Inhibitors of Rb Phosphorylation
Hit-to-Lead
A potent hit-to-lead compound series which inhibit phosphorylation of the retinoblastoma (Rb) protein have been identified from a cellular assay. Rb acts as a tumour suppressor protein in its unphosphorylated form. Therefore these compounds have promising potential as anticancer agents. Work to deconvolute the biochemical target of these compounds is ongoing and CRT is now seeking a commercial partner interested in pursuing a co-development or licensing arrangement to further develop this programme.
Contact: Dr Laura Fletcher, lfletcher@CancerTechnology.com
Potent Inhibitors of Platinum Resistant Cancers (New)
Hit-to-Lead
Defective mismatch DNA repair (MMR) is observed in a variety of tumour types and is known to be associated with resistance to chemotherapy.A series of compounds showing increased activity in MMR deficient versus MMR proficient cells has been developed. The lead compound is highly potent in vitro (low nM activity) in a range of tumour cells and inhibits the growth of human tumour xenografts in vivo after single bolus injections. CRT is now seeking a commercial partner interested in licensing this opportunity to further progress this programme.
Contact: Dr Anne Horgan, ahorgan@CancerTechnology.com
 Further details can be accessed here
Axl Kinase Inhibitors
CRT Discovery Laboratories Project
Hit-to-Lead - Lead Optimisation
Axl kinase is a receptor tyrosine kinase which is over-expressed in a number of solid tumours. The kinase is oncogenic and is involved in cell invasion, migration, angiogenesis and also has pro-survival activities. Knock-down of Axl in human breast cancer tumour cells inhibits xenograft growth in vivo. Hit-to-lead stage compound series with low nM IC50 activities have been developed. CRT is now seeking a commercial partner to co-develop and further progress this programme.
Contact: Dr Theo Balasas, tbalasas@CancerTechnology.com
Further details can be accessed here
Protein Kinase C iota (PKCι)
CRT Discovery Laboratories Project
Hit-to-Lead - Lead Optimisation
Protein kinase C (PKC) is a multigene family of lipid-regulated protein serine/threonine kinases which exhibit distinct tissue distribution and play key roles in regulating cell proliferation, differentiation and survival. PKCι has been reported to be an oncogene in the major (80%) subtype of lung cancer, non-small cell lung cancer (NSCLC). Compelling evidence has emerged which strongly implicates inhibition of PKCι as a direct target for an antitumour agent against NSCLC and several other common tumours, namely colon, ovarian, glioblastoma and CML. CRT has developed and validated a fluorescence polarisation assay for PKCι activity which has been used for high throughput screening (HTS) of a diverse compound library. Compounds from this HTS have been validated as potent inhibitors of this enzyme and fall into a number of distinct hit to lead chemical series. Mechanism of action studies have demonstrated one series to be non competitive ATP inhibitors and the second series to be ATP competitive inhibitors.
Contact: Dr Phil Masterson, pmasterson@CancerTechnology.com
Further details can be accessed here
PIP5 Kinase Inhibitors
CRT Discovery Laboratories Project
Hit-to-Lead - Lead Optimisation
Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) are responsible for phosphatidylinositol-4,5-bisphosphate (PIP2) production. PIP2 plays a pivotal role in cytoskeletal organisation, cell proliferation, survival and apoptosis. Inhibition of PIP5K leads to anti-proliferative and pro-apoptotic responses. Hit-to-lead stage compound series with low nM IC50 activities have been developed. Associated with the programme is novel IP and a patented biochemical assay. CRT is now seeking a commercial partner interested in pursuing a co-development arrangement to further progress this programme.
Contact: Dr Nick Gower, ngower@CancerTechnology.com
Further details can be accessed here
Inhibitors of the MDM2-p53 Protein-Protein Interaction
Lead Optimisation
A novel series of potent MDM2-p53 inhibitors that display a cellular response consistent with the activation of p53. Significant SAR has been generated around the isoindolinone scaffold with structural data available. CRT is now seeking a commercial partner interested in collaborating with the academic groups to further progress this programme..
