Petasis NA, Neamati N. Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16348-53. doi: 10.1073/pnas.1205226109. Epub 2012 Sep 17. PMID: 22988091; PMCID: PMC3479552.