WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H202242
CAS#: 149402-51-7
Description: Photochlor, also known as HTTP, is a lipophilic, second-generation, chlorin-based photosensitizer. Upon intravenous administration, HPPH selectively accumulates in the cytoplasm of cancer or pre-cancerous cells. When laser light is applied, a photodynamic reaction between HPPH and oxygen occurs, resulting in the production of cytotoxic free radicals and singlet oxygen and free radical-mediated cell death. Compared to the first-generation photosensitizer porfimer sodium, HPPH shows improved pharmacokinetic properties and causes only mild skin photosensitivity which declines rapidly within a few days after administration.
Hodoodo Cat#: H202242
Name: Photochlor
CAS#: 149402-51-7
Chemical Formula: C39H48N4O4
Exact Mass: 636.37
Molecular Weight: 636.820
Elemental Analysis: C, 73.56; H, 7.60; N, 8.80; O, 10.05
Synonym: HPPH; Photochlor; 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide-a; 2-(1'-hexyloxyethyl)-2-devinylpyropheophorbide-a.
IUPAC/Chemical Name: (3S,4S)-14-Ethyl-9-[1-(hexyloxy)ethyl]-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid
InChi Key: RBLODCJRUDEMCI-AMPGYZHFSA-N
InChi Code: InChI=1S/C39H50N4O4/c1-8-10-11-12-15-47-24(7)36-22(5)30-17-29-21(4)26(13-14-35(45)46)38(42-29)27-16-34(44)37-23(6)31(43-39(27)37)18-32-25(9-2)20(3)28(40-32)19-33(36)41-30/h17-19,21,24,26,31,40-41,43H,8-16H2,1-7H3,(H,45,46)/b28-19-,29-17-,32-18-/t21-,24?,26-,31?/m0/s1
SMILES Code: O=C(O)CC[C@@H]([C@@H]/1C)C2=NC1=C/C3=C(C)C(C(OCCCCCC)C)=C(N3)/C=C4C(C)=C(CC)/C(N/4)=C/C5C(C)=C6C(N5)=C2CC6=O
Appearance: Black solid powder
Purity: >95% (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, not in water
Shelf Life: >2 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: Clinical trial results: Photochlor is currently producing promising results in Phase II clinical trials. Forty-eight patients enrolled in Phases 1 and 2 clinical trials underwent two or more exposures to four graded doses (44.4, 66.6, 88.8 or 133.2 J/cm2) of artificial solar-spectrum light (SSL) before and after administration of Photochlor at a dose of 2.5, 3, 4, 5 or 6 mg/m2 . RESULTS: The most severe skin response, experienced by only six of the subjects, was limited to erythema without edema and could only be elicited by exposure to the highest light dose. Conversely, eight subjects had no discernible reaction to SSL at any light dose. For nearly all the patients, the peak skin response was obtained when the interval between sensitizer injection and exposure to SSL was 1 day and, generally, their sensitivity to SSL decreased with increasing sensitizer-light interval. For example, a 2-day sensitizer-SSL interval resulted in less severe reactions than those obtained with the 1-day interval in 79% of the subjects, while 90% of the subjects exposed to SSL 3 days after Photochlor infusion had responses that were less severe than those obtained with either the 1- or 2-day sensitizer-SSL interval. CONCLUSIONS: Photochlor, at clinically effective antitumor doses, causes only mild skin photosensitivity that declines rapidly over a few days. [source: Cancer Chemother Pharmacol. 2006 Jan;57(1):40-5. Epub 2005 Nov 5.] Photochlor is considered a second-generation photosensitizer because of its improved properties over Photofrin®. These two photosensitizers have closely related molecular structures but significantly different photophysical properties. Clinical studies have shown that Photochlor stays in the tumor for a long time and clears faster from the rest of the system and does not show any significant skin phototoxicity, a main drawback associated with most of the porphyrin-based compounds, including Photofrin. Photochlor also offers the advantage of long wavelength absorption that increases light penetration and minimizes the number of laser fibers needed to deliver light within the tumor. These properties are important for treating large and deep-seated tumors. [ soucre: Ravendra K. Pandey: Lighting Up the Lives of Cancer Patients by Developing Drugs for Tumor Imaging and Photodynamic Therapy:A “See and Treat” Approach, Oncology, 2008, 22-23]
