PNC-27
PNC-27

PNC-27

$120
PNC-27: 10MG

PNC-27 Overview

PNC-27 is a chimeric p53 penetrating peptide consisting of a structural domain (residues 12-26) in the p53 protein that binds to HDM-2 and a transmembrane penetrating peptide sequence. It forms a transmembrane pore by binding to HDM-2 protein in cancer cell membranes, leading to membrane lysis and necrosis of cancer cells, while being non-toxic to normal cells. This selective mechanism has led to significant anticancer activity in a variety of cancer cells (e.g., breast cancer, pancreatic cancer, acute myeloid leukemia, etc.). PNC-27 is unique in that its mechanism of action does not depend on the functional state of p53, which makes it potentially advantageous for the treatment of tumors that are refractory to conventional p53-dependent therapies. In addition, PNC-27 has shown synergistic effects with chemotherapeutic agents such as paclitaxel, further enhancing its therapeutic potential.

Peptide Information

Property Value
Peptide Sequence H-D-Leu-D-Thr-D-Leu-D-Arg-D-Lys-D-Glu-D-Pro-D-Ala-D-Ser-D-Glu-D-Ile-D-Ala-D-Gln-D-Ser-D-Ile-D-Leu-D-Glu-D-Ala-D-Tyr-D-Ser-D-Gln-D-Asn-Gly-D-Trp-D-Ala-D-Asn-D-Arg-D-Arg-D-Ser-Gly-Gly-Lys-Arg-Pro-DL-Pro-DL-Pro-Arg-Arg-Arg-Gln-Arg-Arg-Lys-Lys-Arg-Gly-OH
Molecular Formula C188H293N53O44S
Molecular Weight 4031.73 g/mol
CAS Number 1159861-00-3
PubChem CID
Synonyms

 

PNC-27 Research


What are the applications of PNC-27?

1, Treatment of leukemia: 

PNC-27 is able to bind HDM-2 protein on the membrane of cancer cells and induce the formation of cytotoxic transmembrane pores. In a study of human non-stem cell acute myeloid leukemia cell lines, HDM-2 was found to be highly expressed in the membranes of U937 (acute monocytic leukemia), OCI-AML3 (acute granulomonocytic leukemia), and HL60 (acute promyelocytic leukemia) cells.PNC-27 binds to HDM-2 on membranes, and induces necroptosis and LDH (lactate dehydrogenase) release within 4 hours. (LDH) release within 4 hours. Targeting HDM-2 on the cell membrane may be a potential strategy for the treatment of leukemia.PNC-27 exhibited significant anti-leukemic activity in several leukemia cell lines by targeting Membrane HDM-2 [1].

2. Induces tumor cell lysis

Acts as an intact peptide: 

Several studies have shown that PNC-27 induces tumor cell lysis as an intact peptide rather than as a fragment. For example, in a study of MCF-7 breast cancer cells and untransformed MCF-10-2A mammary epithelial cells, cells were treated with PNC-27 with green fluorescently labeled amino terminus and red fluorescently labeled carboxy terminus. The results showed a distinct punctate yellow fluorescence on the cancer cell membrane at 30 min, indicating that the intact peptide was present on the cancer cell membrane and increased with cancer cell lysis. In contrast, untransformed MCF-10-2A cells initially showed uniform yellow membrane fluorescence, but then disappeared. Unlike cancer cells, these untransformed cells remained viable. This suggests that PNC-27 induces membrane cleavage in cancer cells by acting as an entire peptide, rather than a fragment[2].

Binding to HDM-2 to form pore structures: 

PNC-27 contains an HDM-2-binding structural domain and a cell-penetrating peptide (CPP) presequence, which induces the formation of pore structures by binding to HDM-2 on the cell membrane, leading to tumor cell lysis and necrosis. Conformational energy calculations showed that PNC-27 forms a complex with HDM-2 in a 1:1 ratio, with the leading sequence pointing away from the complex. Immunoscanning electron microscopy studies revealed the presence of multiple 6 nm and 15 nm labeled gold particles at a ratio of approximately 1:1 in the pores on the surface of cancer cells treated with PNC-27, suggesting that these complexes are important for pore structure. In contrast, no pores were formed in control, untransformed fibroblasts treated with PNC-27[3].

