ADPM06

WARNING: This product is for research use only, not for human or veterinary use.

Description:ADPM06 is an emerging non-porphyrin PDT agent which has been specifically designed for therapeutic application. It was demonstrated that ADPM06-PDT was well tolerated in vivo and elicited impressive complete response rates in various models of cancer when a short drug-light interval was applied. Using a drug and light combination that reduced the clonogenicity of MDA-MB-231 cells by >90%. PDT-induced apoptosis was also found to be independent of p53 tumor suppressor status. A robust therapeutic response in vivo was demonstrated, with a substantial reduction in tumor proliferation observed, as well as a rapid induction of apoptosis and initiation of ER stress, mirroring numerous aspects of the mechanism of action of ADPM06 in vitro. Finally, using a combination of (18) F-labeled 3'-deoxy-3'-fluorothymidine ((18) F-FLT) nuclear and optical imaging, a considerable decrease in tumor proliferation over 24-hr in two models of human cancer was observed. Taken together, this data clearly establishes ADPM06 as an exciting novel PDT agent with significant potential for further translational development. (source: Int J Cancer. 2012 Feb 1;130(3):705-15 ).

Price and Availability

ADPM06, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 200090Name: ADPM06CAS#: 490035-90-0Chemical Formula: C34H24BBr2F2N3O2Exact Mass: 713.02964Molecular Weight: 715.19Elemental Analysis:C, 57.10; H, 3.38; B, 1.51; Br, 22.34; F, 5.31; N, 5.88; O, 4.47

Synonym:Azadipyrromethane ADPM06; ADPM 06; ADPM-06.

IUPAC/Chemical Name:2,8-dibromo-5,5-difluoro-3,7-bis(4-methoxyphenyl)-1,9-diphenyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,5,2]triazaborinin-4-ium-5-uide.

InChi Key:YVKIKMDAXWFEJI-UHFFFAOYSA-N

InChi Code:InChI=1S/C34H24BBr2F2N3O2/c1-43-25-17-13-23(14-18-25)31-29(36)27(21-9-5-3-6-10-21)33-40-34-28(22-11-7-4-8-12-22)30(37)32(42(34)35(38,39)41(31)33)24-15-19-26(44-2)20-16-24/h3-20H,1-2H3

SMILES Code:COC1=CC=C(C2=C(Br)C(C3=CC=CC=C3)=C(N2[B-]4(F)F)N=C5[N+]4=C(C6=CC=C(OC)C=C6)C(Br)=C5C7=CC=CC=C7)C=C1

Technical Data

Additional Information

ADPM06 is a totally new class of nonporphyrin photodynamic therapeutic agent.  Confocal laser scanning microscopy imaging showed that this compound is exclusively localised to the cytosolic compartment, with specific accumulation in the endoplasmic reticulum and to a lesser extent in the mitochondria. Light-induced toxicity assays, carried out over a broad range of human tumour cell lines, displayed EC50 values in the nano-molar range for ADPM06, with no discernable activity bias for a specific cell type. Strikingly, the more active agent, ADPM06, even retained significant activity under hypoxic conditions. This photosensitiser showed low to nondeterminable dark toxicity. Flow cytometric analysis revealed that ADPM06 is highly effective at inducing apoptosis as a mode of cell death. The photophysical and biological characteristics of these PDT agents suggest that they have potential for the development of new anticancer therapeutic [source: Br J Cancer. 2005 May 9;92(9):1702-10.]  A recent in vivo study, using a multi-modality imaging approach to assess efficacy of treatment as well as probe the mechanism of action of ADPM06-mediated PDT, showed that tumor ablation in 71% of animals bearing mammary tumors was achieved after delivery of 2 mg/kg-1 of ADPM06 followed immediately by light irradn. with 150 J/cm-2. The inherent fluorescence of ADPM06 was utilized to monitor organ biodistribution patterns, with fluorescence reaching baseline levels in all organs within 24 h. Mechanism of action studies were carried out using dynamic positron emission tomog. and magnetic resonance imaging techniques, which, when taken together, indicated a decrease in tumor vascular perfusion and concomitant redn. in tumor metab. over time after treatment. The encouraging treatment responses in vivo and vascular-targeting mechanism of action continue to indicate therapeutic benefit for this new class of photosensitizer. [source: British Journal of Cancer (2009), 101(9), 1565-1573.]    

References

 1: O"Connor AE, McGee MM, Likar Y, Ponomarev V,Callanan JJ, O"shea DF, Byrne AT, Gallagher WM. Mechanism of cell deathmediated by a BF(2) -chelated tetraryl-azadipyrromethene photodynamictherapeutic: Dissection of the apoptotic pathway in vitro and in vivo.Int J Cancer. 2011 Mar 16. doi: 10.1002/ijc.26073. [Epub ahead of print]PubMed PMID: 21413012.

2: Flavin K, Lawrence K, Bartelmess J, Tasior M, Navio C, Bittencourt C,O"Shea DF, Guldi DM, Giordani S. Synthesis and characterization of boronazadipyrromethene single-wall carbon nanotube electron donor-acceptorconjugates. ACS Nano. 2011 Feb 22;5(2):1198-206. Epub 2011 Feb 3. PubMedPMID: 21291283.

3: Byrne AT, O"Connor AE, Hall M, Murtagh J, O"Neill K, Curran KM,Mongrain K, Rousseau JA, Lecomte R, McGee S, Callanan JJ, O"Shea DF,Gallagher WM. Vascular-targeted photodynamic therapy with BF2-chelatedTetraaryl-Azadipyrromethene agents: a multi-modality molecular imagingapproach to therapeutic assessment. Br J Cancer. 2009 Nov3;101(9):1565-73. Epub 2009 Oct 13. PubMed PMID: 19826417; PubMedCentral PMCID: PMC2778519.

4: Teets TS, Updegraff JB, Esswein AJ, Gray TG. Three-coordinate,phosphine-ligated azadipyrromethene complexes of univalent group 11metals. Inorg Chem. 2009 Sep 7;48(17):8134-44. PubMed PMID: 19655715.

5: Loudet A, Bandichhor R, Wu L, Burgess K. Functionalized BF(2)Chelated Azadipyrromethene Dyes. Tetrahedron. 2008 Apr21;64(17):3642-3654. PubMed PMID: 19458781; PubMed Central PMCID:PMC2390871.

6: Teets TS, Partyka DV, Updegraff JB 3rd, Gray TG. Homoleptic,four-coordinate azadipyrromethene complexes of d10 zinc and mercury.Inorg Chem. 2008 Apr 7;47(7):2338-46. Epub 2008 Feb 27. PubMed PMID:18311885.

7: Teets TS, Partyka DV, Esswein AJ, Updegraff JB 3rd, Zeller M, HunterAD, Gray TG. Luminescent, three-coordinate azadipyrromethene complexesof d(10) copper, silver, and gold. Inorg Chem. 2007 Aug6;46(16):6218-20. Epub 2007 Jul 14. PubMed PMID: 17630731.

8: Killoran J, O"Shea DF. Impact of a conformationally restrictedreceptor on the BF2 chelated azadipyrromethene fluorosensing platform.Chem Commun (Camb). 2006 Apr 14;(14):1503-5. Epub 2006 Feb 27. PubMedPMID: 16575441.

9: Hall MJ, Allen LT, O"Shea DF. PET modulated fluorescent sensing fromthe BF2 chelated azadipyrromethene platform. Org Biomol Chem. 2006 Mar7;4(5):776-80. Epub 2006 Jan 19. PubMed PMID: 16493459.