New Data Confirms Anti-tumor Efficacy of Annamycin in Both Human and Murine AML Models

On October 29, 2019, Moleculin announced the presentation of a poster at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference today in Boston, MA. The poster, entitled “Dose and Schedule-Dependent Efficacy of Liposomal Annamycin in Pre-clinical Models of Acute Myeloid Leukemia,” presents data documenting the high activity of Annamycin against AML, including in vitro studies in a panel of human AML cell lines, as well as in vivo studies in both human and murine AML models developed under the Company’s sponsored research agreement with MD Anderson Cancer Center.

Preclinical Pancreatic Cancer Data Presented at American Association for Cancer Research Annual Meeting

On April 3, 2019, Moleculin announced that preclinical data supporting activity of its STAT3-inhibiting Immune/Transcription Modulators was presented by Dr. Waldemar Priebe, Founder and Chair of the Scientific Advisory Board of Moleculin at the 2019 AACR in Atlanta, GA. The presentation included data resulting from preclinical evaluation in pancreatic cancer models of STAT3 inhibitors WP1066 and WP1732, both discovered at MD Anderson Cancer Center and licensed by Moleculin. WP1066 is an orally bioavailable drug with significant brain uptake that is currently in Phase I clinical studies in patients with brain tumors.

Annamycin Bibliography

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WP1066 Bibliography

Akerman, A. W., R. E. Stroud, R. W. Barrs, R. T. Grespin, L. T. McDonald, R. A. C. LaRue, R. Mukherjee, J. S. Ikonomidis, J. A. Jones and J. M. J. A. o. v. s. Ruddy (2018). “Elevated Wall Tension Initiates Interleukin-6 Expression and Abdominal Aortic Dilation.”  46: 193-204.

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Cheng, C.-C., L.-H. Shi, X.-J. Wang, S.-X. Wang, X.-Q. Wan, S.-R. Liu, Y.-F. Wang, Z. Lu, L.-H. Wang and Y. J. I. j. o. o. Ding (2018). “Stat3/Oct-4/c-Myc signal circuit for regulating stemness-mediated doxorubicin resistance of triple-negative breast cancer cells and inhibitory effects of WP1066.”  53(1): 339-348.

Gilbert, A. N., J. C. Anderson, C. W. Duarte, R. S. Shevin, C. P. Langford, R. Singh, G. Y. Gillespie and C. D. J. S. r. Willey (2018). “Combinatorial Drug Testing in 3D Microtumors Derived from GBM Patient-Derived Xenografts Reveals Cytotoxic Synergy in Pharmacokinomics-informed Pathway Interactions.”

Hu, X., J. Ma, V. Vikash, J. Li, D. Wu, Y. Liu, J. Zhang, W. J. D. d. Dong and sciences (2018). “Thymoquinone Augments Cisplatin-Induced Apoptosis on Esophageal Carcinoma Through Mitigating the Activation of JAK2/STAT3 Pathway.”  63(1): 126-134.

Li, H., J. Min, X. Mao, X. Wang, Y. Yang and Y. J. A. j. o. t. r. Chen (2018). “Edaravone ameliorates experimental autoimmune thyroiditis in rats through HO-1-dependent STAT3/PI3K/Akt pathway.”  10(7): 2037.

Li, Y., J. Li, Q. Wei, Z. Zhang, J. Wu and A. J. S. d. x. x. b. Y. x. b. J. o. S. U. M. s. e. Wang (2018). “Study of Kinase Inhibitor WP1066 on the STAT3/JAK2 of Prostate Stromal Cells.”  48(1): 65-68.

Lin, W.-H., M. He, Y. N. Fan and R. A. J. J. o. n. Baines (2018). “An RNAi-mediated screen identifies novel targets for next-generation antiepileptic drugs based on increased expression of the homeostatic regulator pumilio.”  32(2): 106-117.

Lu, Q.-B., H.-P. Wang, Z.-H. Tang, H. Cheng, Q. Du, Y.-B. Wang, W.-B. Feng, K.-X. Li, W.-W. Cai and L.-Y. J. B. e. B. A.-M. B. o. D. Qiu (2018). “Nesfatin-1 functions as a switch for phenotype transformation and proliferation of VSMCs in hypertensive vascular remodeling.”  1864(6): 2154-2168.

Ma, B., L. Yang, R. Jing, J. Liu, Y. Quan, Q. Hui, J. Li, L. Qin and C. J. E. e. r. Pei (2018). “Effects of Interleukin-6 on posterior capsular opacification.”  172: 94-103.

Masliantsev, K., B. Pinel, A. Balbous, P.-O. Guichet, G. Tachon, S. Milin, J. Godet, M. Duchesne, A. Berger and C. J. O. Petropoulos (2018). “Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome.”  9(3): 3968.

Sun, S., Y. Wu, W. Guo, F. Yu, L. Kong, Y. Ren, Y. Wang, X. Yao, C. Jing and C. J. C. C. R. Zhang (2018). “STAT3/HOTAIR signaling axis regulates HNSCC growth in an EZH2-dependent manner.

Xu, J., H. Yao, H. Wang, C. Li and J.-Y. J. F. i. i. Fang (2018). “Cancer cell-intrinsic PD-1 and implications in combinatorial immunotherapy.”  9: 1774.

