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Hemic and Lymphatic Diseases

Neoplasms

Urogenital Diseases

Small molecule drug

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Disease Domain	Count

Hemic and Lymphatic Diseases	1
Neoplasms	1

Top 5 Drug Type	Count

Small molecule drug	1

Top 5 Target	Count

G4(G-Quadruplex)	1

This is a Phase 2, open-label, multicenter, efficacy and safety study of quarfloxin in patients with low or intermediate grade neuroendocrine cancer. The purpose of this study is to evaluate the rate of clinical benefit response to quarfloxin treatment including the reduction in secretory symptoms of flushing and/or diarrhea or the reduction quantifiable hormones or other biochemical tumor markers.

Start Date01 Oct 2008

Sponsor / Collaborator

Cylene Pharmaceuticals, Inc.

100 Clinical Results associated with Cylene Pharmaceuticals, Inc.

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0 Patents (Medical) associated with Cylene Pharmaceuticals, Inc.

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30

Literatures (Medical) associated with Cylene Pharmaceuticals, Inc.

01 Oct 2014·Cancer Research

Abstract 2687: CK2 inhibitor CX-4945 modulates AKT, NF-kB, TP53 and MEK inhibitor PD-325901 targets AP1 mediated CK2 inhibitor drug resistance in head and neck cancer

Author: Chen, Zhong ; Friedman, Jay ; Anderes, Kenna ; Waes, Carter Van ; Kannabiran, Vishnu ; Mohan, Suresh ; Bian, Yansong ; Han, Jiawei

AbstractWe previously identified upregulated kinase CK2 as an activator of NF-B and repressor of TP53 in promoting the malignant phenotype of head and neck squamous cell carcinoma (HNSCC). Here, we investigate the anti-tumor effects of a small molecule CK2 inhibitor CX-4945, alone and in combination with MEK inhibitor PD-0325901 (PD-901), in human HNSCC models in vitro and in vivo. CX-4945 IC50s ranged from 3.4 µM to 11.9 µM in 9 UMSCC cell lines. CX-4945 caused S and G2/M cell cycle arrest, and induced sub-G0 DNA fragments, indicating cell death. CX-4945 inhibited NF-B and BcL-XL prosurvival reporter genes in wild type (wt) TP53 (UMSCC1) and mutant (mt) TP53 (UMSCC46) cell lines, and concurrently upregulated proapoptotic TP53, p21 and prosurvival AP-1 activity only in the wtTP53 cell line. Correspondingly, CK2 phosphorylation of AKT S129 as well as T308 and S473 prosurvival signaling was reduced in both cell lines, but AP-1 inducing p-Erk1/2Thr202/204 was increased in the wtTP53 cell line. In the UMSCC1 xenografts, CX-4945 treatment significantly decreased PI3K/Akt/mTOR pathway signaling by immunostaining. While CX-4945 increased TP53 and TUNEL apoptosis marker staining at early time points (13 days after CX4945 treatment), an opposing increase in p-Erk, FosL1, cJun, JunB, and proliferation (Ki67) were also observed. Consistent with these opposing effects, no significant tumor reduction or improvement in survival was observed by CX-4945 alone. However, combination of CX-4945 with MEK/ERK inhibitor PD-901 exhibited significant synergistic anti-proliferative effects in vitro. Significant anti-tumor effects were observed with MEK inhibitor alone and in combination with CX-4945 in vivo, further supporting a role for MEK/ERK/AP-1 in resistance to CX-4945 in this HNSCC model.Supported by NIH Medical Research Scholars Program and NIDCD intramural projects ZIA-DC-000016, 73 and 74.Citation Format: Yansong Bian, Jiawei Han, Vishnu Kannabiran, Suresh Mohan, Jay Friedman, Kenna Anderes, Zhong Chen, Carter Van Waes. CK2 inhibitor CX-4945 modulates AKT, NF-kB, TP53 and MEK inhibitor PD-325901 targets AP1 mediated CK2 inhibitor drug resistance in head and neck cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2687. doi:10.1158/1538-7445.AM2014-2687