| Biological target: | HPPH (Photochlor) is a second generation photosensitizer, which acts as a photodynamic therapy (PDT) agent. |
| In vitro activity: | Human esophageal squamous cell cancer (ESCC) is one of the most prevalent cancers in the world and ~250,000 ESCC cases are diagnosed each year in China, accounting for half of the world’s cases . However, the optimal treatment for squamous cell carcinoma of the esophagus remains unresolved.The present study investigated the effects of 2-(1-hexyloxyethyl)-2-devinylpyro pheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) on in vitro cell survival derived from human esophageal squamous cancer cells (Eca109). In order to evaluate the efficacy of HPPH- and Photofrin-mediated PDT in human ESCC cells, the Eca109 cells were incubated with various concentrations of HPPH (0.005–1 μg/ml) or Photofrin (0.5–15 μg/ml) for 24 h in the dark prior to being exposed to a laser light at 665 nm or 630 nm (20 mW/cm2, 2 J/cm2). The cells were then cultured for 48 h and the in vitro photosensitizing efficacy was determined using a CCK8 assay. A cell counting kit 8 (CCK8) assay was used to assess the phototoxicity of HPPH-mediated PDT in cultured Eca109 cells. The inhibition of tumor growth was determined by the changes in the relative tumor volume (RTV) and tumor weight. The results revealed that HPPH, in the range of 0.005–1 μg/ml, exhibited no cytotoxicity in the Eca109 cells without light exposure and that the in vitro efficiency of HPPH-mediated PDT was higher compared with that of Photofrin®-mediated PDT. In conclusion, the present study demonstrated that the phototoxicity of HPPH-mediated PDT is higher than that of Photofrin-mediated PDT of the same dose. HPPH possessed lower toxicity than Photofrin at the dose that achieved the same efficacy. Therefore, HPPH may be a promising agent for treating human esophageal squamous cell cancer (ESCC). Oncol Lett. 2013 Oct; 6(4): 1111–1119.Published online 2013 Jul 25. doi: 10.3892/ol.2013.1493 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796395/ |
| In vivo activity: | Photodynamic therapy (PDT) is known as a non-invasive treatment modality that is based on photochemical reactions between oxygen, photosensitizer, and a special wavelength of light. In this study, we evaluate several dose metrics, total fluence, photobleaching ratio, PDT dose, and mean reacted singlet oxygen (mean [1O2]rx) for predicting the PDT outcome and a clinically relevant tumor re-growth endpoint. For this reason, radiation-induced fibrosarcoma (RIF) mice tumors are treated with 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) and different in-air fluences (30 J/cm2, 50 J/cm2, 135 J/cm2, 250 J/cm2, and 350 J/cm2) and in-air fluence rates (20, 50, 75, 150 mW/cm2). The correlation of [1O2]rx with outcomes of 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated PDT is compared to fluence, photosensitizer photobleaching ratio, and PDT dose in a well-characterized mouse radiation-induced fibrosarcoma (RIF) tumor model. Tumors of about the same size treated with identical doses of HPPH and irradiated with the identical energy exhibited different surviving fractions as φair was lowered. Our results further suggest that tumors of about the same size treated with identical doses of HPPH and irradiated with the identical energy exhibited different surviving fractions as φ was increased. Therefore, φ effects must be considered as a possible source of treatment failure in PDT. J Biophotonics. 2016 Dec; 9(11-12): 1344–1354.Published online 2016 Sep 22. doi: 10.1002/jbio.201600121 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159301/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 3.0 | 4.70 |