Yang, X., L. Shi, C. Yi, Y. Yang, L. Chang and D. J. I. J. o. U. Song (2018). “Astrocyte elevated gene‐1 promotes invasion and epithelial–mesenchymal transition in bladder cancer cells through activation of signal transducer and activator of transcription 3.”  25(2): 157-163.

Yi, M., W. Wang, S. Chen, Y. Peng, J. Li, J. Cai, Y. Zhou, Q. Peng, Y. Ban and Z. J. M. b. r. Zeng (2018). “Dual-functionality of RASSF1A overexpression in A375 cells is mediated by activation of IL-6/STAT3 regulatory loop.”  45(5): 1277-1287.

Bhunia, S., V. Vangala, D. Bhattacharya, H. G. Ravuri, M. Kuncha, S. Chakravarty, R. Sistla and A. J. M. p. Chaudhuri (2017). “Large Amino Acid Transporter 1 Selective Liposomes of l-DOPA Functionalized Amphiphile for Combating Glioblastoma.”  14(11): 3834-3847.

Chen, L., L. Zhao, A. Samanta, S. M. Mahmoudi, T. Buehler, A. Cantilena, R. J. Vincent, M. Girgis, J. Breeden and S. J. P. o. Asante (2017). “STAT3 balances myocyte hypertrophy vis-à-vis autophagy in response to Angiotensin II by modulating the AMPKα/mTOR axis.”  12(7): e0179835.

Cherepkova, M. Y., G. S. Sineva, V. A. J. C. d. Pospelov and disease (2017). “Leukemia inhibitory factor (LIF) withdrawal activates mTOR signaling pathway in mouse embryonic stem cells through the MEK/ERK/TSC2 pathway.”  7(1): e2050.

D’aiuto, L., K. Williamson, P. Dimitrion, J. McNulty, C. E. Brown, C. B. Dokuburra, A. J. Nielsen, W. J. Lin, P. Piazza and M. E. J. A. r. Schurdak (2017). “Comparison of three cell-based drug screening platforms for HSV-1 infection.”  142: 136-140.

Honda, S., D. Sadatomi, Y. Yamamura, K. Nakashioya, S. Tanimura and K. J. C. s. Takeda (2017). “WP1066 suppresses macrophage cell death induced by inflammasome agonists independently of its inhibitory effect on STAT3.”  108(3): 520-527.

Hosokawa, Y., I. Hosokawa, K. Ozaki, T. J. C. P. Matsuo and Biochemistry (2017). “IL-27 modulates chemokine production in TNF-α-stimulated human oral epithelial cells.”  43(3): 1198-1206.

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Jane, E. P., D. R. Premkumar, P. A. Sutera, J. M. Cavaleri and I. F. J. M. c. Pollack (2017). “Survivin inhibitor YM155 induces mitochondrial dysfunction, autophagy, DNA damage and apoptosis in Bcl‐xL silenced glioma cell lines.”  56(4): 1251-1265.

Kim, B., H. S. Kim, S. Kim, G. Haegeman, B. K. Tsang, D. N. Dhanasekaran, Y. S. J. C. r. Song and t. o. j. o. K. C. Association (2017). “Adipose stromal cells from visceral and subcutaneous fat facilitate migration of ovarian cancer cells via IL-6/JAK2/STAT3 pathway.”  49(2): 338.

Kong, G., Y. Jiang, X. Sun, Z. Cao, G. Zhang, Z. Zhao, Y. Zhao, Q. Yu and G. J. O. r. Cheng (2017). “Irisin reverses the IL-6 induced epithelial-mesenchymal transition in osteosarcoma cell migration and invasion through the STAT3/Snail signaling pathway.”  38(5): 2647-2656.

Lim, R., L. Li, N. Chew and E. J. B. Yong (2017). “The prenylflavonoid Icaritin enhances osteoblast proliferation and function by signal transducer and activator of transcription factor 3 (STAT-3) regulation of CXC chemokine receptor type 4 (CXCR4) expression.”  105: 122-133.

Ma, C., H. Horlad, C. Pan, H. Yano, K. Ohnishi, Y. Fujiwara, M. Matsuoka, A. Lee, T. Niidome, R. J. J. o. c. Yamanaka and e. hematopathology (2017). “Stat3 inhibitor abrogates the expression of PD-1 ligands on lymphoma cell lines.”  57(1): 21-25.

Sau, S., S. K. Mondal, S. K. Kashaw, A. K. Iyer, R. J. M. Banerjee and c. biochemistry (2017). “Combination of cationic dexamethasone derivative and STAT3 inhibitor (WP1066) for aggressive melanoma: a strategy for repurposing a phase I clinical trial drug.”  436(1-2): 119-136.

Song, L., L. Guo, Z. J. T. Li and a. pharmacology (2017). “Molecular mechanisms of 3, 3′ 4, 4′, 5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells.”  322: 75-88.

Tashiro, T., H. Okuyama, H. Endo, K. Kawada, Y. Ashida, M. Ohue, Y. Sakai and M. J. P. o. Inoue (2017). “In vivo and ex vivo cetuximab sensitivity assay using three-dimensional primary culture system to stratify KRAS mutant colorectal cancer.”  12(3): e0174151.

