Inhibitors of LIMK1 and LIMK2 (New)
Licensing or Collaboration
Hit-to-Lead/Lead Optimisation
LIMK1 and LIMK2 are emerging targets for both cancer and ocular disease. They are up-regulated in metastatic breast and prostate tumours. Over-expression has been demonstrated to increase tumour cell migration and invasion and to increase tumour growth, angiogenesis and metastasis in vivo. Conversely, abrogation of LIMK function results in decreased breast cancer cell motility and formation of osteolytic bone lesions in an animal model of invasion. Down-regulation of LIMK1 has been demonstrated to reduce inflammation in a mouse model of ocular surgery and small molecule inhibition or genetic deletion of LIMK2 is effective in reducing intraocular pressure in mouse models, a key risk factor in disease progression in glaucoma. CRT has developed two series of novel, potent, ATP-competitive small molecule inhibitors of LIMK1/2 which (i) inhibit the ability of cancer cells to invade in multiple authentic cancer cell invasion assays, and (ii) sensitise tumour cells to cell death induced by chemotherapeutic agents.
CRT is now seeking a commercial partner to progress these exciting compounds under a licensing or co-development model.
Contact: Dr Laura Fletcher, lfletcher@CancerTechnology.com
 Further details can be accessed here
Senectus Therapeutics Limited (New)
Investment or Collaboration
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 Anthony Brown, abrown@CancerTechnology.com
Further details can be accessed here
Novel Radiolabelled Bisphosphonates
In Vivo Proof-of-Principle
Bone metastases are a major problem in many of the largest cancer indications and improved imaging agents or treatments for such patient groups would represent a significant market. We have developed and patented novel compounds which may overcome the clinical limitations associated with currently used radiolabelled bisphosphonates and increase their utility in both the imaging and therapeutic contexts. These novel compounds have simple and efficient synthesis routes and provide a means to overcome the poor stability and sub-optimal biodistribution of current agents. We are seeking a licensee to undertake further development of these compounds and clinical testing in imaging and/or therapeutic contexts under a licensing or collaborative relationship.
Contact: Dr Angus Lauder, alauder@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
Chk1 is a serine/threonine kinase that is phosphorylated and activated in response to DNA damage, initiating a signalling cascade culminating in cell cycle arrest in the S and G2/M phases. Inhibition of Chk1 has been shown to abrogate cell cycle arrest leading to enhanced tumour cell death following DNA damage by a range of chemotherapeutics. Chk1 inhibitors are anticipated to provide a therapeutic strategy for enhancing the effectiveness of the genotoxic agents currently used in cancer treatment. ATP-competitive inhibitors exhibiting low nM activity against Chk1 have been developed. Optimised compounds have potent activity in cell-based assays, with the Lead Series exhibiting efficacy in vivo in combination with irinotecan and gemcitabine in human colon cancer xenografts. 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
Novel Photosentisiser - Nanoparticle Conjugates
In Vivo Proof-of-Principle
A novel gold nanoparticle-photosensitiser conjugate technology has been developed for application in therapeutic and related fields. In vivo proof of principle studies show that administration of the nanoparticle conjugates results in increased inhibition of tumour growth over both free photosensitiser and currently marketed PDT products. The conjugates also exhibit excellent photo and general toxicity profiles. CRT is seeking a commercial licensing or collaborative development partner.
Contact: Dr Theo Balasas, tbalasas@CancerTechnology.com
Further details can be accessed here
Atypical Protein Kinase C (aPKC)
CRT Discovery Laboratories Project
Lead Optimisation
PKCi and PKCz together define the atypical sub-class of the Protein Kinase C (aPKC) family. They have been implicated in diverse cellular processes including regulation of cell polarity, and the control of cellular migration and growth. Recent clinical and genetic evidence has suggested that the aPKCs play a key role in driving tumourigenesis. Inhibitors of aPKC are anticipated to act as direct anti-proliferative, anti-metastatic and chemopotentiating agents in tumours driven by high levels of aPKC expression and activity. Two series of ATP-competitive inhibitors exhibiting low nM activity against aPKCs have been developed. In phenotypic assays, aPKC inhibition leads to i) a pronounced decrease in proliferation of NSCLC and ovarian cancer cells, and ii) blocks the anchorage independent growth of NSCLC cell lines. CRT is now seeking a commercial partner for this first-in-class Lead Optimisation programme.
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. These potent compounds are effective in cellular models and show good in vivo pharmacokinetic properties. 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
Chk2 Inhibitor Programme
Lead Optimisation
A potent and selective compound series with low nM activity against the Chk2 cell-cycle checkpoint kinase has been developed. This programme currently comprises novel patented compounds, established biological assays, co-crystallographic methods to support and inform ongoing medicinal chemistry and novel synergy studies. CRT is now seeking a commercial partner interested in pursuing a co-development or direct licensing arrangement.
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 Tanya Moore, tmoore@CancerTechnology.com
Novel Inhibitors of Aurora Kinase
Lead Optimisation
A potent series of compounds with low nM activity against Aurora-A and Aurora-B has been discovered. Compounds from this series have demonstrated good cellular activity and oral in vivo activity in colon and ovarian tumour xenografts. On-going medicinal chemistry efforts are focusing on optimising PK properties whilst maintaining potency and cell based activity. The programme also comprises novel IP including a patented lead series, established biological assays, cellular and in vivo PD biomarkers and on-going studies to identify patient populations most likely to respond to Aurora inhibition. In addition, a crystallography 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. CRT is now seeking a commercial partner to further progress the pan-Aurora and/or the Aurora-A selective programmes.
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 Surbhi Gupta, sgupta@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 Tanya Moore, tmoore@CancerTechnology.com
Further details can be accessed here
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 Roisin NicAmhlaoibh, rnicamhlaoibh@CancerTechnology.com
Further details can be accessed here
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