Pancreatic Cancer: 

The novel anticancer PNC-27 peptide induces necrosis of human pancreatic MiaPaCa-2 cancer cells in a dose-dependent manner, but is non-toxic to normal cells. Studies have shown that PNC-27, when combined with Gemzar, a chemotherapeutic agent used to treat pancreatic cancer, has a greater cytotoxic effect on MiaPaCa-2 cells than Gemzar or PNC-27 alone. This may be because the PNC-27-induced pores increase the permeability of cancer cells to Gemzar, allowing more Gemzar to target cancer cells [1].

Ovarian Cancer: 

In ovarian cancer cell lines SKOV-3 and OVCAR-3, HDM-2 protein is highly expressed at the cell membrane.PNC-27 co-localizes with HDM-2 at the cell membrane, leading to rapid cell necrosis. In contrast, in the non-transformed control cell line HUVEC, co-localization and cytotoxicity of PNC-27 was not observed due to minimal membrane HDM-2 expression[1].

Colon Cancer: 

PNC-27 selectively kills colon cancer stem cells. In six colon cancer cell lines, PNC-27 co-localized with membrane HDM-2 and caused cell death (tumor cell necrosis, high LDH release, membrane associated protein V and cysteine 3 negativity) only in cancer cells. In vivo, PNC-27 causes necrosis of tumor nodules but does not affect normal tissue [1].

3. Improved anti-tumor efficacy

Binding to Doxil: 

It has been found that PNC27 peptide, as a targeting ligand, can significantly enhance the anti-tumor efficacy of Doxil in HDM2-positive cancer cells. Different amounts of PNC27 peptide were inserted into Doxil, and flow cytometry and confocal analysis were performed on C26 colon cancer (HDM2-positive) and B16F0 melanoma (HDM2-negative) cells. The results showed that PNC27-Doxil exhibited significant cellular uptake and cytotoxicity in C26 cells, whereas these results were not observed in B16F0 cells. For example, PNC27-Doxil (100 PNC27 peptide) significantly increased the therapeutic efficacy of Doxil without affecting its biodistribution in C26 tumors [4].

4. Synergistic treatment of ovarian cancer with paclitaxel

Paclitaxel is widely used in the treatment of gynecological malignancies, but it targets tumor cells in the M phase of the cell cycle, with cells in other phases surviving and potentially leading to tumor recurrence.PNC-27 is a peptide synthesized from amino acids in the P53-MDM-2 binding domain that kills various cancer cell lines in a dose-dependent manner. Ovarian cancer ID8 cells exposed to paclitaxel were found to show increased expression of MDM-2 and increased sensitivity to PNC-27.The cytotoxic effect of PNC-27 is dependent on its binding to MDM-2, and blocking MDM-2 inhibits the killing effect of PNC-27. The heterodrug images of the dose combinations were synergistic, suggesting a synergistic effect between PNC-27 and paclitaxel [5]. In an intraperitoneal model of ovarian cancer (ID8), the addition of PNC-27 to weekly paclitaxel administration significantly reduced tumor growth. These data demonstrate a synergistic effect between PNC-27 and paclitaxel, with PNC-27 targeting cell-surviving paclitaxel and improving its antitumor effects.

5. Treatment of primary epithelial ovarian cancer

A study has established primary cultures of freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinoma. One of them was from mucinous cystadenocarcinoma and the other was from high-grade papillary plasmacytoid carcinoma. The therapeutic efficacy of PNC-27 was quantitatively assessed by qualitative light microscopic observation and MTT cell proliferation assay as well as measurement of lactate dehydrogenase (LDH). The results showed that PNC-27 inhibited the growth of human primary cancer cells freshly isolated from two ovarian epithelial carcinomas in a dose-dependent manner and was cytotoxic to them. The control peptide PNC-29 had no effect on primary cancer cells. In addition, PNC-27 is also cytotoxic to long-established and chemotherapy-resistant human ovarian cancer cell lines[6].

In summary, PNC-27, as a novel anticancer peptide, shows significant potential for application in a variety of cancer therapies. In the field of leukemia, PNC-27 exhibited selective killing effects on acute myeloid leukemia (e.g., U937, OCI-AML3, and HL60 cell lines) and p53-deficient K562 cells, and achieved highly efficient antitumor effects by inducing cell necrosis and lactate dehydrogenase release. In the treatment of ovarian cancer, the combination of PNC-27 and paclitaxel showed a synergistic effect, which could significantly inhibit tumor growth and still have killing activity against chemotherapy-resistant cells. In addition, the combination of PNC-27 with liposomal drugs (e.g. Doxil) as a targeting ligand can enhance the specific delivery and anti-tumor efficacy of the drug to HDM2-positive tumor cells. Its inhibitory effect on primary epithelial ovarian cancer progenitor cells further validates the clinical translational value. Currently, PNC-27 has entered phase I clinical trials, and more clinical studies are needed to validate its safety and long-term efficacy, so as to promote it as an innovative solution for cancer treatment.