Tian, D.-S., J. Peng, M. Murugan, L. Feng, J.-L. Liu, U. B. Eyo, L.-J. Zhou, R. Mogilevsky, W. Wang and L.-J. J. J. o. N. Wu (2017). “Chemokine CCL2-CCR2 signaling induces neuronal cell death via STAT3 activation and IL-1β production after status epilepticus.” 0315-0317.

Tsujita, Y., A. Horiguchi, S. Tasaki, M. Isono, T. Asano, K. Ito, T. Asano, Y. Mayumi and T. J. O. r. Kushibiki (2017). “STAT3 inhibition by WP1066 suppresses the growth and invasiveness of bladder cancer cells.”  38(4): 2197-2204.

Tsurumaki, H., H. Katano, K. Sato, R. Imai, S. Niino, Y. Hirabayashi, S. J. B. Ichikawa and b. r. communications (2017). “WP1066, a small molecule inhibitor of the JAK/STAT3 pathway, inhibits ceramide glucosyltransferase activity.”  491(2): 265-270.

Xiao, J., Y. Gong, Y. Chen, D. Yu, X. Wang, X. Zhang, Y. Dou, D. Liu, G. Cheng and S. J. A. J. o. P.-R. P. Lu (2017). “IL-6 promotes epithelial-to-mesenchymal transition of human peritoneal mesothelial cells possibly through the JAK2/STAT3 signaling pathway.”  313(2): F310-F318.

Yao, W., H. Li, G. Luo, X. Li, C. Chen, D. Yuan, X. Chi, Z. Xia, Z. J. F. R. B. Hei and Medicine (2017). “SERPINB1 ameliorates acute lung injury in liver transplantation through ERK1/2-mediated STAT3-dependent HO-1 induction.”  108: 542-553.

Zhang, L., Y. Wang, J. Ma, X. Lai, J. Fang, G. Li, L. Xu, G. Pan and Z. J. A. j. o. t. r. Chen (2017). “Exogenous MSCs ameliorate hypoxia/reoxygenation injury in renal tubular epithelial cells through JAK/STAT signaling pathway-mediated regulation of HMGB1.”  9(5): 2412.

Zhang, W., X. Wu, L. Hu, Y. Ma, Z. Xiu, B. Huang, Y. Feng, X. J. O. R. F. P. Tang and C. C. Therapeutics (2017). “Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial‐Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer Cells.”  25(5): 843-852.

Geng, L., X. Li, X. Zhou, X. Fang, D. Yuan and X. J. O. r. Wang (2016). “WP1066 exhibits antitumor efficacy in nasal‑type natural killer/T-cell lymphoma cells through downregulation of the STAT3 signaling pathway.”  36(5): 2868-2874.

Hong, L., J. Ma, H. Zhu, H. Cai, J. Dong, M. Li, Q. Huang and A. J. T. C. R. Wang (2016). “STAT3 signaling pathway regulates glioma stem cells induced host macrophage malignance.”  5(6): 805-816.

Hristova, M., E. Rocha‐Ferreira, X. Fontana, L. Thei, R. Buckle, M. Christou, S. Hompoonsup, N. Gostelow, G. Raivich and D. J. J. o. n. Peebles (2016). “Inhibition of Signal Transducer and Activator of Transcription 3 (STAT 3) reduces neonatal hypoxic‐ischaemic brain damage.”  136(5): 981-994.

Jiang, J., Y. Liu, Y. Tang, L. Li, R. Zeng, S. Zeng, M. J. O. Zhong and therapy (2016). “ALDH1A1 induces resistance to CHOP in diffuse large B-cell lymphoma through activation of the JAK2/STAT3 pathway.”  9: 5349.

Jin, X.-T., M.-L. Chen, R.-J. Li, Q. An, L. Song, Y. Zhao, H. Xiao, L. Cheng and Z.-Y. J. A. o. t. Li (2016). “Progression and inflammation of human myeloid leukemia induced by ambient PM2. 5 exposure.”  90(8): 1929-1938.

Kim, S., J.-W. Hong, K. W. J. M. Park and c. biochemistry (2016). “B cell translocation gene 2 (Btg2) is regulated by Stat3 signaling and inhibits adipocyte differentiation.”  413(1-2): 145-153.

Kong, L., A. Liu, X. Zhou, Y. Ren, Y. Huang, S. Liu and L. J. T. M. J. Zhang (2016). “The STAT-3 inhibitor WP1066 promotes oral squamous cell carcinoma invasiveness by cisplatin in vitro.”  44(1): 38-42.

Lii, C.-K., J.-W. Chang, J.-J. Chen, H.-W. Chen, K.-L. Liu, S.-L. Yeh, T.-S. Wang, S.-H. Liu, C.-H. Tsai and C.-C. J. O. Li (2016). “Docosahexaenoic acid inhibits 12-O-tetradecanoylphorbol-13-acetate-induced fascin-1-dependent breast cancer cell migration by suppressing the PKCδ-and Wnt-1/β-catenin-mediated pathways.”  7(18): 25162.

Si, Y., Y. Zhang, L. Han, L. Chen, Y. Xu, F. Sun, M. Ji, J. Yang and H. J. P. o. Bao (2016). “Dexmedetomidine acts via the JAK2/STAT3 pathway to attenuate isoflurane-induced neurocognitive deficits in senile mice.”  11(10): e0164763.

