Actr-28. Phase 1 Dose Escalation Trial of the Safety of BMX-001 Concurrent With Radiation Therapy and Temozolomide in Newly Diagnosed Patients With High-Grade Gliomas

Peters, Katherine B.; Kirkpatrick, John P.; Batinić‐Haberle, Ines; Affronti, Mary Lou; Woodring, Sarah; Iden, Deborah; Panta, Sujata; Lipp, Eric; Healy, Patrick; Herndon, James E.; Spasojević, Ivan; Penchev, Sara; Gad, Shayne C.; Siberstein, David; Johnson, Margaret; Randazzo, Dina; Desjardins, Annick; Friedman, Henry S.; Ashley, David M.; Crapo, James D.

doi:10.1093/neuonc/noy148.061

Cited by 2 publications

(6 citation statements)

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“…Anticancer effects were demonstrated, while normal tissue was protected by MnPs, see also under "Molecular Pathways Affected by Mn Porphyrins in Cancer and Normal Cell" [3,68,112,113]. MnTnBuOE-2-PyP 5+ was found safe and well-tolerated in Phase I clinical trial on glioma [13] and is now in four Phase II clinical trials with the primary goal of demonstrating the radioprotection of normal tissues with cancer patients (Figure 4). Its efficacy is being tested in Phase II trials on the radioprotection of normal tissue with glioma patients (in combination with radiation and temozolomide, NCT02655601), head and neck cancer patients (in combination with radiation and cisplatin, NCT02990468), and anal squamous cell carcinoma patients (in combination with 5fluorouracil/mitomycin, NCT03386500), as well as on the radioprotection of normal brain in cancer patients who suffer…”

Section: Mntnbu-2-pyp 5+ a Clinical Candidate As A Cancer Radio-anmentioning

confidence: 99%

“…For the large part of this review, we have focused on MnTnBuOE-2-PyP 5+ due to its clinical relevance in cancer therapy. It was shown safe and well tolerated in Phase I clinical trial, where initial data suggest its efficacy [13][14][15]; it is now in several Phase II clinical trials.…”

Section: Design Of Mn Porphyrins As Sod Mimicsmentioning

confidence: 99%

“…Out of the 3 MnPs, MnTE-2-PyP 5+ has the safest toxicity profile, but the data demonstrate that MnTnBuOE-2-PyP 5+ poses no genotoxic risk to humans [55,56]. Both compounds proved to be safe and well tolerated in Phase I, and both progressed to the Phase II clinical trials [13][14][15].…”

Section: Bioavailability Of Mn Porphyrinsmentioning

confidence: 99%

“…Figure 4: MnTnBuOE-2-PyP 5+ (BMX-001) in four Phase II clinical trials. MnTnBuOE-2-PyP 5+ was shown safe and well tolerated in a Phase I trial on glioma patients [13] and was then forwarded into Phase II trials. Initial data from the Phase I trial suggest the therapeutic potential of MnTnBuOE-2-PyP 5+ with glioma patients [14,15].…”

Section: Ascorbate Enhances the Anticancer Radioand Chemosensitizing mentioning

confidence: 99%

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H₂O₂‐Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways

Batinić‐Haberle

Tovmasyan

Huang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Mn(III) ortho-N-alkyl- and N-alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO-, H2O2, H2S, CO3•-, ascorbate, and GSH). Moreover, the ability of MnPs to oxidatively modify activities of numerous proteins has emerged as their major mechanism of action both in normal and in cancer cells. Among those proteins are transcription factors (NF-κB and Nrf2), mitogen-activated protein kinases, MAPKs, antiapoptotic bcl-2, and endogenous antioxidative defenses. The lead Mn porphyrins, namely, MnTE-2-PyP5+ (BMX-010, AEOL10113), MnTnBuOE-2-PyP5+ (BMX-001), and MnTnHex-2-PyP5+, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE-2-PyP5+ into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP5+ is in Phase II clinical trial on atopic dermatitis and itch.

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Section: Mntnbu-2-pyp 5+ a Clinical Candidate As A Cancer Radio-anmentioning

confidence: 99%

Section: Design Of Mn Porphyrins As Sod Mimicsmentioning

confidence: 99%

Section: Bioavailability Of Mn Porphyrinsmentioning

confidence: 99%

Section: Ascorbate Enhances the Anticancer Radioand Chemosensitizing mentioning

confidence: 99%

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H₂O₂‐Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways

Batinić‐Haberle

Tovmasyan

Huang

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…A potential advantage of metalloporphyrin-based antibacterials is their low toxicity to eukaryotic cells [ 7 , 14 ]. Various porphyrin-based therapeutics, including manganese porphyrin-based SOD mimics, have shown minimal toxicity to laboratory animals and are now in five phase II human clinical trials [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. In our preliminary studies, we found that cationic Mn porphyrins (MnPs) did not show measurable toxicity to human cell cultures and to mice at concentrations tenfold higher than those killing E. coli (unpublished data).…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Activity of Synthetic Cationic Iron Porphyrins

2020

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Widespread antibiotic resistance demands new strategies for fighting infections. Porphyrin-based compounds were long ago introduced as photosensitizers for photodynamic therapy, but light-independent antimicrobial activity of such compounds has not been systematically explored. The results of this study demonstrate that synthetic cationic amphiphilic iron N-alkylpyridylporphyrins exert strong bactericidal action at concentrations as low as 5 μM. Iron porphyrin, FeTnHex-2-PyP, which is well tolerated by laboratory animals, efficiently killed Gram-negative and Gram-positive microorganisms. Its bactericidal activity was oxygen-independent and was controlled by the lipophilicity and accumulation of the compound in bacterial cells. Such behavior is in contrast with the anionic gallium protoporphyrin IX, whose efficacy depends on cellular heme uptake systems. Under aerobic conditions, however, the activity of FeTnHex-2-PyP was limited by its destruction due to redox-cycling. Neither iron released from the Fe-porphyrin nor other decomposition products were the cause of the bactericidal activity. FeTnHex-2-PyP was as efficient against antibiotic-sensitive E. coli and S. aureus as against their antibiotic-resistant counterparts. Our data demonstrate that development of amphiphilic, positively charged metalloporphyrins might be a promising approach in the introduction of new weapons against antibiotic-resistant strains.

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Actr-28. Phase 1 Dose Escalation Trial of the Safety of BMX-001 Concurrent With Radiation Therapy and Temozolomide in Newly Diagnosed Patients With High-Grade Gliomas

Cited by 2 publications

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H₂O₂‐Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways

H₂O₂‐Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways

Antibacterial Activity of Synthetic Cationic Iron Porphyrins

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Actr-28. Phase 1 Dose Escalation Trial of the Safety of BMX-001 Concurrent With Radiation Therapy and Temozolomide in Newly Diagnosed Patients With High-Grade Gliomas

Cited by 2 publications

References 0 publications

H2O2‐Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways

H2O2‐Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways

Antibacterial Activity of Synthetic Cationic Iron Porphyrins

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H₂O₂‐Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways

H₂O₂‐Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways