Namodenoson Inhibits the Growth of Pancreatic Carcinoma via Deregulation of the Wnt/β-catenin, NF-κB, and RAS Signaling Pathways
Inbal Itzhak, Avital Bareket-Samish and Pnina Fishman

Biomolecules, 2023

Namodenoson Inhibits the Growth of Pancreatic Carcinoma via De-regulation of the Wnt/β-catenin Signaling Pathway
Fishman P, Bareket-Samish A and Itzhak I.

AACR special conference on pancreatic cancer, 2023

Effects of namodenoson on pancreatic carcinoma: Preclinical evidence.
Fishman P, Bareket-Samish A, Itzhak I.

ASCO meetings abstract number: e15134, 2023

Targeting the A3 adenosine receptor to treat hepatocellular carcinoma: anti-cancer and hepatoprotective effects.
Fishman P, Stemmer SM, Bareket-Samish A, Silverman MH, Kerns DW

Purinergic Signalling, 2023

Complete response induced by Namodenoson in advanced hepatocellular carcinoma: a case report
Pusca Ioana A, Lencioni R, Stemmer SM, Farbstein M, Harpaz Z, Silverman MH, and Fishman P.

Hepatology. 76, suppl, 2022

A3 adenosine receptor allosteric modulator CF602 reverses erectile dysfunction in a diabetic rat model
Itzhak I, Cohen S, Fishman S, Fishman P.

Andrologia. e14498. 2022.

Treatment of plaque psoriasis with piclidenoson: Efficacy and safety results from a phase 3 clinical trial (COMFORT).
Papp KA, Rizova S B, Gantcheva M, Simeonova ES, Brezoev P, Celic M,Groppa L, Blicharski T, Selmanagic A, Kalicka-Dudzik M, Calin C,Trailovic N, Ramon M, Bareket-Samish A, Harpaz Z, Farbstein M, Silverman M,Fishman P.

EADV Congress, abstract number: 3635.2022

Drugs Targeting the A3 Adenosine Receptor: Human Clinical Study Data
Fishman P

Molecules. 27(12): 3680. 2022

Inhibition of hepatocellular carcinoma growth and liver fibrosis by nanomolar cannabinoid concentrations
Itzhak I, Barer F, Fishman P.

Medical Cannabis and Cannabinoids; 5:36–60, 2022

Growth inhibition of hepatocellular carcinoma (HCC) by CBD rich T3/C15 cannabis fraction is mediated via the A3 adenosine receptor
Itzhak I, Barer F and Fishman P.

Hepatology 74 suppl 2021

The efficacy and safety of Piclidenoson vs Methotrexate in early rheumatoid arthritis: phase 3 randomized, double-blind, placebo-controlled study.
Reitblat T, Gurman- Balbir A, Harpaz Z, Farbstein M, Silverman M, Kerns W, Fishman P.

Arthritis Rheumatol. 73 ,suppl 10. 2021

Randomised clinical trial: A phase 2 double-blind study of namodenoson in non-alcoholic fatty liver disease and steatohepatitis
Safadi R, Braun R, Francis A, Milgrom Y, Massarwa M, Hakimian D, Hazou, Issachar A, Harpaz Z, Farbstein M, Fishman P.

Aliment Pharmacol Ther. 2021;00:1–11

Namodenoson in Advanced Hepatocellular Carcinoma and Child–Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial
Salomon M. Stemmer, Nebojsa S. Manojlovic, Mihai Vasile Marinca, Petar Petrov, Nelly Cherciu, Doina Ganea, Tudor Eliade Ciuleanu, Ioana Adriana Pusca, Muhammad Shaalan Beg, William T. Purcell, Adina-Emilia Croitoru, Rumyana Nedyalkova Ilieva, Sladjana Natoševi'c, Amedeia Lavinir Nita, Dimitar Nikolaev Kalev, Zivit Harpaz, Motti Farbstein, Michael H. Silverman, David Bristol, Inbal Itzhak and Pnina Fishman

Cancers 2021, 13, 187

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Dose-Finding Study Of The Efficacy And Safety Of Namodenoson (CF102), An A3 Adenosine Receptor (A3AR) Agonist, In Treating Non-Alcoholic Fatty Liver Disease (NAFLD) And Non-Alcoholic Steatohepatitis (NASH)
Safadi R , Braun M , Milgrom Y , Massarwa M, Hakimian D , Hazou W, Issachar A, Harpaz Z , Farbstein M , Itzhak I , Lev-Choain N, Silverman MH and Fishman P.

Hepatology: 72 suppl, 2020.

Namodenoson Anti-NAFLD/NASH Activity Is Mediated via De-Regulation of the Wnt/β-Catenin Pathway
Fishman P, Cohen S, Salhab A, Amer J, Itzhak I, Barer F, Safadi R.

Inflamm Intest Dis ;4:41–78.2019

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Efficacy and Safety of Namodenoson (CF102), an A3 Adenosine Receptor Agonist (A3AR), as a Second-line Treatment in Patients with Child-Pugh B (CPB) Advanced Hepatocellular Carcinoma (HCC)
Stemmer SM., Manojlovic NS, Marinca MV, Petrov P, Cherciu N, Ganea D, Ciuleanu TE, Puscas IA, Beg MS, Purcell WT, Croitoru AE, Ilieva RN, Natošević S, Nita AL, Kalev DN, Harpaz Z, Farbstein M, Silverman MH, Fishman P, Llovet JM.

JCO. 37: suppl. 2503. 2019

The A3 adenosine receptor agonist, namodenoson, ameliorates non?alcoholic steatohepatitis in mice
Pnina Fishman, Shira Cohen, Inbal Itzhak, Johnny Amer, Ahmad Salhab, Faina Barer, Rifaat Safadi.

International Journal of Molecular Medicine 44: 2256-2264

Targeting the A3 adenosine receptor to treat cytokine release syndrome in cancer immunotherapy
Cohen S, Fishman P.

Development and Therapy. 2019:13 491–497

Inhibition of IL-17 and IL-23 in Human Keratinocytes by the A3 Adenosine Receptor Agonist Piclidenoson
Cohen S, Barer F, Itzhak I, Silverman MH, Fishman P.

J Immunol Res. 2018 May 15;2018:2310970

CF602 Improves Erectile Dysfunction in Diabetic Rats
Cohen S, Fishman P.

j. juro.195, 4 suppl. 2016.

A3 adenosine receptor agonist, CF102, protects against hepatic ischemia/reperfusion injury following partial hepatectomy
Ohana G, Cohen S, Rath-Wolfson L, Fishman P.

Mol Med Rep. 2016 Nov;14(5):4335-4341

Treatment of Plaque-Type Psoriasis With Oral CF101: Data from a Phase II/III Multicenter, Randomized, Controlled Trial
Michael D, ..., Cosgarea MR, Morariu HS, Michael Z, Cristodor P, Nica C, Silverman MH, Bristol DR, Harpaz Z, Farbstein M, Cohen S, Fishman P.

J Drugs Dermatol. 15(8):931-8

The A3 adenosine receptor (A3AR): therapeutic target and predictive biological marker in rheumatoid arthritis.
Fishman P and Cohen S.

Clin Rheumatol, 2016; 35(9):2359-62

Adenosine Receptors – The Promise of A3AR Research
Pnina Fishman

Drug Development & Delivery March, 2015 Vol 15 No 1

Safety and efficacy of CF101 in rheumatoid arthritis patients: A phase II study. Arthritis Rheumatol
Stoilov RM, Licheva RN, Mihaylova MK, T Reitblat T, Dimitrov EA, Shimbova KM, Bhatia G, Pispati A, Balbir AG, Bagaria BR, Oparanov BA, Fishman S, Harpaz Z, Farbstein M, Cohen S, Silverman MH and Fishman P.

Arthritis Rheumatol.66: suppl 10. 2014

Therapeutic Effect of Oral CF101 in Patients with Rheumatoid Arthritis: A Randomized, Double-blind, Placebo-controlled Phase II Study
Rumen M Stoilov, Rodina N Licheva, Mariyana K Mihaylova, Tatiana Reitblat, Emil A Dimitrov, Krasimira M Shimbova, Girish Bhatia, Ameet Pispati, Alexandra Gurman- Balbir, BR Bagaria, Boytcho Aleksandrov Oparanov, Sari Fishman, Zivit Harpaz, Motti Farbstein, Shira Cohen, David Bristol, Michael H Silverman and Pnina Fishman

Immunome Res 2014, 11:1

A3 adenosine receptor allosteric modulator induces an anti-inflammatory effect: in vivo studies and molecular mechanism of action
Cohen S, Barer F, Bar-Yehuda S, IJzerman AP, Jacobson KA, Fishman P.

Mediators Inflamm. 2014;2014:708746. doi: 10.1155/2014/708746. Epub 2014

Targeting the A3 adenosine receptor for glaucoma treatment (Review)
Pnina Fishman, Shira Cohen, Sara Bar Yehuda.

Molecular Medicine Reports. DOI: 10.3892/mmr.2013.1413

CF102 for the Treatment of Hepatocellular Carcinoma: A Phase I/II, Open-Label, Dose-Escalation Study
Stemmer M, Benjaminov F, Medalia G, Ciuraru NB, Silverman MH, Bar-Yehuda S, Fishman S, Harpaz Z, Farbstein M, Cohen S, Patoka R, Singer B, Kerns WD, Fishman P.

The Oncologist. 18:25-26, 2013 Online version

Pharmacological and therapeutic effects of A3 adenosine receptor agonists
Pnina Fishman, Sara Bar-Yehuda, Bruce T. Liang and Kenneth A. Jacobson.

Drug Discov Today. 2012;17(7-8):359-66

Putative role of the adenosine A3 receptor in the antiproliferative action of N6-(2-isopentenyl)adenosine
Clara C. Blad, Jacobien K. von Frijtag Drabbe Künzel, Henk de Vries, Thea Mulder-Krieger, Sara Bar-Yehuda, Pnina Fishman, Adriaan P. IJzerman.

Purinergic Signal, 2011

Inhibition of experimental auto-immune uveitis by the A3 adenosine receptor agonist CF101
Sara Bar-Yehuda, Dror Luger, Avivit Ochaion, Shira Cohen, Renana Patokaa, Galina Zozulya, Phyllis B. Silver, Jose Maria Garcia Ruiz De Morales, Rachel R. Caspi, Pnina Fishman.

Int J Mol Med. Nov;28(5):727-3, 2011

CF101 for dry eye
Ashar JN, Mathur A, Sangwan V. Avni I, Sliverman MH, Bar Yehuda S, Fishman P.

Ophthalmology. 118:1011-1012, 2011

Treatment of plaque-type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial
David M, Akerman L, Ziv M, Kadurina M, Gospodinov D, Pavlotsky, Yankova R, Kouzeva V, Ramon M, Silverman MH, Fishman P.

Journal of the European Academy of Dermatology and Venereology, 2011

CF102 an A3 adenosine receptor agonist mediates anti-tumor and anti-inflammatory effects in the liver
Cohen S, Stemmer SM,Zozulya G, Ochaion A, Patoka R, Barer F, Bar-Yehuda S, Rath-Wolfson L, Jacobson KA, Fishman P.

Journal of Cellular Physiology, 226:2438-2447, 2011

Treatment of Dry Eye Syndrome with Orally Administered CF101. Data from a Phase 2 Clinical Trial
I. Avni, H. Garzozi, I. Barequet, F. Segev, D. Varssano, G. Sartani, N. Chetrit, E. Bakshi, D. Zadok, O. Tomkins, G. Litvin, K. Jacobson, S Fishman, Z. Harpaz, M. Farbstein, S. Bar Yehuda, M. Silverman, W. Kerns, D. Bristol, I Cohn, P. Fishman.

Ophthalmology , 117:1287-1293, 2010

Agonists and Antagonists: Molecular Mechanisms and Therapeutic Applications. In: P.A. Borea (ed.), A3 Adenosine Receptors from Cell Biology to Pharmacology and Therapeutics
Fishman, P., Bar-Yehuda, S., Varani, K., Gessi, S., Merighi, S., and Borea, PA.

Rheumatoid Arthritis: History, Molecular Mechanisms and Therapeutic Applications. P.A. Borea (ed.), A3 Adenosine Receptors from Cell Biology to Pharmacology and Therapeutics
Fishman, P., Bar-Yehuda, S.

Induction of an Antiinflammatory Effect and Prevention of Cartilage Damage in Rat Knee Osteoarthritis by CF101 Treatment
S. Bar-Yehuda, L. Rath-Wolfson, L. Del Valle, A. Ochaion, S. Cohen, R. Patoka, G. Zozulya, F. Barer, E. Atar, S. Pin˜a-Oviedo, G. Perez-Liz, D. Castel, and P. Fishman

ARTHRITIS & RHEUMATISM Vol. 60, No. 10, (2009) 3061–3071

Adenosine Receptors and Cancer
P. Fishman, S. Bar-Yehuda, M. Synowitz, J.D. Powell, K.N. Klotz, S. Gessi, and P.A. Borea.

Handbook of Experimental Pharmacology 193 (2009) 399-441

The anti-inflammatory target A3 adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease
A. Ochaion, S. Bar-Yehuda, S. Cohen, F. Barer, R. Patoka, H. Amital, T. Reitblat, A. Reitblat, J. Ophir, I. Konfino, Y. Chowers, S. Ben-Horin, P. Fishman

Cellular Immunology 258 (2009) 115–122

The A3 adenosine receptor agonist CF502 inhibits the PI3K, PKB/Akt and NF-kappaB signaling pathway in synoviocytes from rheumatoid arthritis patients and in adjuvant-induced arthritis rats
Ochaion A, Bar-Yehuda S, Cohen S, Amital H, Jacobson KA, Joshi BV, Gao ZG, Barer F, Patoka R, Del Valle L, Perez-Liz G, Fishman P.

Biochem Pharmacol. 2008 ;76(4):482-94

The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-kB signal transduction pathways
Bar-Yehuda S., Stemmer S.M., Madi L., Castel D., Ochaion A., Cohen S., Barer F., Zabutti A., Perez-Liz G., Del Valle L., Fishman P.

Int J Onc 33: 287-295, 2008

Clinical Evidence for Utilization of the A3 Adenosine Receptor as a Target to Treat Rheumatoid Arthritis: Data from a Phase II Clinical Trial
Fishman-Furman S., Farbstein M., Bar-Yehuda S., Fishman P.

The Journal of Rheumatology 2008;35(1):41-8

The Anti-inflammatory Effect of A3 Adenosine Receptor Agonists: A Novel Targeted Therapy for Rheumatoid Arthritis
Bar Yehuda S., Silvermen M., Kerns W., Ochaion, A., Cohen, S., Fishman, P.

Expert Opin. Investig. Drugs (2007) 16(10):1601-1613

The Anti-Cancer Effect of A3 Adenosine Receptor Agonists: A Novel Targeted Therapy
Fishman P., Jacobson KA., Ochaion A., Cohen S., Bar Yehuda S.

Immun, Endoc. & Metab. Agents in Med Chem. 7:298-303, 2007

Over-expression of A3 Adenosine Receptor in PBMNC of Rheumatoid Arthritis Patients: Involvement of NF-kB in mediating Receptor Level
Madi L., Cohn, S. Ochaion A., Bar-Yehuda S., Barer F., Fishman P.

J. Rheumatology. 34:20-26, 2007

Adenosine, Tumors, and Immunity. ADENOSINE RECEPTORS: Therapeutic Aspects for Inflammatory and Immune Diseases
Fishman P., Bar-Yehud, S., Madi L.

Taylor&Francis; London. P: 299-312, 2007

Methotrexate enhances the anti-inflammatory effect of CF101 via upregulation of the A3 adenosine receptor expression
Ochaion A, Bar-Yehuda S, Cohn S, Del Valle L, Perez-Liz G, Madi L, Barer F, Farbstein M, Fishman-Furman S, Reitblat T, Reitblat A, Amital H, Levi Y, Molad Y, Mader R, Tishler M, Langevitz P, Zabutti A, Pnina Fishman.

Arthritis Research & Therapy 2006, 8:R169

IB-MECA, an A3 adenosine receptor agonist prevents bone resorption in rats with adjuvant induced arthritis
Rath-Wolfson L., Bar-Yehuda S. Madi L., Fishman P.

Clin Exp Rheumatol. 2006; 24(4):400-6

The PI3K-NF-kB signal transduction pathway is involved in mediating the anti-inflammatory effect of IB-MECA in adjuvant induced arthritis
Fishman P., Bar-Yehuda S., Madi L., Rath-Wolfson L., Ochaion A., Cohen S. and Baharav E.

Arthritis Research & Therapy 2006, 8:R33

CF101, an Agonist to the A3 Adenosine Receptor Enhances the Chemotherapeutic Effect of 5-Flurouracil in a Colon Carcinoma Murine Model
Bar-Yehuda, S., Madi,L., Silberman, D., Slosman G., Shkapenuk, M., Fishman, P.

Neoplasia. 7:85-90. 2005

The Anti-inflammatory Effect of A3 Adenosine Receptor Agonists in Murine Autoimmune Arthritis Models
Baharav, E., Bar-Yehuda, S., Madi, L., Silberman, D., Rath-Wolfson, L., Halpren, M., Ochaion, A., Weinberger, A., Fishman, P.

J Rheumatol. 32:469-76. 2005

Tolerability, pharmacokinetics, and concentration-dependent hemodynamic effects of oral CF101, an A3 adenosine receptor agonist, in healthy young men
van Troostenburg, A. R., Clark, E. V., Carey, W. D. H., Warrington, S. J., Kerns, W.D., Cohn, I., Silverman, M. H., Bar-Yehuda, S., Fong, K.L. L., Fishman, P.

Int J Clin Pharmacol Ther. 42: 534-42, 2004

The A3 Adenosine Receptor is Highly Expressed in Tumor vs. Normal Cells: Potential Target for Tumor Growth Inhibition
Madi, L., Ochaion, A., Rath-Wolfson, L., Bar-Yehuda, S., Erlanger, A., Ohana, G., Harish, A., Merimski, O., Barer, F., Fishman, P.

Clinical Cancer Research, 10: 4472-4479, 2004

An agonist to the A3 adenosine receptor inhibits colon carcinoma growth in mice via modulation of GSK-3ß and NF-kB
Fishman, P., Bar-Yehuda, S., Ohana, G., Ochaion, A., Engelberg, A., Barer, F., Madi, L.

Oncogene, 23: 2465-2471, 2004

A3 Adenosine Receptor Agonist Potentiates Natural Killer Cell Activity
Harish A., Ohana G., Fishman P., Arnon O., Bar-Yehuda S.

International J Oncol, 23:1245-1249. 2003

Inhibition of primary colon carcinoma growth and liver metastasis by the A3 adenosine receptor agonist
Ohana, G., Bar-Yehuda, S., Arich, A., Madi L., Dreznick Z., Silberman D., Slosman G., Volfsson-Rath, L., Pnina Fishman.

CF101. British J Cancer, 89: 155

A3 adenosine receptor activation in melanoma cells: association between receptor fate and tumor growth inhibition
Madi, L., Bar-Yehuda, S., Barer, F., Ardon, E., Ochaion, A., Fishman, P.

JBC. 278:42121-42130, 2003

Targeting the A3 adenosine receptor for cancer therapy: inhibition of Prostate carcinoma cell growth by A3AR agonist
Fishman, P., Bar-Yehuda, S., Rath-Wolfson, L., Ardon, E., Barrer, F., Ochaion, A., Madi, L.

Anticancer Res. 23:2077-2083, 2003

Modulation of the A3 adenosine receptor by low agonist concentration induced anti-tumor and myelostimulation effects
Merimsky O, Madi L, Bar-Yehuda S, Fishman P.

Drug Dev Res. 58:386-389, 2003

Pharmacology and therapeutic applications of A3 receptor subtype
Fishman, P., Bar-Yehuda, S.

Curr Top Med Chem. 3:463-469, 2003

Suppression of experimental zymosan induced arthritis by intraperitoneal administration of adenosine
Baharav, E., Dubrosin, A., Fishman, P., Bar-Yehuda, S., Halpern, M., Weinberger, A.

Drug Dev Res. 57 :182-186, 2002

Agonists to the A3 adenosine receptor induce G-CSF production via NF-kappaB activation: a new class of myeloprotective agents
Bar-Yehuda, S., Madi, L., Barak, D., Mittelman, M., Ardon, E., Ochaion, A, Cohn, S., Fishman, P.

Exp Hematol. 30:1390-1398, 2002

Fishman, P., Bar-Yehuda, S., Madi, L., Cohn, I. A3 adenosine receptor as a target for cancer therapy.

Anti-cancer Drugs. 13:437-443, 2002

Evidence for involvement of Wnt signaling pathway in IB-MECA mediated suppression of melanoma cells
Fishman, P., Madi, L., Bar-Yehuda, S., Barer, F., Del Valle, L., Khalili, K.

Oncogene 21:4060-4064, 2002

The A3 adenosine receptor as a new target for cancer therapy and chemoprotection
Fishman, P., Bar-Yehuda, S., Barer, F., Madi, L., Multani, A.F, Pathak, S.

Exp Cell Res. 269: 230-236, 2001

Ohana, G., Bar-Yehuda, S, Barer, F., Fishman, P. Differential effect of adenosine on tumor and normal cell growth: focus on the A3 adenosine receptor.

J Cell Physiol. 186: 19-23. 2001

Adenosine acts as a chemoprotective agent by stimulating G-CSF production: a role for A1 and A3 adenosine receptors
Fishman, P., Bar-Yehuda, S., Farbstein, T., Barer, F., Ohana, G.

J Cell Physiol. 183: 393-398, 2000

Adenosine acts as an inhibitor of lymphoma cell growth: a major role for the A3 adenosine receptor
Fishman, P., Bar-Yehuda, S., Ohana, G., Pathak, S., Wasserman, L., Barer, F., Multani, A.F.

Eur. J Cancer 36:1452-1458, 2000

Resistance of muscles to tumor metastasis: a role for A3 adenosine receptor agonists
Bar-Yehuda, S., Barer, F., Volfsson, L., Fishman, P.

Neoplasia 3: 125-131, 2001

Oral administration of muscle derived small molecules inhibits tumor spread while promoting normal cell growth in mice
Bar-Yehuda, S., Farbstein, T., Barer, F., Ohana, G., Fishman, P.

Clin. Exp. Metastasis 17:513-535, 1999

Adenosine and other low molecular weight factors released by muscle cells inhibit tumor cell growth
Fishman, P., Bar-Yehuda, S., Vagman, L.

Cancer Res. 58:3181-3187, 1998

Mononuclear cells release low molecular weight factors with anti-cancer activity: A lower level of production by cells of cancer patients
Cohen-Aloro, D., Merimsky, O., Bar-Yehuda, S., Klein, B., Kayzer, S., Fishman, P.

Int. J Oncol. 12:921-925, 1998.

Muscle cells produce a low molecular weight factor with anti-cancer activity
Djaldetti M., Sredni B., Zigelman R., Verber M., Fishamn P.

Clin Exp Metastasis 14:189-196, 1996.

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