Song, H., J. Xu, N. Lv, Y. Zhang, F. Wu, H. Li, L. Shao, Q. Mu, F. Wang, D. J. B. Tang and b. r. communications (2016). “Irisin reverses platelet derived growth factor-BB-induced vascular smooth muscle cells phenotype modulation through STAT3 signaling pathway.”  479(2): 139-145.

Wang, D., Y. Saga, N. Sato, T. Nakamura, O. Takikawa, H. MIzUKAMI, S. MATSUbARA and H. J. I. j. o. o. Fujiwara (2016). “The hepatocyte growth factor antagonist NK4 inhibits indoleamine-2, 3-dioxygenase expression via the c-Met-phosphatidylinositol 3-kinase-AKT signaling pathway.”  48(6): 2303-2309.

Wang, H., B. Xie, Y. Kong, Y. Tao, G. Yang, M. Gao, H. Xu, F. Zhan, J. Shi and Y. J. O. Zhang (2016). “Overexpression of RPS27a contributes to enhanced chemoresistance of CML cells to imatinib by the transactivated STAT3.”  7(14): 18638.

Xue, J., A. Zhou, Y. Wu, S.-A. Morris, K. Lin, S. Amin, R. Verhaak, G. Fuller, K. Xie and A. B. J. C. r. Heimberger (2016). “miR-182-5p induced by STAT3 activation promotes glioma tumorigenesis.”  76(14): 4293-4304.

Yu, J., X. Yuan, Y. Liu, K. Zhang, J. Wang, H. Zhang and F. J. L. Liu (2016). “Delayed administration of WP1066, an STAT3 inhibitor, ameliorates radiation-induced lung injury in mice.”  194(1): 67-74.

Adoro, S., J. R. Cubillos-Ruiz, X. Chen, M. Deruaz, V. D. Vrbanac, M. Song, S. Park, T. T. Murooka, T. E. Dudek and A. D. Luster (2015). “IL-21 induces antiviral microRNA-29 in CD4 T cells to limit HIV-1 infection.” Nature Communications 6:7562.

Barbosa, B. F., J. B. Lopes-Maria, A. O. Gomes, M. B. Angeloni, A. S. Castro, P. S. Franco, M. L. Fermino, M. C. Roque-Barreira, F. Ietta and O. A. Martins-Filho (2015). “IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells.” Biology of Reproduction 92(3):82, 1-13.

Garner, J. M., D. W. Ellison, D. Finkelstein, D. Ganguly, Z. Du, M. Sims, C. H. Yang, R. B. Interiano, A. M. Davidoff and L. M. Pfeffer (2015). “Molecular Heterogeneity in a Patient-Derived Glioblastoma Xenoline Is Regulated by Different Cancer Stem Cell Populations.” PloS ONE 10(12): e0125838

Jin, X.-T., M.-L. Chen, R.-J. Li, Q. An, L. Song, Y. Zhao, H. Xiao, L. Cheng and Z.-Y. Li (2015). “Progression and inflammation of human myeloid leukemia induced by ambient PM2. 5 exposure.” Archives of Toxicology: pp1-10.

King, C. A., X. Li, A. Barbachano-Guerrero and S. Bhaduri-McIntosh (2015). “STAT3 Regulates Lytic Activation of Kaposi’s Sarcoma-Associated Herpesvirus.” Journal of Virology 89(22): 11347-11355.

Kiprianova, I., J. Remy, N. Milosch, I. V. Mohrenz, V. Seifert, A. Aigner and D. Kögel (2015). “Sorafenib sensitizes glioma cells to the BH3 mimetic ABT-737 by targeting MCL1 in a STAT3-dependent manner.” Neoplasia 17(7): 564-573.

Lee, H.-T., J. Xue, P.-C. Chou, A. Zhou, P. Yang, C. A. Conrad, K. D. Aldape, W. Priebe, C. Patterson and R. Sawaya (2015). “Stat3 orchestrates interaction between endothelial and tumor cells and inhibition of Stat3 suppresses brain metastasis of breast cancer cells.” Oncotarget 6(12): 10016-10029.

Lu, K., N. Chen, X.-x. Zhou, X.-l. Ge, L.-l. Feng, P.-p. Li, X.-y. Li, L.-y. Geng and X. Wang (2015). “The STAT3 inhibitor WP1066 synergizes with vorinostat to induce apoptosis of mantle cell lymphoma cells.” Biochemical and Biophysical Research Communications 464(1): 292-298.

Lu, K., X.-s. Fang, L.-l. Feng, Y.-j. Jiang, X.-x. Zhou, X. Liu, P.-p. Li, N. Chen, M. Ding and N. Wang (2015). “The STAT3 inhibitor WP1066 reverses the resistance of chronic lymphocytic leukemia cells to histone deacetylase inhibitors induced by interleukin-6.” Cancer Letters 359(2): 250-258.

Malinska, M., I. Fokt, W. Priebe and K. Wozniak (2015). “Bromine Atom Interactions in Biologically Active Acrylamide Derivatives.” Crystal Growth & Design 15(6): 2632-2642.

