interesting thoughts and article links by slcimmun
Post# of 72440
Posted On: 12/23/2015 10:16:25 AM
interesting thoughts and article links by slcimmuno -- who granted permission to post it here:
I've been sold on B/HDP-Ms for a while. A good hedge against riskier K and P, not as far along. Would rather CTIX gets it right, everything lined up, than to rush things along. The formulation issues certainly delayed things too.
Anyway, leveraging the legwork of Polymedix, our ABXs stand a good-to-great chance of finally delivering on their potential.
Relatively new research (April 2015) out that references membrane-active antimicrobials, w/ a brief ref of Brilacidin. Interesting also the ref to their effect on cancer cells. Way back when I remember posting a bit on antimicrobial peptides (by extension, defensin mimetics) and their anti-cancer properties. So some more food for thought.
The researcher quoted, Verma, has even published on p53/MDM2, Nutlins, Stapled Peptides (i.e., Aileron)--obv a Bright Light with research interests that overlap w CTIX lead ABX/ONC products. He has co-published w /David Lane, a p53 Guru sans pareil.
Anyway, for the patient grasshopper, makes me think CTIX def playing in the right space w its lead antibiotic and cancer drug.
Looking forward to substantive developments in 2016.
EXCERPT
Membrane-active antimicrobials are expected to thwart this resistance by selectively penetrating and disrupting bacterial membranes, which are more difficult to reconfigure than proteins. However, the mechanism for this disruption remains unclear. A lack of general design principles has limited the development of membrane-active antimicrobials as a viable tool.
[...]
"A certain number of membrane-active antimicrobials currently in clinical trials, such as XF-73, LTX-109, and ***brilacidin,*** match our model," says Li. "This is quite exciting because it is the first reported instance of membrane-based fragment assembly," he adds.
The team is currently working on the development of antimicrobials that simultaneously target gram-positive and gram-negative pathogens. "We hope that the same concept can be extended to cancer cell membranes," says Verma.
http://m.phys.org/news/2015-12-antimicrobials...stant.html
ABSTRACT
http://www.sciencedirect.com/science/article/...via%3Dihub
//
Dr Chandra Verma Biography
http://www.bii.a-star.edu.sg/research/biography/chandra.php
SAMPLE PUBLICATIONS (129 in total)
ElSawy KM, Sim A, Lane DP, Verma CS, Caves LS. "A spatiotemporal characterization of the effect of p53 phosphorylation on its interaction with MDM2."
Cell Cycle. 2015 14:179-88.
Chee SM, Wongsantichon J, Soo Tng Q, Robinson R, Joseph TL, Verma C, Lane DP, Brown CJ, Ghadessy FJ.
"Structure of a stapled peptide antagonist bound to nutlin-resistant mdm2."
PLoS One. 2014 Aug 12;9:e104914.
Lau YH, de Andrade P, Sköld N, McKenzie GJ, Venkitaraman AR, Verma C, Lane DP, Spring DR.
"Investigating peptide sequence variations for 'double-click' stapled p53 peptides."
Org Biomol Chem. 2014 Jun 28;12(24):4074-7.
Sim AYL, Joseph T, Lane DP, Verma C.
"Mechanism of stapled peptide binding to MDM2: possible consequences for peptide design."
J Chem Theor Comput 2014, 10(4):1753-1761.
Hoe KK, Verma CS, Lane DP.
"Drugging the p53 pathway: understanding the route to clinical efficacy."
Nat Rev Drug Discov 13(3):217-236 (2014).
Lakshminarayanan R, Liu S, Li J, Nandhakumar M, Aung TT, Goh E, Jamie CYT, Saraswathi P, Tang C, Safie SRB, Lin LY, Riezman H, Zhou L, Verma CS, Beuerman RW.
"Synthetic Multivalent Antifungal Peptides Effective against Fungi."
PLoS One 9:e87730 (2014).
Lukman S, Lane DP, Verma CS.
"Mapping the Structural and Dynamical Features of Multiple p53 DNA Binding Domains: Insights into Loop 1 Intrinsic Dynamics."
PLoS One 8:e80221 (2013).
Wei SJ, Joseph T, Chee S, Li L, Yurlova L, Zolghadr K, Brown C, Lane D,Verma C, Ghadessy F.
"Inhibition of Nutlin-Resistant HDM2 Mutants by Stapled Peptides."
PLoS One 8:e81068 (2013) .
Elsawy KM, Verma CS, Lane DP, Caves LS.
"On the origin of the stereoselective affinity of Nutlin-3 geometrical isomers for the MDM2 protein."
CJ Brown, S Lain, CS Verma. AR Fersht, DP Lane.
"Awakening guardian angels: drugging the p53 pathway."
Nat Rev Cancer 9:862-873 (2009) (invited).
SG Dastidar, DP Lane, CS Verma.
"Modulation of p53 binding to MDM2: computational studies reveal important roles of Tyr100."
BMC Bioinformatics 15:S6 (2009).
A Madhumalar, HJ Lee, CJ Brown, DP Lane, CS Verma.
