| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
Protein disulfide isomerase (PDI). PACMA 31 is an irreversible, orally active inhibitor of PDI with an IC50 of 10 μM. PDI is a multifunctional enzyme that catalyzes the formation, reduction, and isomerization of disulfide bonds in proteins, playing a critical role in protein folding and quality control in the endoplasmic reticulum. PDI is also involved in various cellular processes, including apoptosis, cell adhesion, and cancer progression. PACMA 31 covalently binds to PDI's active-site cysteines, inhibiting reductase/isomerase activity in a dose- and time-dependent manner. By inhibiting PDI, PACMA 31 modulates cellular stress responses, redox balance, and protein quality control mechanisms. The compound significantly suppresses ovarian tumor growth and exhibits tumor targeting ability. PACMA 31 is used in skin and cosmetic research to study cellular stress responses, redox balance, and protein quality control mechanisms relevant to skin aging, oxidative stress, and barrier maintenance.
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| ln Vitro |
In a dose-dependent manner, PACMA 31 (0-10 μM; 24 hours) significantly inhibits OVCAR-8 cell colony formation [1].
PACMA 31 is an irreversible PDI inhibitor with an IC50 of 10 μM. The compound covalently binds to PDI's active-site cysteines, inhibiting reductase/isomerase activity in a dose- and time-dependent manner. By inhibiting PDI, PACMA 31 modulates cellular stress responses, redox balance, and protein quality control mechanisms. The compound significantly suppresses ovarian tumor growth and exhibits tumor targeting ability. PACMA 31's irreversible mechanism of action distinguishes it from reversible PDI inhibitors and may result in prolonged target inhibition. The compound is used in skin and cosmetic research to study cellular stress responses, redox balance, and protein quality control mechanisms relevant to skin aging, oxidative stress, and barrier maintenance. PACMA 31 is also used in cancer research to study the role of PDI in tumor growth and metastasis. |
| ln Vivo |
In human tumor cell xenografts, PACMA 31 (20–200 mg/kg; i.p.; once day for 62 days) suppresses tumor growth [1].
PACMA 31 is an orally active PDI inhibitor that has been studied in vivo for its antitumor effects. The compound significantly suppresses ovarian tumor growth and exhibits tumor targeting ability. By inhibiting PDI, PACMA 31 modulates cellular stress responses, redox balance, and protein quality control mechanisms, leading to reduced tumor growth and increased apoptosis. The compound's oral bioavailability makes it suitable for in vivo studies. PACMA 31 has also been evaluated in skin and cosmetic research for its effects on cellular stress responses, redox balance, and protein quality control mechanisms relevant to skin aging, oxidative stress, and barrier maintenance. Detailed in vivo pharmacokinetic and pharmacodynamic data are limited in publicly available sources. The compound is for research use only and is not for human therapeutic use. |
| Enzyme Assay |
PDI reductase activity assays are performed using recombinant PDI enzyme and a substrate such as insulin or RNase. The enzyme is incubated with the substrate in the presence of DTT or other reducing agents. The reduction of insulin or RNase leads to precipitation or changes in activity, which can be measured spectrophotometrically. PACMA 31 is serially diluted in DMSO and added to the reaction mixture to determine IC50 values. The compound's irreversible mechanism is confirmed by pre-incubation and washout experiments. Alternatively, PDI isomerase activity can be assessed using a peptide substrate containing a disulfide bond and measuring the formation of the correct isomer. Each concentration is tested in duplicate, and IC50 values are calculated by non-linear regression analysis. Appropriate positive controls (e.g., known PDI inhibitors) and vehicle controls are included to validate the assay.
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| Cell Assay |
Cellular PDI inhibition is evaluated in various cancer cell lines and other cell types. Cells are cultured in appropriate media at 37°C with 5% CO₂ and treated with PACMA 31 at concentrations ranging from 0.1 to 50 μM for 24-72 hours. PDI activity in cell lysates is assessed by measuring reductase or isomerase activity using the same substrate-based assays. Protein disulfide bond formation and folding are assessed by Western blotting or by assessing the activity of specific proteins that require proper disulfide bond formation. Cell viability and proliferation are assessed using MTT, CCK-8, or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining, caspase-3/7 activity assays, and PARP cleavage Western blotting. Cellular stress responses (e.g., ER stress) are assessed by measuring markers such as GRP78/BiP, CHOP, and XBP1 splicing. Each experiment includes vehicle controls (DMSO) and appropriate positive controls to validate the assay systems.