Okamoto, M., K. Nasu, W. Abe, Y. Aoyagi, Y. Kawano, K. Kai, M. Moriyama and H. Narahara (2015). “Enhanced miR-210 expression promotes the pathogenesis of endometriosis through activation of signal transducer and activator of transcription 3.” Human Reproduction 30(3): 632-641.

Phi, J. H., S.-A. Choi, S.-K. Kim, K.-C. Wang, J. Y. Lee and D. G. Kim (2015). “Overcoming Chemoresistance of Pediatric Ependymoma by Inhibition of STAT3 Signaling.” Translational Oncology 8(5): 376-386.

Qureshi, R., O. Yildirim, A. Gasser, C. Basmadjian, Q. Zhao, J.-P. Wilmet, L. Désaubry and C. G. Nebigil (2015). “FL3, a Synthetic Flavagline and Ligand of Prohibitins, Protects Cardiomyocytes via STAT3 from Doxorubicin Toxicity.” PloS ONE 10(11): e0141826.

Raible, D. J., L. C. Frey, Y. C. Del Angel, J. Carlsen, D. Hund, S. J. Russek, B. Smith and A. R. Brooks-Kayal (2015). “JAK/STAT pathway regulation of GABA A receptor expression after differing severities of experimental TBI.” Experimental Neurology 271: 445-456.

Rath, B. H., A. Wahba, K. Camphausen and P. J. Tofilon (2015). “Coculture with astrocytes reduces the radiosensitivity of glioblastoma stem‐like cells and identifies additional targets for radiosensitization.” Cancer Medicine 4(11): 1705-1716.

Shen, Y., L. Meng, H. Sun, Y. Zhu and H. Liu (2015). “Cochinchina Momordica Seed Suppresses Proliferation and Metastasis in Human Lung Cancer Cells by Regulating Multiple Molecular Targets.” The American Journal of Chinese Medicine 43(01): 149-166.

Sun, S.-S., X. Zhou, Y.-Y. Huang, L.-P. Kong, M. Mei, W.-Y. Guo, M.-H. Zhao, Y. Ren, Q. Shen and L. Zhang (2015). “Targeting STAT3/miR-21 axis inhibits epithelial-mesenchymal transition via regulating CDK5 in head and neck squamous cell carcinoma.” Molecular Cancer 14(1): 1.

Yu, J., X. Yuan, Y. Liu, K. Zhang, J. Wang, H. Zhang and F. Liu (2015). “Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice.” Lung, Epub ahead of print, doi:10.1007/s000408-015-9821-8.

Yuan, X., J. Du, S. Hua, H. Zhang, C. Gu, J. Wang, L. Yang, J. Huang, J. Yu and F. Liu (2015). “Suppression of autophagy augments the radiosensitizing effects of STAT3 inhibition on human glioma cells.” Experimental Cell Research 330(2): 267-276.

Hristova, M., E. Rocha‐Ferreira, X. Fontana, L. Thei, R. Buckle, M. Christou, S. Hompoonsup, N. Gostelow, G. Raivich and D. Peebles (2015). “Inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) reduces neonatal hypoxic‐ischemic brain damage.” Journal of Neurochemistry. doi: 10.1111/jnc.13490

Assi, H. H., C. Paran, N. VanderVeen, J. Savakus, R. Doherty, E. Petruzzella, J. D. Hoeschele, H. Appelman, L. Raptis and T. Mikkelsen (2014). “Preclinical characterization of signal transducer and activator of transcription 3 small molecule inhibitors for primary and metastatic brain cancer therapy.” Journal of Pharmacology and Experimental Therapeutics 349(3): 458-469.

Cao, Y., X. Zhou, M. Zhou, D. Xu, Q. Ma, P. Zhang, X. Huang, Q. Li, D. Ma and J. Zhou (2014). “Inhibition of STAT3 activity re-activates anti-tumor immunity but fails to restore the immunogenicity of tumor cells in a B-cell lymphoma model.” Cancer Biology & Therapy 15(9): 1153-1162.

Cho, K. H., M. J. Choi, K. J. Jeong, J. J. Kim, M. H. Hwang, S. C. Shin, C. G. Park and H. Y. Lee (2014). “A ROS/STAT3/HIF‐1α signaling cascade mediates EGF‐induced TWIST1 expression and prostate cancer cell invasion.” The Prostate 74(5): 528-536.

Gao, W., J. McCormick, M. Connolly, E. Balogh, D. J. Veale and U. Fearon (2014). “Hypoxia and STAT3 signalling interactions regulate pro-inflammatory pathways in rheumatoid arthritis.” Annals of the Rheumatic Diseases: 74(6), 1275-83.

Grabenstatter, H., Y. C. Del Angel, J. Carlsen, M. Wempe, A. White, M. Cogswell, S. Russek and A. Brooks-Kayal (2014). “The effect of STAT3 inhibition on status epilepticus and subsequent spontaneous seizures in the pilocarpine model of acquired epilepsy.” Neurobiology of Disease 62: 73-85.

Guinea-Viniegra, J., M. Jiménez, H. B. Schonthaler, R. Navarro, Y. Delgado, M. J. Concha-Garzón, E. Tschachler, S. Obad, E. Daudén and E. F. Wagner (2014). “Targeting miR-21 to treat psoriasis.” Science Translational Medicine 6(225): 225re1/1-225re1/8.