01 Jan 2014·LeukemiaQ1 · MEDICINE

Activity of the clinical-stage CK2-specific inhibitor CX-4945 against chronic lymphocytic leukemia

Q1 · MEDICINE

Letter

Author: Drygin, D ; Silva, M G ; Cardoso, B A ; Martins, L R ; Ghia, P ; Stansfield, R ; Antunes, I ; Barata, J T ; Bertilaccio, M T S ; Lúcio, P ; Melão, A

Activity of the clin.-stage CK2-specific inhibitor CX-4945 against chronic lymphocytic leukemia.

15 Apr 2013·Cancer Research

Abstract 4355: Inhibition of RNA Polymerase I as a strategy to treat cancer.

Author: Hannan, Katherine M. ; Pearson, Richard B. ; Bywater, Megan J. ; Johnstone, Ricky W. ; Drygin, Denis ; McArthur, Grant A. ; Von Hoff, Daniel ; Hannan, Ross D. ; Rice, William G. ; Poortinga, Gretchen ; Cullinane, Carleen ; Devlin, Jennifer R.

AbstractAbnormalities of the nucleolus, the site of transcription of the ribosomal genes (rDNA) by RNA Polymerase I (Pol I), have been recognized as diagnostic for cancer for more then a century. However, a critical, unresolved question has been whether the accelerated ribosome biogenesis responsible for the nucleolar changes is required for malignancy.Here we show that the PI3K/AKT pathway, deregulated in a high proportion of human tumours, is a critical regulator of ribosome biogenesis. Active AKT is sufficient to drive rRNA synthesis and ribosome biogenesis. Furthermore, AKT cooperates with c-MYC to drive these processes identifying the AKT//MYC network as a master controller of cell growth. Consistent with this concept, AKT activity is required for maximal activation of rRNA synthesis and tumour formation in the Eμ-Myc mouse model of Burkitt's lymphoma (1). Our findings raise the possibility that cancers characterized by unrestrained cellular growth may be vulnerable to therapeutic strategies that target ribosome biogenesis.To directly test this hypothesis, we used a novel selective small molecule inhibitor of Pol I transcription (CX-5461) (2), to show that Pol I can be targeted in vivo to treat tumors in mouse models of lymphoma and leukemia through the activation of p53-dependent apoptosis, while sparing normal hematologic cells. Thus, selective inhibition of Pol I transcription can serve as a novel therapeutic strategy for the treatment of cancer (3). A Phase 1 trial of this first-in-class molecule begins in 2013 at the Peter MacCallum Cancer Centre for patients with haematologic malignancies. Strikingly, allosteric inhibitors of AKT suppress rRNA synthesis independent of p53 and cooperate with CX-5461 in killing Eμ-Myc lymphomas providing a clear rationale for combining these agents in future trials.Citation Format: Megan J. Bywater, Katherine M. Hannan, Gretchen Poortinga, Jennifer R. Devlin, Carleen Cullinane, Denis Drygin, William G. Rice, Daniel Von Hoff, Ricky W. Johnstone, Grant A. McArthur, Ross D. Hannan, Richard B. Pearson. Inhibition of RNA Polymerase I as a strategy to treat cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4355. doi:10.1158/1538-7445.AM2013-4355

100 Deals associated with Cylene Pharmaceuticals, Inc.

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100 Translational Medicine associated with Cylene Pharmaceuticals, Inc.

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Pipeline

Pipeline Snapshot as of 23 Dec 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Phase 1 Clinical

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Pidnarulex ( G4 )	Hematologic Neoplasms More	Phase 1
CX-6258 ( PIM )	Neoplasms More	Discontinued
CX-3000-series (Cylene)	Neoplasms More	Discontinued
CX-1000-series (Cylene)	Neoplasms More	Discontinued
Itarnafloxin ( G4 )	Chronic lymphocytic leukaemia refractory More	Discontinued