Blosozumab
目录号 : GC66384
Blosozumab (LY2541546) 是一种抗人 sclerostin (SOST) 的抗体抑制剂。Blosozumab 可刺激骨形成并减少骨吸收。Blosozumab 可用于骨质疏松症的研究。
Cas No.:1132758-87-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
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Blosozumab (LY2541546) is an anti-Human sclerostin (SOST) antibody inhibitor. Blosozumab stimulates bone formation and reduces bone resorption. Blosozumab can be used in the research of Osteoporosis[1][2].
Blosozumab (1-100 mg/kg, i.v.) shows effects of hyperostosis in rats[1].
| Animal Model: | Sprague-Dawley rats [2] |
| Dosage: | 1, 10, and 100 mg/kg |
| Administration: | Intravenous injection (i.v.), once every 3 days (5-week study) or once weekly (6-month study) |
| Result: | Observed the bone anabolic effects. Showed significant bleeding and morbidity at 100 mg/kg. Decreases in the numbers of platelets. Increased number of bone marrow megakaryocytes at 100 mg/kg. |
| Cas No. | 1132758-87-2 | SDF | Download SDF |
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Blosozumab in the treatment of postmenopausal women with osteoporosis: a systematic review and meta-analysis
Ann Palliat Med 2022 Oct;11(10):3203-3212.PMID:36367007DOI:10.21037/apm-22-998.
Background: Postmenopausal women are one of the most vulnerable groups to osteoporosis. Romosozumab is a newly monoclonal drug that inhibits the activity of sclerostin. Since it has been on the market for only 3 years, there is a lack of systematic analysis on postmenopausal women and the efficacy is not clear. In this study, we compared randomized controlled trials to assess the effects of Blosozumab versus placebo in perimenopausal and postmenopausal women. Methods: This meta-analysis has been registered in the PROSPERO registry (number CRD42020145839). The PubMed, Cochrane Library, ClinicalKey, and Embase databases were searched from inception date to July 01, 2021. We used the keywords "osteoporosis", "decreased bone mass", and "Blosozumab" to retrieve studies on the relationship between Blosozumab and osteoporosis in each database. The inclusion criteria were: (I) randomized controlled trials (RCTs) comparing the treatment of osteoporosis with Blosozumab and a placebo or without treatment, (II) studies on postmenopausal women aged over 50 years, and (III) studies providing bone mineral density data. The quality of all randomized controlled trials included in this study was independently assessed by two researchers according to the Cochrane risk manual and was divided into high, medium and low quality. The main results analyzed were bone mineral density (BMD) and T-score. Our results mainly include BMD and procollagen type I N-terminal propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC). Results: Three RCTs with 105 patients were selected from 157 retrieved articles. Due to high heterogeneity [BMD: Tau2=2.79; Chi2=11.70, degrees of freedom (df) =1 (P=0.0006); I2=91%], we could not perform statistical analysis of BMD. The results of BMD were then evaluated systematically. Three RCT studies were included in the evaluation. Compared with that of the placebo, Blosozumab increased levels of the BMD biomarker osteocalcin [mean deviation (MD) 12.55; 95% confidence interval (CI), 8.18, 16.91; P<0.00001]. None of the 3 RCTs presented a risk of bias during the meta-analysis. Conclusions: The results suggested that Blosozumab could be used as a target drug to improve BMD in postmenopausal women. This will provide a reference for the clinical treatment of postmenopausal women with osteoporosis.
Targeting Sclerostin in Postmenopausal Osteoporosis: Focus on Romosozumab and Blosozumab
BioDrugs 2017 Aug;31(4):289-297.PMID:28547661DOI:10.1007/s40259-017-0229-2.
Most current treatments for osteoporosis inhibit bone resorption and reduce total fracture numbers by about one-quarter. The identification of the osteocytic protein sclerostin as a potent regulator of bone turnover and bone density has led to the development of a new therapeutic class-agents that inhibit sclerostin activity, resulting in increased bone formation and reduced bone resorption. Romosozumab and Blosozumab are monoclonal antibodies that bind to sclerostin, reducing its inhibition of Wnt signaling. They have comparable activities in phase I and II studies, doubling formation markers, halving resorption indices, and increasing spine bone density by >10% over 12 months. Only romosozumab has progressed to phase III, where the first study showed a 73% reduction in vertebral fracture risk and a 36% reduction in clinical fractures at 1 year. It was well-tolerated. A further phase III study will conclude in 2017. Romosozumab is a very promising medication in the management of established osteoporosis, but much remains to be done to determine its optimal duration and sequence of administration.
Molecular genetics and targeted therapy of WNT-related human diseases (Review)
Int J Mol Med 2017 Sep;40(3):587-606.PMID:28731148DOI:10.3892/ijmm.2017.3071.
