PNC-27 Research

PNC-27 research is entirely preclinical, and every efficacy finding described below comes from cell culture or from animal models ^[18]. PNC-27 is a research chemical only, not an approved medicine in the United States and not for human consumption ^[16][22]. No registered clinical trial of this peptide has ever existed, in any registry checked ^[18].

What PNC-27 is

PNC-27 is a 32-residue synthetic chimeric peptide, joining residues 12 to 26 of human p53, the HDM-2 binding domain, to a 17-residue membrane-residency leader ^[1][2]. That leader is KKWKMRRNQFWVKVQRG, derived from the Drosophila Antennapedia homeodomain, and the primary literature calls it the penetratin or Antp sequence ^[1][11]. It is a modified variant rather than penetratin as usually written, RQIKIWFQNRRMKWKK. PubChem records CAS 1159861-00-3 as CID 16201774, with a formula and molecular weight matching the published 32-residue sequence ^[2][20].

Names that are easy to confuse

• PNC-28 is a shorter analog built from p53 residues 17 to 26, and it is not PNC-27 ^[14][15].
• PNC-26 is the p53 12-26 fragment with no leader attached, used as an inactive control ^[15].
• PNC-29 is a scrambled control peptide carrying the same leader ^[12].
• OM-301 is the sponsor Oncolyze's development name for this peptide ^[19].

The human record

Searches of ClinicalTrials.gov, the EU Clinical Trials Register, CTIS and ISRCTN return zero registered trials for PNC-27, OM-301 or Oncolyze ^[18].

One ex vivo study used human tumor tissue without dosing a patient ^[6]. PNC-27 was cytotoxic to primary epithelial ovarian cancer cells isolated from two patients ^[6]. The control peptide PNC-29 was not cytotoxic to those cells ^[6]. Those cells were treated in a dish, and no patient received the peptide ^[6].

There is also no safety database, and openFDA queries return no adverse event and no enforcement records for PNC-27 ^[22]. That absence reflects a lack of surveillance rather than tolerability ^[18][22].

FDA findings on PNC-27 sold to patients

In January 2017 the FDA warned consumers not to buy or use PNC-27, then sold through a website as a cancer treatment ^[17]. An FDA laboratory had found the bacterium Variovorax paradoxus in a PNC-27 solution sample for inhalation ^[17]. The agency repeats that finding on its live health fraud page ^[16].

In a 27 March 2017 page update, the FDA reported Ralstonia insidiosa in another PNC-27 inhalation sample ^[17].

That same page records PNC-27 being sold in several dosage forms, including nebulized and intravenous solutions and suppositories ^[17]. As of 27 March 2017 the agency had received no illness reports related to PNC-27 ^[17].

Proposed mechanism of action

The originating laboratory argues that PNC-27 binds HDM-2 displayed on the outer plasma membrane of cancer cells and forms pores ^[3][11]. Solution NMR showed amphipathic helix-coil-helix structures in membrane-mimetic solvent, the property proposed to explain membrane disruption ^[2]. In vitro, HDM-2 was detected in the membranes of several cancer cell lines but not in several untransformed lines ^[3]. Transfecting membrane-targeted HDM-2 into a resistant untransformed line made it susceptible in vitro ^[3]. Immuno-scanning electron microscopy found labeled PNC-27 and HDM-2 in ring-shaped structures at pores on cancer cells in vitro ^[11]. No pores formed in the untransformed fibroblasts treated in that same work ^[11]. In vitro work also indicates that the intact chimera does the killing, and that the naked p53 fragment without the leader is inactive ^[4][15].

The founding paper reported no effect on normal cells in culture, including human cord blood derived stem cells ^[1]. It also reported killing in p53 null cancer cells in culture, so the proposed mechanism is p53 independent ^[1].

PNC-27 research in cells and animals

The strongest independent result is in acute myeloid leukemia ^[9]. An independent group reported membrane HDM-2 on human and mouse AML blasts in vitro, but not on normal hematopoietic stem cells ^[9]. In mouse transplant experiments, PNC-27 killed both bulk blasts and leukemia stem cells ^[9]. That animal work supports the selectivity phenotype, while proposing a different mechanism involving E-cadherin ubiquitination and degradation rather than pore formation ^[9].