Relevant Citations

[1] Thadi A, Gleeson E M, Khalili M, et al. Anti-Cancer Tumor Cell Necrosis of Epithelial Ovarian Cancer Cell Lines Depends on High Expression of HDM-2 Protein in Their Membranes[J]. Annals of Clinical and Laboratory Science, 2020,50(5):611-624. https://pubmed.ncbi.nlm.nih.gov/33067207/

[2] Sookraj K A, Bowne W B, Adler V, et al. The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide[J]. Cancer Chemotherapy and Pharmacology, 2010,66(2):325-331.DOI:10.1007/s00280-009-1166-7.

[3] Sarafraz-Yazdi E, Mumin S, Cheung D, et al. PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis[J]. Biomedicines, 2022,10(5).DOI:10.3390/biomedicines10050945.

[4] Darban S A, Badiee A, Jaafari M R. PNC27 anticancer peptide as targeting ligand significantly improved antitumor efficacy of Doxil in HDM2-expressing cells[J]. Nanomedicine, 2017,12(12):1475-1490.DOI:10.2217/nnm-2017-0069.

[5] Alagkiozidis I, Gorelick C, Shah T, et al. Synergy between Paclitaxel and Anti-Cancer Peptide PNC-27 in the Treatment of Ovarian Cancer (Retraction of Vol 47, Pg 271, 2017)[J]. Annals of Clinical and Laboratory Science, 2017,47(4). https://pubmed.ncbi.nlm.nih.gov/28667027/

[6] Sarafraz-Yazdi E, Gorelick C, Wagreich A R, et al. Ex vivo Efficacy of Anti-Cancer Drug PNC-27 in the Treatment of Patient-Derived Epithelial Ovarian Cancer[J]. Annals of Clinical and Laboratory Science, 2015,45(6):650-658. https://pubmed.ncbi.nlm.nih.gov/26663795/

For Research Use Only
This compound is provided exclusively for in vitro laboratory research. It is not intended for human or animal consumption, diagnosis, treatment, or medical use. Not for dietary, cosmetic, or veterinary purposes. This product has not been evaluated by the U.S. Food and Drug Administration or any other regulatory authority.

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By purchasing from Humatide, you confirm that you are a qualified researcher with the knowledge and facilities to safely handle and store research chemicals. All sales are final. Humatide assumes no liability for misuse, misrepresentation, or unintended consequences arising from the use of this product.

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The products provided on this website are intended exclusively for in vitro research. In vitro research (Latin: *in glass*, meaning in glassware) is conducted outside the human body. These products are not pharmaceuticals, have not been approved by the U.S. Food and Drug Administration (FDA), and must not be used to prevent, treat, or cure any medical condition, disease, or ailment. It is strictly prohibited by law to introduce these products into the human or animal body in any form.

Polypeptide Purity Control and Verification Technical System

Humatide.com provides peptides with purity exceeding 99%. Humatide achieves precise control and scientific verification of polypeptide purity by integrating advanced technologies and a full-process quality control system: In the synthesis stage, automated solid-phase peptide synthesis (SPPS) is employed to accurately assemble amino acid sequences. A gradient purification strategy ranging from medium-pressure liquid chromatography (MPLC) to preparative high-performance liquid chromatography (Prep-HPLC) is utilized, optimizing mobile phase composition and elution conditions based on the physicochemical properties of the target peptide (hydrophobicity, charge distribution, etc.) to efficiently remove impurities. For purity detection, reverse-phase high-performance liquid chromatography (RP-HPLC) serves as the core technique, separating components through the distribution difference of molecules between the stationary phase (hydrophobic packing) and the mobile phase (polar solvent). Purity is determined via retention time matching and peak area normalization. Meanwhile, electrospray ionization mass spectrometry (ESI-MS) is combined to precisely verify the molecular weight and composition through mass-to-charge ratio (m/z) analysis, eliminating structurally heterogeneous impurities. Quality management covers the entire chain from raw material acceptance, synthesis process monitoring to finished product release. A continuous quality fingerprint is constructed using multi-dimensional indicators (HPLC purity, MS molecular weight, solvent residue, etc.), and batch data traceability is achieved through a laboratory information management system (LIMS), ensuring each batch meets the prespecified purity standards. This system provides a reliable technical guarantee for preparing high-purity polypeptides through the organic integration of process optimization, multi-dimensional detection, and full-process quality control.