Huang, R., D. Faratian, A. H. Sims, D. Wilson, J. S. Thomas, D. J. Harrison and S. P. Langdon (2014). “Increased STAT1 signaling in endocrine-resistant breast cancer.” PloS ONE 9(4): e94226/11.

Huang, Y., X. Zhou, A. Liu, S. Li, X. Wang and L. Zhang (2014). “Signal transducer and activator of transcription-3 inhibitor WP1066 affects human tongue squamous cell carcinoma proliferation and apoptosis in vitro and in vivo.” Chinese Journal of Stomatology 49(5): 308-313.

Judd, L. M., T. R. Menheniott, H. Ling, C. B. Jackson, M. Howlett, A. Kalantzis, W. Priebe and A. S. Giraud (2014). “Inhibition of the JAK2/STAT3 pathway reduces gastric cancer growth in vitro and in vivo.” PLoS ONE 9(5): e95993.

Kong, L.-Y., J. Wei, A. S. Haider, B. D. Liebelt, X. Ling, C. A. Conrad, G. N. Fuller, N. B. Levine, W. Priebe and R. Sawaya (2014). “Therapeutic targets in subependymoma.” Journal of Neuroimmunology 277(1): 168-175.

Mielecki, M., M. Milner-Krawczyk, K. Grzelak, D. Mielecki, K. A Krzysko, B. Lesyng and W. Priebe (2014). “Analogs of Cinnamic Acid Benzyl Amide As Nonclassical Inhibitors of Activated JAK2 Kinase.” Current Cancer Drug Targets 14(7): 638-651.

Tang, Y., Z. Sun, W. Wu, J. Xing, Y. He, D. Xin and P. Han (2014). “Inhibitor of signal transducer and activator of transcription 3 (STAT3) suppresses ovarian cancer growth, migration and invasion and enhances the effect of cisplatin in vitro.” Genetics and Molecular Research: GMR 14(1): 2450-2460.

Vangala, J. R., S. Dudem, N. Jain and S. V. Kalivendi (2014). “Regulation of PSMB5 Protein and β Subunits of Mammalian Proteasome by Constitutively Activated Signal Transducer and Activator of Transcription 3 (STAT3): potential role in bortezomib-mediated anticancer therapy.” Journal of Biological Chemistry 289(18): 12612-12622.

Xue, Z.-j., L. Shen, Z.-y. Wang, S.-y. Hui, Y.-g. Huang and C. Ma (2014). “STAT3 inhibitor WP1066 as a novel therapeutic agent for bCCI neuropathic pain rats.” Brain Research 1583: 79-88.

Yuan, F., X. Fu, H. Shi, G. Chen, P. Dong and W. Zhang (2014). “Induction of Murine Macrophage M2 Polarization by Cigarette Smoke Extract via the JAK2/STAT3 Pathway.” PLoS ONE 9(9): e107063

Zheng, L., M. Zhang, J. Xue, Y. Li, Y. Nan, M. Li, J. Wang and X. Du (2014). “Effect of Angiotensin II on STAT3 mediated atrial structural remodeling.” European Review for Medical and Pharmacological Sciences 18(16): 2365-2377.

Zheng, Q., L. Han, Y. Dong, J. Tian, W. Huang, Z. Liu, X. Jia, T. Jiang, J. Zhang and X. Li (2014). “JAK2/STAT3 targeted therapy suppresses tumor invasion via disruption of the EGFRvIII/JAK2/STAT3 axis and associated focal adhesion in EGFRvIII-expressing glioblastoma.” Neuro-Oncology 16(9): 1229-1243.

Zhou, X., Y. Ren, A. Liu, L. Han, K. Zhang, S. Li, P. Li, P. Li, C. Kang and X. Wang (2014). “STAT3 inhibitor WP1066 attenuates miRNA-21 to suppress human oral squamous cell carcinoma growth in vitro and in vivo.” Oncology Reports 31(5): 2173-2180.

Zhou, X., Y. Ren, A. Liu, R. Jin, Q. Jiang, Y. Huang, L. Kong, X. Wang and Zhang (2014). “WP1066 Sensitizes Oral Squamous Cell Carcinoma Cells to Cisplatin by Targeting STAT3/miR-21 axis”. Scientific Reports 4: 7461

Ashizawa, T., H. Miyata, et al. (2013). “Effect of the STAT3 inhibitor STX-0119 on the proliferation of cancer stem-like cells derived from recurrent glioblastoma.” International Journal of Oncology 43(1): 219-227.

Gan, A. M., E. D. Butoi, et al. (2013). “Inflammatory effects of resistin on human smooth muscle cells: Up-regulation of fractalkine and its receptor, CX3CR1 expression by TLR4 and Gi-protein pathways.” Cell and Tissue Research 351(1): 161-174.

Ho, Y., S. W. Tsao, et al. (2013). “STAT3 as a therapeutic target for Epstein-Barr virus (EBV) – associated nasopharyngeal carcinoma.” Cancer Letters 330(2): 141-149.

Hu, Y., H. Chen, et al. (2013). “Deficiency of Erbin induces resistance of cervical cancer cells to anoikis in a STAT3-dependent manner.” Oncogenesis 2 (e53): 1-12.

