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 Andrea Schievella, aschievella@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-principle studies show increased inhibition of tumour growth in comparison to currently marketed photosensitisers.
Contact: Dr Lilian Hook, lhook@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 optimised compounds have potent activity in cell based assays with the lead series exhibiting oral bioavailability and in vivo efficacy in xenograft models. CRT is now seeking a commercial partner for this first-in-class pre-clinical and clinical development programme.
Contact: Dr Raj Mehta, rmehta@CancerTechnology.com
Further details can be accessed here
Chk1 Inhibitor Programme
In Vivo - 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
Atypical Protein Kinase C (aPKC)
CRT Discovery Laboratories Project
Lead Optimisation
Protein Kinase C (PKC) is a family of at least 12 serine/threonine kinases that have been divided into three structurally and functionally distinct enzyme classes – the classic PKCs, novel PKCs, and atypical PKCs (aPKCs; PKCζ and PKCι). Recent clinical and genetic evidence has suggested that the aPKCs play a key role in tumourigenesis. For instance, PKCι has been identified as an oncogene in non-small cell lung cancer (NSCLC), and its transgenic overexpression in the colon is permissive for carcinogen-induced colon carcinogenesis. PKCζ has been described as a target for Rituximab treatment in follicular lymphoma, and its inhibition has been shown to sensitise cancer cells to a number of commonly used chemotherapeutic agents. This and other data strongly implicates inhibition of the aPKCs isoenzymes as a novel target for an anti-tumour therapeutic. Following a major industrial style drug discovery campaign, compounds from a HTS have been validated as potent inhibitors of this enzyme and fall into a number of distinct novel ATP competitive chemical series. Inhibitors demonstrate good selectivity against a broad panel of kinases, are highly selective against the classic and novel PKCs and display promising early in vitro ADME properties. In cell-based assays PKCι inhibitors show biomarker modulation in the sub-micromolar range in NSCLC lines, and are potent inhibitors of anchorage-independent tumour cell growth.
Contact: Dr Phil Masterson, pmasterson@CancerTechnology.com
Further details can be accessed here
PIP5 Kinase Inhibitors
CRT Discovery Laboratories Project
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. Lead Optimisation 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 Roisin NicAmhlaoibh, rnicamhlaoibh@CancerTechnology.com
Further details can be accessed here
Novel Bisphosphonates with Enhanced Anti-cancer Activity (New)
Lead Optimisation
Bisphosphonates are used extensively to treat osteoporosis and hypercalcemia due to malignancy; in addition, they have potent effects on tumor cell proliferation, invasiveness and angiogenesis, and they activate gd T cells to kill tumor cells. This has led to considerable interest in expanding their use as direct anti-cancer agents, with recent clinical trial results in breast and hormone refractory prostate cancer showing considerable promise. The invention here centers around the identification of novel, highly lipophilic bisphosphonates with increased anti-cancer activity, due to inhibition of multiple signaling pathways, combined with immune system activation.
Contact: Dr Larry Steranka, lsteranka@CancerTechnology.com
Further details can be accessed here
Chk2 Inhibitor Programme
Lead Optimisation
Two potent and selective compound series with low nM 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 or direct licensing arrangement to further progress this programme.
Contact: Dr Laura Fletcher, lfletcher@CancerTechnology.com
Further details can be accessed here
CYP26 Inhibitor Programme (New)
Lead Optimisation
CYP26, a cytochrome P450 enzyme, is induced in response to retinoic acid treatment and provides the main route for metabolism of all-trans retinoic acid (ATRA). The initially impressive therapeutic effects of ATRA and its isomer (13-cis retinoic acid) are undermined by CYP-26-mediated resistance. A series of potent and selective CYP26 inhibitors has been developed and CRT is seeking a commercial partner interested in pursuing a co-development and/or licensing arrangement to further progress this programme.
Contact: Dr Phil Elstob, pelstob@CancerTechnology.com
Novel Inhibitors of Aurora Kinase (New)
Lead Optimisation
A novel potent series of compounds with low nM activity against Aurora-A and Aurora-B has been discovered. Development candidates, pertaining to two sub-series, are being selected based upon in vivo efficacy and overall compound profile. Aurora kinases are involved in the control of the centrosome maturation and cytokinesis; their over-expression has been observed in a variety of tumour types and is often associated with genetic instability and poor prognosis. Compounds from the most advanced chemical sub-series have demonstrated cellular activity, good oral ADME properties and oral in vivo activity in colon and ovarian human tumour xenografts. The programme also comprises novel IP including a patented lead series, established biological assays, cellular and in vivo PD biomarkers and on-going efforts to identify patient populations most likely to respond to Aurora inhibition. In addition, an X-ray crystal structure driven programme focusing on Aurora-A selective inhibitors has been initiated. This programme has identified lead compounds with cellular selectivity (>50 fold) for Aurora A versus Aurora B.
Contact: Dr Anne Horgan, ahorgan@CancerTechnology.com
Further details can be accessed here
Novel Histone Deacetylase (HDAC) Inhibitors
Lead Optimisation
Novel, highly selective HDAC inhibitors have been developed and in silico techniques continue to support these compounds through lead optimisation. The compounds possess sub--micromolar potency against key isoforms and display a desirable in vitro ADME profile. Promising activity has been demonstrated in several subsets of NCI's tumour cell panel. World-wide rights to the patented compounds are available for licensing.
Contact: Dr Chris Lowe, clowe@CancerTechnology.com
Inhibitors of the MDM2-p53 Protein-Protein Interaction
Hit-to-Lead/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 and structural data is available from an ongoing academic collaboration. The compounds are the subject of three filed patent applications. 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
Inhibitors of Rb Phosphorylation
Hit-to-Lead
A potent hit-to-lead compound series which inhibits phosphorylation of the retinoblastoma (Rb) protein and inactivates eIF-2a has 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
Axl Kinase Inhibitors
CRT Discovery Laboratories Project
Hit-to-Lead
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
Hypoxic Response Inhibitors
Hit-to-Lead
Novel derivatives of ketoglutarate have been developed and demonstrated to reduce HIF-1 alpha levels in cells under hypoxic conditions. In vivo proof-of-principle 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 Joanne Graham, jgraham@CancerTechnology.com
Further details can be accessed here
Senectus Therapeutics Limited (New)
Assay Development & Early Screening
Senectus Therapeutics Ltd is a CRT led company focused on understanding and then drugging cellular senescence. Senectus is founded on a hand-picked consortium of key UK scientists and their rapidly advancing understanding of cellular senescence in cancer biology. In conceiving Senectus, the primary objective was to bring together world leading CRUK expertise in mammalian cellular senescence along with new and advanced technologies in cell engineering and imaging to generate an improved understanding of senescence, a toolbox of high content screening techniques, reagents and tools. Ultimately, the outcome of the initiative will be identification of critical paths in cellular senescence, development of screens for compounds modulating senescence and small molecules and target leads for drug development and pathway manipulation.
Senectus has secured $1M in seed funding and is currently seeking further investment. Further financing could take the form of equity or programme-specific collaborative investment.
Contact: Dr Sarah Molton, smolton@CancerTechnology.com
Further details can be accessed here
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