A second independent group contradicts the strong version of that selectivity ^[5]. Yang and colleagues measured PNC-27 IC50 values of 15 to 20 micromolar in tumor cell lines, against above 50 micromolar in normal cell lines, in vitro ^[5]. That is a window of roughly two to three fold ^[5]. PNC-27 was not without effect on normal cells in that study ^[5]. Swapping the Antennapedia leader for other carriers abolished selectivity in vitro, and pairing that same leader with unrelated cargoes recreated it ^[5]. They concluded that the p53-derived domain does not determine selectivity ^[5]. They proposed instead that the leader binds chondroitin sulfate on tumor cell surfaces, with death by mitochondrial disruption ^[5]. Removing endogenous chondroitin sulfate reduced killing in tumor cells in vitro ^[5]. They also frame that death as apoptosis, against the originating group's necrosis and pore model ^[5][12].

No published rebuttal has been found sixteen years on, and the originating group's 2024 mechanism review neither cites Yang and colleagues nor discusses chondroitin sulfate ^[12]. That group's own wording is also softer than the popular framing, since its 2024 review describes untransformed cell lines as expressing low or no observable membrane HDM-2 ^[12]. Low is not zero, so selectivity on their own account is a concentration-dependent window ^[12]. Their most recent in vitro study reports an IC50 of 12.4 micromolar against a cervical carcinoma line, with an untransformed cervical line reported unaffected ^[13].

A third independent group used PNC-27 as a targeting ligand rather than testing its selectivity claim ^[8]. A PNC-27 liposome conjugate improved doxorubicin efficacy in an HDM2-positive mouse colon tumor model, but not in an HDM2-negative mouse melanoma model ^[8]. That animal result is consistent with HDM2 dependence ^[8]. That study tested a conjugate rather than the free peptide ^[8]. A fourth independent group used these peptides as delivery ligands, not as a test of selectivity ^[23].

The remaining evidence cited here is one author network repeating one assay design across ovarian, colon, cervical and leukemia cell lines ^[7][10][13]. A mouse ovarian model from that network reported that cells surviving paclitaxel raised surface MDM-2 and became more susceptible to PNC-27 ^[7]. Apart from the conjugate study, no independent replication for any solid tumor indication in a live animal was found ^[8][9]. The pancreatic in vivo work most often quoted in this space used PNC-28, a different peptide ^[14].

Regulatory status

PNC-27 is not an approved medicine in the United States ^[16][22]. Two FDA orphan drug designations are reported on OM-301, announced for acute myeloid leukemia in January 2022 and for multiple myeloma in April 2023 ^[19]. They are corroborated by the sponsor and by trade press, not by a retrieved FDA orphan register record ^[19]. Orphan designation is a development incentive, and it is not approval, not evidence of efficacy, and not evidence of safety ^[19].

The sponsor stated an intention to open a first-in-human phase 1/2 trial of OM-301 in 2023 ^[19]. As of August 2026 no such trial appears in any registry checked ^[18]. European agency status could not be verified here, and no European application of any kind was found ^[18].

Conflicts of interest in the literature

One author network, spanning SUNY Downstate, Drexel and Thomas Jefferson, produced most of this evidence base ^[12]. Several of its papers sit in a single low-impact quarterly ^[6][7][13]. US patent 8,822,419, filed on 2 October 2009, names three of the PNAS 2010 authors as inventors and claims PNC-27 ^[21]. That PNAS paper, published online in January 2010, declares no conflict of interest ^[3]. The same group's 2022 paper does disclose the patents properly ^[11]. Its 2024 review discloses one author's company employment, then states that the remaining authors had no commercial relationship ^[12]. One of those remaining authors is a named inventor on that patent ^[21].

The strongest independent study is independent in authorship but not in materials, because Wang and colleagues declare that Oncolyze supplied PNC-27 and its controls ^[9].

Conclusion

PNC-27 is an early-stage research peptide, and no human has ever received it in a registered trial ^[18]. Its selectivity phenotype has partial independent support in an animal leukemia model ^[9]. Both the size of that selectivity and its mechanism are disputed by an in vitro study, and no published reply from the originating group has been found ^[5][12]. FDA laboratories also found bacterial contamination in consumer-channel PNC-27 twice in 2017 ^[17].

Evidence and identity FAQ

Has PNC-27 been tested in humans? No registered human trial of PNC-27 has ever existed, in any of the registries checked ^[18]. One ex vivo study treated primary ovarian cancer cells from two patients in a dish, and no patient received the peptide ^[6].