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription. Germline mutations in WNT signaling molecules cause hereditary colorectal cancer, bone diseases, exudative vitreoretinopathy, intellectual disability syndrome and PCP-related diseases. APC or CTNNB1 mutations in colorectal, endometrial and prostate cancers activate the WNT/β-catenin signaling cascade. RNF43, ZNRF3, RSPO2 or RSPO3 alterations in breast, colorectal, gastric, pancreatic and other cancers activate the WNT/β-catenin, WNT/STOP and other WNT signaling cascades. ROR1 upregulation in B-cell leukemia and solid tumors and ROR2 upregulation in melanoma induce invasion, metastasis and therapeutic resistance through Rho-ROCK, Rac-JNK, PI3K-AKT and YAP signaling activation. WNT signaling in cancer, stromal and immune cells dynamically orchestrate immune evasion and antitumor immunity in a cell context-dependent manner. Porcupine (PORCN), RSPO3, WNT2B, FZD5, FZD10, ROR1, tankyrase and β-catenin are targets of anti-WNT signaling therapy, and ETC-159, LGK974, OMP-18R5 (vantictumab), OMP-54F28 (ipafricept), OMP-131R10 (rosmantuzumab), PRI-724 and UC-961 (cirmtuzumab) are in clinical trials for cancer patients. Different classes of anti-WNT signaling therapeutics are necessary for the treatment of APC/CTNNB1-, RNF43/ZNRF3/RSPO2/RSPO3- and ROR1-types of human cancers. By contrast, Dickkopf-related protein 1 (DKK1), SOST and glycogen synthase kinase 3β (GSK3β) are targets of pro-WNT signaling therapy, and anti-DKK1 (BHQ880 and DKN-01) and anti-SOST (Blosozumab, BPS804 and romosozumab) monoclonal antibodies are being tested in clinical trials for cancer patients and osteoporotic post-menopausal women. WNT-targeting therapeutics have also been applied as reagents for in vitro stem-cell processing in the field of regenerative medicine.
The Effect of Discontinuing Treatment With Blosozumab: Follow-up Results of a Phase 2 Randomized Clinical Trial in Postmenopausal Women With Low Bone Mineral Density
J Bone Miner Res 2015 Sep;30(9):1717-25.PMID:25707611DOI:10.1002/jbmr.2489.
Administration of Blosozumab, a humanized monoclonal antibody that binds sclerostin, increases bone formation and bone mineral density (BMD) in postmenopausal women with low BMD. To evaluate the effect of discontinuing Blosozumab, we studied women enrolled in a 1-year randomized, placebo-controlled phase 2 trial for an additional year after they completed treatment. Of the 120 women initially enrolled in the study, 106 women completed treatment and continued into follow-up; 88 women completed 1 year of follow-up. At the beginning of follow-up, groups remained balanced for age, race, and body mass index, but lumbar spine and total hip BMD were increased in prior Blosozumab groups, reflecting an anabolic treatment effect. At the end of follow-up, 1 year after discontinuing treatment, lumbar spine BMD remained significantly greater than placebo in women initially treated with Blosozumab 270 mg every 2 weeks (Q2W) and Blosozumab 180 mg Q2W (6.9% and 3.6% above baseline, respectively). Total hip BMD also declined after discontinuation of treatment but at 1 year after treatment remained significantly greater than placebo in women initially treated with Blosozumab 270 mg Q2W and Blosozumab 180 mg Q2W (3.9% and 2.6% above baseline, respectively). During follow-up, median serum P1NP was not consistently different between the prior Blosozumab groups and placebo. A similar pattern was apparent for median serum C-terminal telopeptide of type 1 collagen (CTx) levels, with more variability. Mean serum total sclerostin concentration increased with Blosozumab, indicating target engagement, and declined to baseline after discontinuation. There were no adverse events considered related to prior treatment with Blosozumab. Anti-drug antibodies generally declined in patients who had detectable levels during prior treatment. These findings support the continued study of Blosozumab as an anabolic therapy for treatment of osteoporosis.
Single- and multiple-dose randomized studies of Blosozumab, a monoclonal antibody against sclerostin, in healthy postmenopausal women
J Bone Miner Res 2014 Apr;29(4):935-43.PMID:23996473DOI:10.1002/jbmr.2092.
Two clinical studies were conducted to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses (intravenous [iv] and subcutaneous [sc]) of Blosozumab in postmenopausal women, including prior/current bisphosphonate (BP) users. In these phase 1, randomized, subject- and investigator-blind, placebo-controlled studies, subjects received escalating doses of Blosozumab: single iv doses up to 750 mg, single sc doses of 150 mg, multiple iv doses up to 750 mg every 2 weeks (Q2W) for 8 weeks, multiple sc doses up to 270 mg Q2W for 8 weeks, or placebo. Six subjects were randomized to each dose in the single-dose study (12 to placebo) and up to 12 subjects to each arm in the multiple-dose study. Blosozumab was well tolerated with no safety concerns identified after single or multiple administrations up to 750 mg. Dose-dependent responses were observed in sclerostin, N-terminal propeptide of procollagen type 1, bone-specific alkaline phosphatase, osteocalcin, C-terminal fragment of type 1 collagen, and bone mineral density (BMD) after single and multiple (up to 5) administrations of Blosozumab. There was up to a 3.41% (p=0.002) and up to a 7.71% (p<0.001) change from baseline in lumbar spine BMD at day 85 after single or multiple administrations of Blosozumab, respectively. Prior BP use did not appear to have a clear impact on the effects of single doses of Blosozumab when considering bone biomarker and BMD responses. Antibodies to Blosozumab were detected by a screening assay, but no patterns with regard to dose or route of administration and no clear impact on Blosozumab exposure or PD responses were identified. In summary, Blosozumab was well tolerated and exhibited anabolic effects on bone. These findings support further investigation of Blosozumab as a potential anabolic therapy for osteoporosis.