Khurana, S. S., T. E. Riehl, et al. (2013). “The hyaluronic acid receptor CD44 coordinates normal and metaplastic gastric epithelial progenitor cell proliferation.” Journal of Biological Chemistry 288(22): 16085-16097.

Liu, F., J. Cao, et al. (2013). “Stat3-targeted therapies overcome the acquired resistance to vemurafenib in melanomas.” Journal of Investigative Dermatology 133(8): 2041-2049.

Slater, L. H., E. C. Hett, et al. (2013). “Identification of novel host-targeted compounds that protect from anthrax lethal toxin-induced cell death.” ACS Chem Biol 8(4): 812-822.

Song, B., H. Jin, et al. (2013). “Angiotensin-converting enzyme 2 attenuates oxidative stress and VSMC proliferation via the JAK2/STAT3/SOCS3 and profilin-1/MAPK signaling pathways.” Regulatory Peptides 185: 44-51.

Stechishin, O. D., H. A. Luchman, et al. (2013). “On-target JAK2/STAT3 inhibition slows disease progression in orthotopic xenografts of human glioblastoma brain tumor stem cells.” Neuro-Oncology 15(2): 198-207.

Cai, B., J. Li, et al. (2012). “microRNA‐124 Regulates Cardiomyocyte Differentiation of Bone Marrow‐Derived Mesenchymal Stem Cells Via Targeting STAT3 Signaling.” Stem Cells 30(8): 1746-1755.

Daniel, J. M., J. Dutzmann, et al. (2012). “Inhibition of STAT3 signaling prevents vascular smooth muscle cell proliferation and neointima formation.” Basic Research in Cardiology 107(3): 261.

Hatiboglu, M. A., L. Y. Kong, et al. (2012). “The tumor microenvironment expression of p-STAT3 influences the efficacy of cyclophosphamide with WP1066 in murine melanoma models.” International Journal of Cancer 131(1): 8-17.

Higuchi, S., M. Ii, et al. (2012). “Delta-opioid receptor activation promotes mesenchymal stem cell survival via PKC/STAT3 signaling pathway.” Circulation Journal 76(1): 204-212.

Jung, M., J. Rho, et al. (2012). “Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug-resistant non-small cell lung cancer cells.” Oncogene 32(2): 209-221.

Liang, J., W. Huang, et al. (2012). “Suicide Gene Reveals the Myocardial Neovascularization Role of Mesenchymal Stem Cells Overexpressing CXCR4 (MSCCXCR4).” PloS ONE 7(9): e46158.

Liu, J.-W., Y.-C. Hsu, et al. (2012). “Leukemia Inhibitory Factor-Induced Stat3 Signaling Suppresses Fibroblast Growth Factor 1-Induced Erk1/2 Activation to Inhibit the Downstream Differentiation in Mouse Embryonic Stem Cells.” Stem Cells and Development 22(8): 1190-1197.

Loh, K. C., W. I. Leong, et al. (2012). “Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway.” PloS ONE 7(5): doi:10.1371/journal.pone.0037218.

Qu, X., G. Zhuang, et al. (2012). “Induction of Bv8 Expression by granulocyte colony-stimulating factor in CD11b+Gr1+ cells: Key role of Stat3 signaling.” Journal of Biological Chemistry 287(23): 19574-19584.

Roller, D. G., M. Axelrod, et al. (2012). “Synthetic lethal screening with small-molecule inhibitors provides a pathway to rational combination therapies for melanoma.” Molecular Cancer Therapeutics 11(11): 2505-2515.

Shang, Y., X. Yang, et al. (2012). “Low amino acids affect expression of 11β-HSD2 in BeWo cells through leptin-activated JAK-STAT and MAPK pathways.” Amino Acids 42(5): 1879-1887.

Verweij, M. M., V. Sabato, et al. (2012). “STAT5 in Human Basophils: IL-3 Is Required for Its FceRI-Mediated Phosphorylation.” Cytometry Part B (Clinical Cytometry) 82B(2): 101-106.

Chiu, H. C., D. L. Chou, et al. (2011). “Suppression of Stat3 activity sensitizes gefitinib-resistant non small cell lung cancer cells.” Biochemical Pharmacology 81(11): 1263-1270.

Demyanets, S., C. Kaun, et al. (2011). “Oncostatin M-enhanced vascular endothelial growth factor expression in human vascular smooth muscle cells involves PI3K-, p38 MAPK-, Erk1/2- and STAT1/STAT3-dependent pathways and is attenuated by interferon-γ.” Basic Research in Cardiology 106(2): 217-231.

Li, Y., H. Zhang, et al. (2011). “Transactivated EGFR mediates alpha(1)-AR-induced STAT3 activation and cardiac hypertrophy.” Am J Physiol Heart Circ Physiol 301(5): H1941-1951.

Okumura, M., T. Iwakiri, et al. (2011). “Hepatocyte growth factor suppresses the anticancer effect of irinotecan by decreasing the level of active metabolite in HepG2 cells.” Biochemical Pharmacology 82(11): 1720-1730.

Peng, Z., A. Pal, et al. (2011). “Tyrphostin-like compounds with ubiquitin modulatory activity as possible therapeutic agents for multiple myeloma.” Bioorganic & Medicinal Chemistry 19(23): 7194-7204.