Is PNC-27 the same as PNC-28? They are different peptides, and PNC-28 is a shorter analog built from p53 residues 17 to 26 ^[14][15]. PNC-26 and PNC-29 are control peptides rather than active compounds ^[12][15].

Has the selectivity claim been independently replicated? The picture is split rather than settled ^[5][9]. One independent group supported the selectivity phenotype in mouse AML models, while proposing a different mechanism of killing ^[9]. A second independent group measured a window of roughly two to three fold in vitro, and attributed it to the leader sequence ^[5].

Do the FDA orphan drug designations mean PNC-27 is approved? Orphan designation is a development incentive, not approval, and not evidence of efficacy or safety ^[19]. The two designations are reported on the development name OM-301 ^[19]. They are corroborated by the sponsor and by trade press, not by a retrieved FDA orphan register record ^[19].

References

1. 1

   Kanovsky M, Raffo A, Drew L, et al. Peptides from the amino terminal mdm-2-binding domain of p53, designed from conformational analysis, are selectively cytotoxic to transformed cells. Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12438-43. PMID 11606716. DOI: 10.1073/pnas.211280698 (founding paper; the peptide was not yet named PNC-27, so a "PNC-27" PubMed query does not return it)
2. 2

   Rosal R, Pincus MR, Brandt-Rauf PW, et al. NMR solution structure of a peptide from the mdm-2 binding domain of the p53 protein that is selectively cytotoxic to cancer cells. Biochemistry. 2004 Feb 24;43(7):1854-61. PMID 14967026. DOI: 10.1021/bi035718g
3. 3

   Sarafraz-Yazdi E, Bowne WB, Adler V, et al. Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes. Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1918-23. PMID 20080680. DOI: 10.1073/pnas.0909364107
4. 4

   Sookraj KA, Bowne WB, Adler V, et al. The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide. Cancer Chemother Pharmacol. 2010 Jul;66(2):325-31. PMID 20182728. DOI: 10.1007/s00280-009-1166-7
5. 5

   Yang H, Liu S, Cai H, et al. Chondroitin sulfate as a molecular portal that preferentially mediates the apoptotic killing of tumor cells by penetratin-directed mitochondria-disrupting peptides. J Biol Chem. 2010 Aug 13;285(33):25666-76. PMID 20484051. DOI: 10.1074/jbc.M109.089417 (independent group, West China Hospital, Sichuan University; full text at PMC2919130)
6. 6

   Sarafraz-Yazdi E, Gorelick C, Wagreich AR, et al. Ex vivo efficacy of anti-cancer drug PNC-27 in the treatment of patient-derived epithelial ovarian cancer. Ann Clin Lab Sci. 2015 Fall;45(6):650-8. PMID 26663795.
7. 7

   Alagkiozidis I, Gorelick C, Shah T, et al. Synergy between paclitaxel and anti-cancer peptide PNC-27 in the treatment of ovarian cancer. Ann Clin Lab Sci. 2017 May;47(3):271-81. PMID 28667027.
8. 8

   Darban SA, Badiee A, Jaafari MR. PNC27 anticancer peptide as targeting ligand significantly improved antitumor efficacy of Doxil in HDM2-expressing cells. Nanomedicine (Lond). 2017 Jun;12(12):1475-90. PMID 28565974. DOI: 10.2217/nnm-2017-0069 (independent group; includes BALB/c C26 and C57BL/6 B16F0 mouse tumor models)
9. 9

   Wang H, Zhao D, Nguyen LX, et al. Targeting cell membrane HDM2: a novel therapeutic approach for acute myeloid leukemia. Leukemia. 2020 Jan;34(1):75-86. PMID 31337857. DOI: 10.1038/s41375-019-0522-9 (independent authorship, City of Hope and collaborators; declared conflict states that Oncolyze, Inc. provided PNC-27, PNC-26 and PNC-29 for the study)
10. 10

    Thadi A, Lewis L, Goldstein E, et al. Targeting membrane HDM-2 by PNC-27 induces necrosis in leukemia cells but not in normal hematopoietic cells. Anticancer Res. 2020 Sep;40(9):4857-67. PMID 32878773. DOI: 10.21873/anticanres.14488
11. 11

    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. Biomedicines. 2022 Apr 20;10(5):945. PMID 35625682. DOI: 10.3390/biomedicines10050945 (this paper discloses the PNC-27 and PNC-28 patents)
12. 12