Concepts of High-Performance Liquid Chromatography (HPLC) and Mass Spectrometry (MS)

High-performance liquid chromatography (HPLC) is a separation technology widely used by Humatide for peptide purification. Driven by a high-pressure pump, the mobile phase carries samples through a chromatographic column packed with a specific stationary phase, achieving separation based on differences in the distribution coefficients of components between the two phases. It features high separation efficiency, fast analysis speed, and strong detection sensitivity, enabling precise capture of subtle differences between target peptides and impurities such as sequence analogs or deletion peptides.

Mass spectrometry (MS) is an analytical method that converts peptide molecules into gas-phase ions through ionization technology and separates/detects ions based on their mass-to-charge ratio (m/z). It can accurately determine the molecular weight of peptides and infer amino acid sequences through fragment ion information, serving as a key technology for verifying peptide structural correctness. The combination of these two techniques allows Humatide to establish a complete quality control system from both purity separation and structural confirmation perspectives. Both methods are high-precision peptide detection technologies that scientifically demonstrate the purity and composition of peptides ordered from Humatide.com.

Humatide is committed to translating cutting-edge analytical technologies into tangible quality assurance. Our peptide synthesis laboratories are equipped with high-resolution mass spectrometers and ultra-high-performance liquid chromatography systems. Through real-time detection and data comparison of samples at each production stage, we continuously optimize synthesis processes to ensure every peptide product is delivered to customers with exceptional purity.

Recommended Peptide Purity Levels

Humatide provides only the highest-purity peptides (purity ≥99%) for research and development. The minimum recommended peptide purity level for specific applications depends on the application:

• In biochemical research, peptides used for enzyme activity analysis typically require ≥85% purity.

• In drug development, peptides for preclinical trials must meet >98% high-purity standards to ensure biological activity and safety.

• For diagnostic applications (e.g., antigen peptides in immunoassays), recommended purity is 90%-95% to guarantee detection specificity and sensitivity.

Humatide is confident in the quality of all our products, implementing strict quality monitoring at every stage of peptide synthesis—from crude peptide purification to final product release. Through multi-step purification and verification processes, we ensure each batch meets or exceeds the purity requirements for specific applications. Examples of acceptable minimum purity levels are as follows:

High Purity (>95%)

• Polypeptide drug research and production

• Preparation of targeted therapeutic drugs

• Raw materials for biological diagnostic reagents (e.g., ELISA, immunoassay kits)

• Development of polypeptide vaccines (therapeutic/preventive)

• Preparation of targeting peptides for antibody-drug conjugates (ADCs)

• Polypeptide reagents for life science research (e.g., receptor agonists/antagonists)

• Research on targeting peptide modification for gene therapy vectors

• Development of polypeptide antibiotics/antimicrobial peptides

• Preparation of polypeptide hormone analogs (e.g., insulin analogs)

• Reference standards for biomarker detection

• Research on cell culture additives

• Synthetic peptides for protein structure analysis and functional studies

Moderate Purity (>85%)

• Early-stage activity screening in polypeptide drug research

• Peptide additives for industrial enzymes

• Signal peptide raw materials

• Surface modification of biomaterials (e.g., medical catheters, tissue engineering scaffolds)

• Preparation of agricultural antimicrobial peptides

• Cell adhesion research

• Raw materials for polypeptide surfactants/detergents

• Polypeptide reagents for preliminary mechanistic research in scientific studies

Lower Purity (>70%)

• Preliminary structure-activity relationship (SAR) studies

• Initial verification of protein binding

• Primary cytotoxicity screening

• High-throughput screening of polypeptide drug lead compounds


Please note

**We are not responsible for reconstitution or any issue that arise from it**


High-purity polypeptides are suitable for scenarios requiring strict purity. The ultra-high-purity peptides provided by Humatide can meet and exceed all prespecified purity standards.

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PNC-27
PNC-27
10MG
$120

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