以色列生物医药公司BioLineRx公司最近在Molecular Cancer Therapeutics杂志上披露了其治疗慢性白血病的新药BL-8040的临床前研究数据。在动物学实验和小鼠实验中，BL-8040单独使用和与imatinib联合使用都表现出良好效果。以imatinib为代表的酪氨酸激酶抑制剂是常见的白血病药物，但是很多白血病患者表现出对酪氨酸激酶抑制剂抗性，使得医疗上急切希望有新的白血病药物出现。当BL-8040与低剂量imatinib联合使用时表现出协同作用，对小鼠肿瘤生长抑制率达到95%。BL-8040是一种CXCR4拮抗剂，CXCR4是一种趋化因子受体，高表达时能够导致癌症的发生。BL-8040通过阻断这种受体来促进细胞程序性死亡，从而达到治疗白血病的目的。
BioLineRx公司希望于今年第二季度开始对BL-8040的临床一期研究。
正大天晴2013年6月10日与BioLineRx达成协议，正大天晴支付BioLineRx 3000万美元，获得化合物BL-8030在中国和香港地区的权利。BL-8030是第二代NS3蛋白酶抑制剂，目前处于临床前研究阶段。
BioLineRx (BLRX) Announces Positve Study on BL-8040 in Molecular Cancer Therapeutics
BioLineRx (NASDAQ: BLRX) announced today positive pre-clinical results for BL-8040 in a third indication - as a treatment for chronic myeloid leukemia. Results of the study were recently published in Molecular Cancer Therapeutics.
Chronic myeloid leukemia (CML) is a cancer of white blood cells that is driven by a constitutively active oncogenic tyrosine kinase. Tyrosine kinase inhibitors, such as imatinib mesylate (Gleevec), revolutionized the treatment of CML and remain a major therapeutic strategy for CML patients. However, dormant leukemic stem cells that are resistant to tyrosine kinase inhibitors and may be responsible for CML resistance and recurrence, are protected from therapy-induced cell death by the bone marrow microenvironment and in particular, by bone marrow stromal cells. Therefore, novel drugs are needed that can target leukemic stem cells in the bone marrow.
The study, led by Prof. Arnon Nagler, Director of the Hematology Division and Bone Marrow Transplantation Center at Sheba Medical Center, Israel, assessed the effect of BL-8040 alone, and in combination with imatinib, on the proliferation of human CML cells in culture and on human CML tumors that were engrafted in mice. Results of the study show that the BL-8040 treatment directly inhibited cancer cell growth and induced apoptotic cell death of CML cells in-vitro. Furthermore, BL-8040 had a synergistic effect with imatinib, enabling use of imatinib at low doses. In mice engrafted with CML tumors, the combination of BL-8040 with low-dose imatinib markedly inhibited tumor growth, achieving a 95% suppression. Most importantly, the novel drug reversed the protective effect of the bone marrow stroma on CML cells, effectively promoting their apoptosis.
"We are very pleased with the results of this study, which show that BL-8040 has the potential to be an important addition to the drug arsenal for CML," stated Prof. Nagler. "BL-8040 shows two intriguing properties. First, it can directly suppress CML cell proliferation, and second, it can sensitize CML cells that hide in the bone marrow to therapy-induced apoptosis. The second property mainly stems from the ability of this drug to flush out cancer cells from the bone marrow into the peripheral blood."
Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx, commented, "These encouraging results support the rationale for BL-8040 therapy, in combination with tyrosine kinase inhibitors, to override drug resistance and suppress residual disease. The study shows that BL-8040 has the potential to treat CML patients who have developed resistance to Gleevec. BL-8040 is currently undergoing a Phase 2 trial for AML and is expected to enter a Phase 1 trial for stem cell mobilization in the second quarter of this year, with top-line results for both of these studies expected in the fourth quarter of 2014. We have high hopes that this promising drug will realize its potential to help cancer patients, both as a stand-alone therapy and in combination with other therapies in the foreseeable future."BioLineRx (NASDAQ: BLRX) announced today positive pre-clinical results for BL-8040 in a third indication - as a treatment for chronic myeloid leukemia. Results of the study were recently published in Molecular Cancer Therapeutics.
Chronic myeloid leukemia (CML) is a cancer of white blood cells that is driven by a constitutively active oncogenic tyrosine kinase. Tyrosine kinase inhibitors, such as imatinib mesylate (Gleevec), revolutionized the treatment of CML and remain a major therapeutic strategy for CML patients. However, dormant leukemic stem cells that are resistant to tyrosine kinase inhibitors and may be responsible for CML resistance and recurrence, are protected from therapy-induced cell death by the bone marrow microenvironment and in particular, by bone marrow stromal cells. Therefore, novel drugs are needed that can target leukemic stem cells in the bone marrow.
The study, led by Prof. Arnon Nagler, Director of the Hematology Division and Bone Marrow Transplantation Center at Sheba Medical Center, Israel, assessed the effect of BL-8040 alone, and in combination with imatinib, on the proliferation of human CML cells in culture and on human CML tumors that were engrafted in mice. Results of the study show that the BL-8040 treatment directly inhibited cancer cell growth and induced apoptotic cell death of CML cells in-vitro. Furthermore, BL-8040 had a synergistic effect with imatinib, enabling use of imatinib at low doses. In mice engrafted with CML tumors, the combination of BL-8040 with low-dose imatinib markedly inhibited tumor growth, achieving a 95% suppression. Most importantly, the novel drug reversed the protective effect of the bone marrow stroma on CML cells, effectively promoting their apoptosis.
"We are very pleased with the results of this study, which show that BL-8040 has the potential to be an important addition to the drug arsenal for CML," stated Prof. Nagler. "BL-8040 shows two intriguing properties. First, it can directly suppress CML cell proliferation, and second, it can sensitize CML cells that hide in the bone marrow to therapy-induced apoptosis. The second property mainly stems from the ability of this drug to flush out cancer cells from the bone marrow into the peripheral blood."
Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx, commented, "These encouraging results support the rationale for BL-8040 therapy, in combination with tyrosine kinase inhibitors, to override drug resistance and suppress residual disease. The study shows that BL-8040 has the potential to treat CML patients who have developed resistance to Gleevec. BL-8040 is currently undergoing a Phase 2 trial for AML and is expected to enter a Phase 1 trial for stem cell mobilization in the second quarter of this year, with top-line results for both of these studies expected in the fourth quarter of 2014. We have high hopes that this promising drug will realize its potential to help cancer patients, both as a stand-alone therapy and in combination with other therapies in the foreseeable future."
关键词： BioLineRx 慢性白血病 新药 BL-8040 药理 临床前研究
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