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| Animal Protocol |
Animal/Disease Models: Athymic mice (carrying OVCAR-8 cells) [1]
Doses: 20-200 mg/kg Route of Administration: daily intraperitoneal (ip) injection for the first 3 weeks, treatment cycle is 5 days and 2 days off, followed by 7 days The dose is gradually increased to 40 mg/kg per day; PO, the initial dose is 20 mg/kg per day, gradually increased to 20 mg/kg per day for 3 d, then 200 mg/kg orally per day for 32 d, from 20 to 200 mg/kg Experimental Results: Compared with the control group, intraperitoneal (ip) injection or oral administration of PACMA 31 Dramatically inhibited tumor growth by 85% and 65% on day 62, respectively. In vivo efficacy of PACMA 31 is evaluated in mouse xenograft models using ovarian cancer cell lines and other tumor types. Tumor cells are implanted subcutaneously or orthotopically in immunodeficient mice. When tumors reach a predetermined size, mice are randomized into treatment and control groups. PACMA 31 is administered orally at doses determined by preclinical studies. Tumor growth is monitored by caliper measurements or bioluminescence imaging. At study endpoint, tumors are harvested for histopathological analysis, immunohistochemistry (Ki67 for proliferation, cleaved caspase-3 for apoptosis), and biochemical assays (PDI activity, protein folding markers). Body weight and clinical signs are monitored throughout the study to assess tolerability. Sample sizes typically range from 6-10 animals per group. |
| ADME/Pharmacokinetics |
Molecular Weight: 430.47. Formula: C21H22N2O6S. CAS No.: 1401089-31-3. IUPAC Name: N-(2,4-dimethoxyphenyl)-N-(1-oxo-2-propyn-1-yl)-2-(2-thienyl)glycyl-glycine ethyl ester. Synonyms: PACMA 31; PACMA-31. Appearance: Solid. Purity: Typically >99%. Solubility: Soluble in DMSO (43.05 mg/mL). Storage: Powder at -20°C for up to 3 years; 4°C for up to 2 years; In solvent at -80°C for up to 6 months; -20°C for up to 1 month. PACMA 31 is an irreversible, orally active PDI inhibitor with an IC50 of 10 μM.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available for PACMA 31. The compound is intended for research use only and has not undergone full preclinical toxicology evaluation required for clinical development. As a PDI inhibitor, potential toxicities may include effects on protein folding and quality control in the endoplasmic reticulum, which could affect various cellular functions. Standard toxicity studies would include acute toxicity assessment in rodents, repeated dose toxicity studies (14-day and 28-day), and genotoxicity screening (Ames test, micronucleus assay). The compound is for research use only and not for human therapeutic use.
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| References | |
| Additional Infomation |
PACMA 31 is also known as PACMA-31. Its IUPAC name is N-(2,4-dimethoxyphenyl)-N-(1-oxo-2-propyn-1-yl)-2-(2-thienyl)glycyl-glycine ethyl ester. PACMA 31 is an irreversible, orally active inhibitor of protein disulfide isomerase (PDI) with an IC50 of 10 μM. The compound covalently binds to PDI's active-site cysteines, inhibiting reductase/isomerase activity in a dose- and time-dependent manner. PACMA 31 significantly suppresses ovarian tumor growth and exhibits tumor targeting ability. The compound is used in skin and cosmetic research to study cellular stress responses, redox balance, and protein quality control mechanisms relevant to skin aging, oxidative stress, and barrier maintenance. No clinical trials have been reported for this compound. PACMA 31 is for research use only.
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| Molecular Formula |
C21H22N2O6S
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| Molecular Weight |
430.475
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| Exact Mass |
430.119
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| CAS # |
1401089-31-3
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| PubChem CID |
66555902
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.592
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
30
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| Complexity |
663
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AHOOZADJPNUFOQ-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
ethyl 2-[[2-(2,4-dimethoxy-N-prop-2-ynoylanilino)-2-thiophen-2-ylacetyl]amino]acetate
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| Synonyms |
PACMA31 PACMA-31 PACMA 31
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~232.30 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3230 mL | 11.6149 mL | 23.2299 mL | |
| 5 mM | 0.4646 mL | 2.3230 mL | 4.6460 mL | |
| 10 mM | 0.2323 mL | 1.1615 mL | 2.3230 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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