BLU-782 (Synonyms: Activin Receptor-like Kinase 2 Inhibitor 1, ALK2-IN-1, Fidrisertib) |
| Catalog No.GC19508 |
BLU-782 is an oral precision therapy specifically designed to selectively target mutant ALK2.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2141955-96-4
Sample solution is provided at 25 µL, 10mM.
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BLU-782 is an oral precision therapy specifically designed to selectively target mutant ALK2[1].
FOP is a rare genetic disorder characterized by the abnormal transformation of skeletal muscle, ligaments and tendons into bone, either spontaneously or as the result of physical trauma. FOP is caused by a mutation in the gene for ALK2, which is known as ACVR1, that causes hypersensitivity to certain bone morphogenetic proteins (BMP) and a neomorphic response to activins[4,5].
BLU-782 demonstrated exquisite selectivity for R206H mutant ALK2 in cellular assays, while sparing closely related anti-targets including ALK1, ALK3, and ALK6. Additionally, BLU-782 potently inhibited mutant ALK2 in vitro, regardless of the activating ligand, including Activin A, Activin B and BMP6. In vivo studies in a conditional knock-in ALK2R206H transgenic mouse model showed BLU-782 prevented the formation of injury-induced HO and edema, as measured by micro computed tomography and magnetic resonance imaging. Immunohistochemistry analyses also showed restoration of a healthy response to tissue injury in ALK2R206H mice, including skeletal myofiber regeneration. In addition, BLU-782 prevented the formation of surgery-induced HO following fibular osteotomy surgery in ALK2R206H mice[1]. BLU-782 dampens edema early and prevents HO in ALK2R206H mice[7].
The Phase I clinical trial BLU-782 in healthy volunteers to establish its safety of the investigational drug was recently completed (NCT03858075), and the result showed that BLU-782 is well tolerated with approximately 24 h of half-life and displays excellent properties of pharmacokinetics and pharmacodynamics[2,3].
Blu-782 selectively targets only mutant ALK2 with minimal interference to wild-type ALK2, which may be a good strategy for future FOP therapy[6].
References:
[1]: Blueprint medicines presents foundational preclinical data supporting the development of BLU-782, a highly selective ALK2 inhibitor, for the treatment of patients with fibrodysplasia ossificans progressive (2018)
[2]: Safety, tolerability, pharmacokinetics, and food effect of BLU-782 in healthy adults (2019). https://clinicaltrials.gov/ct2/show/NCT03858075. Accessed 14 Dec 2021
[3]: Alison DFA, Riadh L, Michael P, Cori AS, Sara G, Faith S, Sean K, Gordon W, Mark H, Robert S, Rachel S, Morgan L, Pauplis R, Vivek K, Andy B, Timothy L (2019) A clinical update on BLU-782, an investigational ALK2 inhibitor in development for fibrodysplasia ossificans progressiva (FOP). https://www.blueprintmedicines.com/wp-content/uploads/2019/09/Blueprint-Medicines-ASBMR-2019-BLU-782-Poster1.pdf.
[4]: Towler OW, Shore EM. BMP signaling and skeletal development in fibrodysplasia ossificans progressiva (FOP). Dev Dyn. 2022 Jan;251(1):164-177. doi: 10.1002/dvdy.387. Epub 2021 Jun 26. PMID: 34133058; PMCID: PMC9068236.
[5]: Kaplan FS, Xu M, Seemann P, Connor JM, Glaser DL, Carroll L, Delai P, Fastnacht-Urban E, Forman SJ, Gillessen-Kaesbach G, Hoover-Fong J, KÖster B, Pauli RM, Reardon W, Zaidi SA, Zasloff M, Morhart R, Mundlos S, Groppe J, Shore EM. Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat. 2009 Mar;30(3):379-90. doi: 10.1002/humu.20868. PMID: 19085907; PMCID: PMC2921861.
[6]: Meng, X., Wang, H. & Hao, J. Recent progress in drug development for fibrodysplasia ossificans progressiva. Mol Cell Biochem 477, 2327-2334 (2022). https://doi.org/10.1007/s11010-022-04446-9
[7]: A clinical update on BLU-782, an investigational ALK2 inhibitor in development for fibrodysplasia ossificans progressiva (FOP)
| Animal experiment [1]: | |
Animal models | ALK2R206H mice |
Preparation Method | WT or ALK2R206H mice were untreated or dosed prophylactically with BLU-782 before receiving a pinch injury to one leg. |
Dosage form | 50 mpk QD BLU-782 for 19days |
Applications | BLU-782 dampens edema early and prevents HO in ALK2R206H mice. |
References: | |
| Cas No. | 2141955-96-4 | SDF | |
| Synonyms | Activin Receptor-like Kinase 2 Inhibitor 1, ALK2-IN-1, Fidrisertib | ||
| Chemical Name | 1-Piperazinecarboxylic acid, 4-[6-[5-[4-ethoxy-1-(1-methylethyl)-4-piperidinyl]-2-pyridinyl]pyrrolo[1,2-b]pyridazin-4-yl]-, (3R)-tetrahydro-3-furanyl ester | ||
| Canonical SMILES | O=C(N1CCN(C2=CC=NN3C2=CC(C4=NC=C(C5(OCC)CCN(C(C)C)CC5)C=C4)=C3)CC1)O[C@H]6COCC6 | ||
| Formula | C31H42N6O4 | M.Wt | 562.715 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.7771 mL | 8.8855 mL | 17.771 mL |
| 5 mM | 0.3554 mL | 1.7771 mL | 3.5542 mL |
| 10 mM | 0.1777 mL | 0.8885 mL | 1.7771 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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