The following data is based on the product molecular weight 636.82 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. Wu D, Liu Z, Fu Y, Zhang Y, Tang N, Wang Q, Tao L. Efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a in photodynamic therapy of human esophageal squamous cancer cells. Oncol Lett. 2013 Oct;6(4):1111-1119. doi: 10.3892/ol.2013.1493. Epub 2013 Jul 25. PMID: 24137473; PMCID: PMC3796395. 2. Luo D, Carter KA, Razi A, Geng J, Shao S, Lin C, Ortega J, Lovell JF. Porphyrin-phospholipid liposomes with tunable leakiness. J Control Release. 2015 Dec 28;220(Pt A):484-494. doi: 10.1016/j.jconrel.2015.11.011. Epub 2015 Nov 11. PMID: 26578438; PMCID: PMC4688124. 3. Grossman CE, Carter SL, Czupryna J, Wang L, Putt ME, Busch TM. Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity. Int J Mol Sci. 2016 Jan 14;17(1):101. doi: 10.3390/ijms17010101. PMID: 26784170; PMCID: PMC4730343. 4. Penjweini R, Kim MM, Liu B, Zhu TC. Evaluation of the 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) mediated photodynamic therapy by macroscopic singlet oxygen modeling. J Biophotonics. 2016 Dec;9(11-12):1344-1354. doi: 10.1002/jbio.201600121. Epub 2016 Sep 22. Erratum in: J Biophotonics. 2017 Mar;10 (3):473-474. PMID: 27653233; PMCID: PMC5159301. |
| In vitro protocol: | Wu D, Liu Z, Fu Y, Zhang Y, Tang N, Wang Q, Tao L. Efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a in photodynamic therapy of human esophageal squamous cancer cells. Oncol Lett. 2013 Oct;6(4):1111-1119. doi: 10.3892/ol.2013.1493. Epub 2013 Jul 25. PMID: 24137473; PMCID: PMC3796395. 2. Luo D, Carter KA, Razi A, Geng J, Shao S, Lin C, Ortega J, Lovell JF. Porphyrin-phospholipid liposomes with tunable leakiness. J Control Release. 2015 Dec 28;220(Pt A):484-494. doi: 10.1016/j.jconrel.2015.11.011. Epub 2015 Nov 11. PMID: 26578438; PMCID: PMC4688124. |
| In vivo protocol: | 1. Grossman CE, Carter SL, Czupryna J, Wang L, Putt ME, Busch TM. Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity. Int J Mol Sci. 2016 Jan 14;17(1):101. doi: 10.3390/ijms17010101. PMID: 26784170; PMCID: PMC4730343. 2. Penjweini R, Kim MM, Liu B, Zhu TC. Evaluation of the 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) mediated photodynamic therapy by macroscopic singlet oxygen modeling. J Biophotonics. 2016 Dec;9(11-12):1344-1354. doi: 10.1002/jbio.201600121. Epub 2016 Sep 22. Erratum in: J Biophotonics. 2017 Mar;10 (3):473-474. PMID: 27653233; PMCID: PMC5159301. |
1: Morales RDH, Hong Ong Y, Finlay J, Dimofte A, Simone CB, Friedberg JS, Busch TM, Cengel KA, Zhu TC. In vivo spectroscopic evaluation of human tissue optical properties and hemodynamics during HPPH-mediated photodynamic therapy of pleural malignancies. J Biomed Opt. 2022 Oct;27(10):105006. doi: 10.1117/1.JBO.27.10.105006. PMID: 36316298; PMCID: PMC9621284.
2: Mudambi S, Fitzgerald M, Pera P, Washington D, Chamberlain S, Fidrus E, Hegedűs C, Remenyik E, Shafirstein G, Bellnier D, Paragh G. KDM1A inhibition increases UVA toxicity and enhances photodynamic therapy efficacy. Photodermatol Photoimmunol Photomed. 2022 Aug 15. doi: 10.1111/phpp.12826. Epub ahead of print. PMID: 35968606.
3: Cheruku RR, Turowski SG, Durrani FA, Tabaczynski WA, Cacaccio J, Missert JR, Curtin L, Sexton S, Alberico R, Hendler CM, Spernyak JA, Grossman Z, Pandey RK. Tumor-Avid 3-(1'-Hexyloxy)ethyl-3-devinylpyrpyropheophorbide-a (HPPH)-3Gd(III)tetraxetan (DOTA) Conjugate Defines Primary Tumors and Metastases. J Med Chem. 2022 Jul 14;65(13):9267-9280. doi: 10.1021/acs.jmedchem.2c00547. Epub 2022 Jun 28. PMID: 35763292.