    Pincus MR, Silberstein M, Zohar N, et al. Poptosis or peptide-induced transmembrane pore formation: a novel way to kill cancer cells without affecting normal cells. Biomedicines. 2024 May 22;12(6):1144. PMID 38927351. DOI: 10.3390/biomedicines12061144 (full text at PMC11201261 checked for any citation of reference 5; there is none)
13. 13

    Krzesaj PK, Seydafkan S, Miller AI, et al. HDM-2-targeting peptide PNC-27 kills cervical cancer cells but not normal cervical cells. Ann Clin Lab Sci. 2025 May;55(3):347-53. PMID 40750238.
14. 14

    Michl J, Scharf B, Schmidt A, et al. PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo. Int J Cancer. 2006 Oct 1;119(7):1577-85. PMID 16688716. DOI: 10.1002/ijc.22029 (PNC-28, not PNC-27)
15. 15

    Bowne WB, Sookraj KA, Vishnevetsky M, et al. The penetratin sequence in the anticancer PNC-28 peptide causes tumor cell necrosis rather than apoptosis of human pancreatic cancer cells. Ann Surg Oncol. 2008 Dec;15(12):3588-600. PMID 18931881. DOI: 10.1245/s10434-008-0147-0 (defines PNC-26 as p53 aa12-26 without penetratin, used as a control; the active peptide in this paper is PNC-28)
16. 16

    US Food and Drug Administration. Questions and answers: FDA alerts companies to stop illegal sale of products claiming to treat cancer. fda.gov/consumers/health-fraud-scams. Live page, retrieved 2026-08-28: "in January 2017, an FDA laboratory discovered the bacteria Variovorax paradoxus in a sample of PNC-27, an unapproved drug product promoted as a treatment or cure for cancer."
17. 17

    US Food and Drug Administration. FDA warns cancer patients not to use PNC-27 products for treatment. Original URL fda.gov/drugs/drug-safety-and-availability/fda-warns-cancer-patients-not-use-pnc-27-products-treatment now returns HTTP 404, confirmed 2026-08-28. Full text retrieved from the Internet Archive snapshot of 2026-03-07; page content current as of 27 March 2017. Carries the 1/10/2017 warning, the Variovorax paradoxus finding in "a PNC-27 solution sample for inhalation", the 3/27/2017 update reporting Ralstonia insidiosa in another inhalation sample, the dosage forms, and the statement that no illness reports had been received.
18. 18

    Trial registry and regulatory sweep, re-run 2026-08-28. ClinicalTrials.gov API v2 with countTotal=true returns 0 for PNC-27, PNC27, OM-301, OM301 and Oncolyze. EU Clinical Trials Register returns no matching trials, CTIS returns totalRecords 0, and ISRCTN returns an empty set. No European application of any kind was found. EMA status is unverified at agency level, because ema.europa.eu is access-gated.
19. 19

    Oncolyze, Inc. Science page, oncolyze.com/science, retrieved 2026-08-28: "in vivo preclinical data using OM-301 (previously, PNC-27)". Orphan drug designations for AML (announced January 2022) and multiple myeloma (announced April 2023), and the stated 2023 phase 1/2 intention, are sourced from the sponsor and from trade coverage. FDA's Orphan Drug Designations and Approvals database was bot-challenged and returned no primary record.
20. 20

    NCBI PubChem. CAS 1159861-00-3 round-tripped to CID 16201774, re-verified 2026-08-28: C188H293N53O44S, molecular weight 4032.
21. 21

    US Patent 8,822,419 B2. "Membrane resident peptide in anti-cancer peptides causes tumor cell necrosis rather than apoptosis of cancer cells." Filed 2 October 2009, granted 2 September 2014, assigned to the Research Foundation of the State University of New York. Inventors include Matthew R. Pincus, Josef Michl and Ehsan Sarafraz-Yazdi. Claims PNC-27 and PNC-28.
22. 22

    US Food and Drug Administration. openFDA drug/label, drug/ndc, drug/drugsfda, drug/event (FAERS) and drug/enforcement APIs, field-qualified substance-name and generic-name queries. All returned NOT_FOUND for PNC-27; sweep dated 2026-08-28.
23. 23

    Mokhtarzadeh A, Parhiz H, Hashemi M, et al. P53-Derived peptides conjugation to PEI: an approach to producing versatile and highly efficient targeted gene delivery carriers into cancer cells. Expert Opin Drug Deliv. 2016;13(4):477-91. PMID 26654047. DOI: 10.1517/17425247.2016.1126245 (independent delivery group; cited for census completeness, not as a replication)