Wang, Y., L. Chen, et al. (2011). “Inhibition of STAT3 reverses alkylator resistance through modulation of the AKT and beta-catenin signaling pathways.” Oncol Rep 26(5): 1173-1180.

Wei, C. C., S. Ball, et al. (2011). “Two small molecule compounds, LLL12 and FLLL32, exhibit potent inhibitory activity on STAT3 in human rhabdomyosarcoma cells.” International Journal of Oncology 38(1): 279-285.

Wei, J., A. Wu, et al. (2011). “Hypoxia potentiates glioma-mediated immunosuppression.” PloS ONE 6(1).

Bill, M. A., J. R. Fuchs, et al. (2010). “The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity.” Molecular Cancer 9: 165.

Horiguchi, A., T. Asano, et al. (2010). “STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma.” British Journal of Cancer 102(11): 1592-1599.

Humphries, W., J. Wei, et al. (2010). “The Role of Tregs in Glioma-Mediated Immunosuppression: Potential Target for Intervention.” Neurosurgery Clinics of North America 21(1): 125-137.

Kong, L. Y., A. S. Wu, et al. (2010). “Intratumoral mediated immunosuppression is prognostic in genetically engineered murine models of glioma and correlates to immunotherapeutic responses.” Clinical Cancer Research 16(23): 5722-5733.

Lin, L., B. Hutzen, et al. (2010). “A novel small molecule, LLL12, inhibits STAT3 phosphorylation and activities and exhibits potent growth-suppressive activity in human cancer cells.” Neoplasia (New York, NY) 12(1): 39.

Manea, S.-A., A. Manea, et al. (2010). “Inhibition of JAK/STAT signaling pathway prevents high-glucose-induced increase in endothelin-1 synthesis in human endothelial cells.” Cell and Tissue Research 340(1): 71-79.

Shabbir, A., D. Zisa, et al. (2010). “Activation of host tissue trophic factors through JAK-STAT3 signaling: A mechanism of mesenchymal stem cell-mediated cardiac repair.” American Journal of Physiology – Heart and Circulatory Physiology 299(5): H1428-H1438.

Wei, J., J. Barr, et al. (2010). “Glioblastoma cancer-initiating cells inhibit T-cell proliferation and effector responses by the signal transducers and activators of transcription 3 pathway.” Molecular Cancer Therapeutics 9(1): 67-78.

Heimberger, A. B., L. Y. Kong, et al. (2009). “The role of tregs in human glioma patients and their inhibition with a novel STAT-3 inhibitor.” Clinical Neurosurgery 56: 98-106.

Kong, L. Y., J. Wei, et al. (2009). “A novel phosphorylated STAT3 inhibitor enhances T cell cytotoxicity against melanoma through inhibition of regulatory T cells.” Cancer Immunol Immunother 58(7): 1023-1032.

Kupferman, M. E., A. Jayakumar, et al. (2009). “Therapeutic suppression of constitutive and inducible JAK\STAT activation in head and neck squamous cell carcinoma.” Journal of Experimental Therapeutics and Oncology 8(2): 117-127.

McGaffin, K. R., B. Zou, et al. (2009). “Leptin attenuates cardiac apoptosis after chronic ischaemic injury.” Cardiovascular Research 83(2): 313-324.

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Verstovsek, S., T. Manshouri, et al. (2008). “WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation.” Clinical Cancer Research 14(3): 788-796.

Wilks, A. F. (2008). “The JAK kinases: Not just another kinase drug discovery target.” Seminars in Cell and Developmental Biology 19(4): 319-328.

Ferrajoli, A., S. Faderl, et al. (2007). “WP1066 disrupts janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells.” Cancer Research 67(23): 11291-11299.

Hussain, S. F., L. Y. Kong, et al. (2007). “A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients.” Cancer Research 67(20): 9630-9636.

Iwamaru, A., S. Szymanski, et al. (2007). “A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both in vitro and in vivo.” Oncogene 26(17): 2435-2444.

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Yokoyama, T., Y. Kondo, et al. (2007). “Roles of mTOR and STAT3 in autophagy induced by telomere 3′ overhang-specific DNA oligonucleotides.” Autophagy 3(5): 496-498.

WP1122 Bibliography

Felix, E., I. Fokt, J. Arumugam, M. Krasinski, M. Tai Khuong, R. Zielinski, S. Skora, V. Radjendirane and W. Priebe (2018). “EXTH-07. DESIGN AND EVALUATION OF WP1122, AN INHIBITOR OF GLYCOLYSIS WITH INCREASED CNS UPTAKE.” Neuro-Oncology 20(suppl_6): vi86-vi86.

Shao, B., C.-W. Li, S.-O. Lim, L. Sun, Y.-J. Lai, J. Hou, C. Liu, C.-W. Chang, Y. Qiu and J.-M. J. A. j. o. c. r. Hsu (2018). “Deglycosylation of PD-L1 by 2-deoxyglucose reverses PARP inhibitor-induced immunosuppression in triple-negative breast cancer.”  8(9): 1837.

Conrad, C. “WP1122: Novel Therapy for CNS Malignancies”, National Brain Tumor Society

https://braintumor.org/assets/docs/advanced-research/integrated-initiatives/art/anti-glycolysis-charles-conrad-overview-presentation-mdacc.pdf