4: Ding Y, Yang R, Yu W, Hu C, Zhang Z, Liu D, An Y, Wang X, He C, Liu P, Tang Q, Chen D. Chitosan oligosaccharide decorated liposomes combined with TH302 for photodynamic therapy in triple negative breast cancer. J Nanobiotechnology. 2021 May 19;19(1):147. doi: 10.1186/s12951-021-00891-8. PMID: 34011362; PMCID: PMC8136194.
5: Wang H, Li J, Wang Z, Wang Y, Xu X, Gong X, Wang J, Zhang Z, Li Y. Tumor- permeated bioinspired theranostic nanovehicle remodels tumor immunosuppression for cancer therapy. Biomaterials. 2021 Feb;269:120609. doi: 10.1016/j.biomaterials.2020.120609. Epub 2020 Dec 18. PMID: 33378729.
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7: Borah BM, Cacaccio J, Durrani FA, Bshara W, Turowski SG, Spernyak JA, Pandey RK. Sonodynamic therapy in combination with photodynamic therapy shows enhanced long-term cure of brain tumor. Sci Rep. 2020 Dec 11;10(1):21791. doi: 10.1038/s41598-020-78153-0. PMID: 33311561; PMCID: PMC7732989.
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9: Hao Y, Chen Y, He X, Yu Y, Han R, Li Y, Yang C, Hu D, Qian Z. Polymeric Nanoparticles with ROS-Responsive Prodrug and Platinum Nanozyme for Enhanced Chemophotodynamic Therapy of Colon Cancer. Adv Sci (Weinh). 2020 Sep 6;7(20):2001853. doi: 10.1002/advs.202001853. PMID: 33101874; PMCID: PMC7578901.
10: Mo W, Patel NJ, Chen Y, Pandey R, Sunar U. Mapping fluorescence resonance energy transfer parameters of a bifunctional agent using time-domain fluorescence diffuse optical tomography. J Biophotonics. 2021 Jan;14(1):e202000291. doi: 10.1002/jbio.202000291. Epub 2020 Oct 22. PMID: 33025728.
11: Zhang S, Cheruku RR, Dukh M, Tabaczynski W, Patel NJ, White WH 3rd, Missert JR, Spernyak JA, Pandey RK. The Structures of Gd(III) Chelates Conjugated at the Periphery of 3-(1'-Hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) Have a Significant Impact on the Imaging and Therapy of Cancer. ChemMedChem. 2020 Nov 4;15(21):2058-2070. doi: 10.1002/cmdc.202000449. Epub 2020 Oct 14. PMID: 32916033; PMCID: PMC7722155.
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14: Borah BM, Cacaccio J, Watson R, Pandey RK. Phototriggered Release of Tumor- Imaging and Therapy Agents from Lyophilized Multifunctional Polyacrylamide Nanoparticles. ACS Appl Bio Mater. 2019 Dec 16;2(12):5663-5675. doi: 10.1021/acsabm.9b00741. Epub 2019 Nov 27. PMID: 35021560.
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16: Zhu TC, Ong Y, Kim MM, Liang X, Finlay JC, Dimofte A, Simone CB 2nd, Friedberg JS, Busch TM, Glatstein E, Cengel KA. Evaluation of Light Fluence Distribution Using an IR Navigation System for HPPH-mediated Pleural Photodynamic Therapy (pPDT). Photochem Photobiol. 2020 Mar;96(2):310-319. doi: 10.1111/php.13166. Epub 2019 Oct 22. PMID: 31556122; PMCID: PMC7093257.
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1. Yang W, Yoon Y, Lee Y, Oh H, Choi J, Shin S, Lee S, Lee H, Lee Y, Seo J. Photosensitizer-peptoid conjugates for photoinactivation of Gram-negative bacteria: structure-activity relationship and mechanistic studies. Org Biomol Chem. 2021 Jul 28;19(29):6546-6557. doi: 10.1039/d1ob00926e. PMID: 34259297.