"Design of a novel MDM2 binding peptide based on the p53 family."
Cell Cycle 8:2828-36 (2009).
I've been sold on B/HDP-Ms for a while. A good hedge against riskier K and P, not as far along. Would rather CTIX gets it right, everything lined up, than to rush things along. The formulation issues certainly delayed things too.
Anyway, leveraging the legwork of Polymedix, our ABXs stand a good-to-great chance of finally delivering on their potential.
Relatively new research (April 2015) out that references membrane-active antimicrobials, w/ a brief ref of Brilacidin. Interesting also the ref to their effect on cancer cells. Way back when I remember posting a bit on antimicrobial peptides (by extension, defensin mimetics) and their anti-cancer properties. So some more food for thought.
The researcher quoted, Verma, has even published on p53/MDM2, Nutlins, Stapled Peptides (i.e., Aileron)--obv a Bright Light with research interests that overlap w CTIX lead ABX/ONC products. He has co-published w /David Lane, a p53 Guru sans pareil.
Anyway, for the patient grasshopper, makes me think CTIX def playing in the right space w its lead antibiotic and cancer drug.
Looking forward to substantive developments in 2016.
EXCERPT
Membrane-active antimicrobials are expected to thwart this resistance by selectively penetrating and disrupting bacterial membranes, which are more difficult to reconfigure than proteins. However, the mechanism for this disruption remains unclear. A lack of general design principles has limited the development of membrane-active antimicrobials as a viable tool.
[...]
"A certain number of membrane-active antimicrobials currently in clinical trials, such as XF-73, LTX-109, and ***brilacidin,*** match our model," says Li. "This is quite exciting because it is the first reported instance of membrane-based fragment assembly," he adds.
The team is currently working on the development of antimicrobials that simultaneously target gram-positive and gram-negative pathogens. "We hope that the same concept can be extended to cancer cell membranes," says Verma.
http://m.phys.org/news/2015-12-antimicrobials...stant.html
ABSTRACT
http://www.sciencedirect.com/science/article/...via%3Dihub
//
Dr Chandra Verma Biography
http://www.bii.a-star.edu.sg/research/biography/chandra.php
SAMPLE PUBLICATIONS (129 in total)
ElSawy KM, Sim A, Lane DP, Verma CS, Caves LS. "A spatiotemporal characterization of the effect of p53 phosphorylation on its interaction with MDM2."
Cell Cycle. 2015 14:179-88.
Chee SM, Wongsantichon J, Soo Tng Q, Robinson R, Joseph TL, Verma C, Lane DP, Brown CJ, Ghadessy FJ.
"Structure of a stapled peptide antagonist bound to nutlin-resistant mdm2."
PLoS One. 2014 Aug 12;9:e104914.
Lau YH, de Andrade P, Sköld N, McKenzie GJ, Venkitaraman AR, Verma C, Lane DP, Spring DR.
"Investigating peptide sequence variations for 'double-click' stapled p53 peptides."
Org Biomol Chem. 2014 Jun 28;12(24):4074-7.
Sim AYL, Joseph T, Lane DP, Verma C.
"Mechanism of stapled peptide binding to MDM2: possible consequences for peptide design."
J Chem Theor Comput 2014, 10(4):1753-1761.
Hoe KK, Verma CS, Lane DP.
"Drugging the p53 pathway: understanding the route to clinical efficacy."
Nat Rev Drug Discov 13(3):217-236 (2014).
Lakshminarayanan R, Liu S, Li J, Nandhakumar M, Aung TT, Goh E, Jamie CYT, Saraswathi P, Tang C, Safie SRB, Lin LY, Riezman H, Zhou L, Verma CS, Beuerman RW.
"Synthetic Multivalent Antifungal Peptides Effective against Fungi."
PLoS One 9:e87730 (2014).
Lukman S, Lane DP, Verma CS.
"Mapping the Structural and Dynamical Features of Multiple p53 DNA Binding Domains: Insights into Loop 1 Intrinsic Dynamics."
PLoS One 8:e80221 (2013).
Wei SJ, Joseph T, Chee S, Li L, Yurlova L, Zolghadr K, Brown C, Lane D,Verma C, Ghadessy F.
"Inhibition of Nutlin-Resistant HDM2 Mutants by Stapled Peptides."
PLoS One 8:e81068 (2013) .
Elsawy KM, Verma CS, Lane DP, Caves LS.
"On the origin of the stereoselective affinity of Nutlin-3 geometrical isomers for the MDM2 protein."
CJ Brown, S Lain, CS Verma. AR Fersht, DP Lane.
"Awakening guardian angels: drugging the p53 pathway."
Nat Rev Cancer 9:862-873 (2009) (invited).
SG Dastidar, DP Lane, CS Verma.
"Modulation of p53 binding to MDM2: computational studies reveal important roles of Tyr100."
BMC Bioinformatics 15:S6 (2009).
A Madhumalar, HJ Lee, CJ Brown, DP Lane, CS Verma.
"Design of a novel MDM2 binding peptide based on the p53 family."
Cell Cycle 8:2828-36 (2009).
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