664334-36-5 Usage
Uses
Used in Anticancer Applications:
BL-8040 is used as an antineoplastic agent for its potential to inhibit the CXCR4 receptor, which is involved in tumor growth and progression. By targeting this receptor, BL-8040 may help in the treatment of various types of cancer.
Used in Stem Cell Mobilization:
BL-8040 is used as a safe and efficient stem cell mobilizer for engraftment. Its ability to inhibit the CXCR4 receptor promotes the release of stem cells from the bone marrow, facilitating their collection and transplantation in patients undergoing stem cell therapy.
Used in Drug Delivery Systems:
To overcome the limitations of BL-8040, novel drug delivery systems have been developed to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles have been employed as carriers for BL-8040 delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.
Biological Activity
bkt140, also known as bl-8040 and tf 14016, is an orally bioavailable inhibitor of cxc chemokine receptor 4 (cxcr4) with potential antineoplastic activity [1].the g protein-coupled receptor cxcr4 plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types. cxcr4 has been involved in promoting tumor progression. cxcr4 expression is a prognostic marker in various types of cancer, such as acute myelogenous leukemia or breast carcinoma. cxcr4 acts as an important molecule involved in the spread and progression of a variety of different tumors [2].bkt140 reduced the colony-forming capacity of non-small cell lung cancer (nsclc) cells. subcutaneous administration of bkt140 significantly delayed the development of h460 xenografts and showed a similar trend for a549 xenografts [1]. pre-clinical studies in animal models with bkt140 showed a robust mobilization of white blood cells (wbc) and hematopoietic stem cells (hsc). bkt140 showed a direct anti-tumor effect against human-derived multiple myeloma (mm), lymphoma and primary leukemia cells and cell lines in vitro and in vivo, causing significant apoptosis [2]. bkt140 was well tolerated and rapidly absorbed in patients with multiple myeloma. bkt140 administration significantly increased the number of peripheral blood neutrophils, monocytes, lymphocytes, and cd34+ cells in a dose-dependent manner [3].
Enzyme inhibitor
This orally bioavailable, disulfide cross-linked, polyphemusin-II-derived peptide antagonist (sequence shown above, with Nal = naphthylamine, Cit = citrulline, D-Lys = D-Lysine, and Cys = half-cystine), also known as 4-Fbenzoyl-TN14003 and BL-8040, targets CXC Chemokine Receptor-4 (CXCR4), a G-protein-coupled receptor that is directly involved in tumor progression, tumor angiogenesis, metastasis, and cancer cell survival. Primary Mode of Inhibitory Action: CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. BKT140 exhibits high affinity (Ki = 0.8nM) and a low rate of dissociation from its receptor. BKT140 prevents the binding of stromal derived factor-1 (SDF-1 or CXCL12) to CXCR4 activation, resulting in decreased tumor cell proliferation and migration. In addition, inhibition of CXCR4 may mobilize hematopoietic cell egress from the bone marrow and into blood. BKT140 significantly and preferentially stimulates multiple myeloma apoptotic cell death, as indicated by induced morphological changes, phosphatidylserine externalization, decreased mitochondrial membrane potential, caspase-3 activation, sub-G1 cell-cycle arrest, as well as DNA double-stranded breaks.
references
[1] fahham d, weiss i d, abraham m, et al. in vitro and in vivo therapeutic efficacy of cxcr4 antagonist bkt140 against human non–small cell lung cancer[j]. the journal of thoracic and cardiovascular surgery, 2012, 144(5): 1167-1175. e1.[2] burger j a, kipps t j. cxcr4: a key receptor in the crosstalk between tumor cells and their microenvironment[j]. blood, 2006, 107(5): 1761-1767.[3] nagler a, shimoni a, avivi i, et al. bkt140 is a novel cxcr4 antagonist with stem cell mobilization and antimyeloma effects: an open-label first human trial in patients with multiple myeloma undergoing stem cell mobilization for autologous transplantation[j]. blood, 2010, 116(21): 2260-2260.
Check Digit Verification of cas no
The CAS Registry Mumber 664334-36-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 6,6,4,3,3 and 4 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 664334-36:
(8*6)+(7*6)+(6*4)+(5*3)+(4*3)+(3*4)+(2*3)+(1*6)=165
165 % 10 = 5
So 664334-36-5 is a valid CAS Registry Number.
664334-36-5Relevant academic research and scientific papers
Hennrich, Ute,Seyler, Lisa,Sch?fer, Martin,Bauder-Wüst, Ulrike,Eisenhut, Michael,Semmler, Wolfhard,B?uerle, Tobias
, p. 1502 - 1510 (2012)
The expression of the chemokine receptor CXCR4 in tumors is associated with tumor aggressiveness and poor prognosis for the patient and contributes to metastatic seeding. Therefore it is of high interest to find a specific PET tracer for the imaging of CX