Contact: Dr Phil Elstob, pelstob@CancerTechnology.com
Further details can be accessed here
Chk2 Inhibitor Programme
Lead Optimisation
Two novel compound series with sub 1 µM activity against the Chk2 cell-cycle checkpoint kinase have been developed. This programme currently comprises novel IP, established biological assays and co-crystallographic methods to support and inform ongoing medicinal chemistry. CRT is now seeking a commercial partner interested in pursuing a co-development arrangement to further progress this programme
Contact: Dr Laura Fletcher, lfletcher@CancerTechnology.com
Further details can be accessed here
Novel Histone Deacetylase (HDAC) Inhibitors (New)
Lead Optimisation
Highly selective and potent HDAC compounds have been developed. World-wide rights to the patented compounds are available for licensing.
Contact: Dr Elisabeth Parker, eparker@CancerTechnology.com
Chk1 Inhibitor Programme
Lead Optimisation - Proof-of-Principle
Novel compound series with nM activity against the Chk1 cell-cycle checkpoint kinase have been identified starting from a combined crystallographic-bioassay template screen. The lead series demonstrates Chk1 cellular activity, has good ADMET properties, and has been subject to ongoing medicinal chemistry to optimise cellular and in vivo activity. The programme also comprises novel IP, established biological assays and co-crystallographic expertise. CRT is now offering prospective commercial partners global rights to the Chk1 programme on an exclusive basis for all fields.
Contact: Dr Phil Masterson, pmasterson@CancerTechnology.com
Further details can be accessed here
Protein Kinase D (PKD)
CRT Discovery Laboratories Project
In Vivo Proof-of-Principle
Members of the protein kinase D family have been shown to play an integral part in signalling cascades that are aberrantly activated during a number of pathological conditions including cancer, angiogenesis and cardiac hypertrophy. Two series of potent and selective inhibitors of PKD have been developed. The compounds have potent activity in cell based assays with the lead series exhibiting oral bioavailability and in vivo efficacy in xenograft models. CRT is seeking commercial partners for late stage pre-clinical and clinical development of these compounds.
Contact: Dr Raj Mehta, rmehta@CancerTechnology.com
Further details can be accessed here
Hypoxic Response Inhibitors
In Vivo Proof-of-Principle
Novel derivatives of ketoglutarate have been developed and demonstrated to reduce HIF-1 alpha levels in cells under hypoxic conditions. In vivo proof-of-concept efficacy demonstrated with protoype compounds. The compounds may also be applicable to the treatment of cancers in patients predisposed to neoplasia through mutations within the Krebs tricarboxylic acid cycle (TCA cycle).
Contact: Dr Adele Casamassima, acasamassima@CancerTechnology.com
Further details can be accessed here
Novel Photosentisiser - Nanoparticle Conjugates
In Vivo Proof-of-Principle
A novel photosensitiser technology based on a functionalised gold-nanoparticle delivery vehicle that incorporates novel phthalocyanine photosensitisers has been developed for application in therapeutic and related fields. The technology delivers enhanced levels of the cytotoxic species, singlet oxygen. In vivo proof of concept studies, in the field of oncology, are in progress.
Contact: Dr Theo Balasas, tbalasas@CancerTechnology.com
Further details can be accessed here
Fenretinide US and EU Orphan Designations
Clinical Phase I
Orphan designations for this retinamide have been secured in Ewing’s sarcoma family of tumours (US), malignant bone tumours (EU) and soft tissue sarcomas (EU). Pre-clinical data in animal models shows that fenretinide is effective at delaying tumour growth, and phase I clinical data show that fenretinide is well tolerated with manageable toxicities and that the required in vitro concentrations are achievable in the plasma. A phase II trial is being planned and an option to the data from this trial is available.
Contact: Dr Elisabeth Parker, eparker@CancerTechnology.com
Further details can be accessed here
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