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| | BML-275 Basic information |
| Product Name: | BML-275 | | Synonyms: | dorsoMorphin (Hydrochloride);DorsoMorphin, Dihydrochloride Salt, >99%;BML-275,Compound C;6-[4-[2-(1-Piperidinyl)ethoxy]phenyl]-3-(4-pyridinyl)pyrazolo[1,5-a]pyrimidine hydrochloride (1:2) Dorsomorphin 2HCl;Dorsomorphin-2HCl
BML-275;6-[4-[2-(1-Piperidinyl)ethoxy]phenyl]-3-(4-pyridinyl)pyrazolo[1,5-a]pyrimidine hydrochloride (1:2);BML-275 dihydrochloride;Dorsomorphin(BML-275)dihydrochloride | | CAS: | 1219168-18-9 | | MF: | C24H27Cl2N5O | | MW: | 472.41008 | | EINECS: | | | Product Categories: | PI3K/Akt/mTOR;Inhibitors;Akt;mTOR;PI3K | | Mol File: | 1219168-18-9.mol |  |
| | BML-275 Chemical Properties |
| storage temp. | under inert gas (nitrogen or Argon) at 2-8°C | | solubility | insoluble in EtOH; insoluble in H2O; ≥11.34 mg/mL in 0.9% NS ; ≥39.93 mg/mL in DMSO:H2O=2:1 ; ≥5.91 mg/mL in DMSO | | form | Light yellow powder solid. | | color | Yellow | | Stability: | Hygroscopic |
| | BML-275 Usage And Synthesis |
| Description | Dorsomorphin (hydrochloride) is a potent, reversible inhibitor of AMP kinase (AMPK; Ki = 109 nM) that does not exhibit significant activity on structurally related kinases, including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin can also dose-dependently inhibit the bone morphogenetic protein type 1 receptors ACTR-I (ALK2), BMPR-IA (ALK3), and BMPR-IB (ALK6). Independent of AMPK inhibition, dorsomorphin, at 10 μM, has additionally been shown to downregulate the Akt/mTOR pathway to induce autophagy in U251 human glioma cells. | | Uses | Dorsomorphin is an AMP-activated kinase (AMPK) inhibitor. Dorsomorphin selectively inhibits the bone morphogenetic protein (BMP) type I receptors ALK2, ALK3 and ALK6 and thus blocks BMP-mediated SMAD1/5/8 phosphorylation, target gene transcription and osteogenic differentiation. Dorsomorphin has shown to increase cisplatin-induced apoptosis, which was associated with hyper-induction of the tumor suppressor p53. | | in vivo | Dorsomorphin (compound C; 10 mg/kg, intravenously once) dihydrochloride treatment leads to a 60% increase in total serum iron concentrations, reduces basal levels of hepcidin expression and increases serum iron concentrations in adult mice[3].
Dorsomorphin (0.2 mg/kg, i.v., 30 min before LPS injection) dihydrochloride reduces ICAM-1 and VCAM-1 expression in LPS-injected rat aorta[4].
Dorsomorphin (25 mg/kg; i.p. injection, in male BALB/c mice) dihydrochloride treatment before lipopolysaccharide (LPS) injection significantly reduces lethality in contrast to animals treated with LPS challenge only[5]. | Animal Model: | Wild-type (WT) C57BL/6 adult mice that are fed a standard iron-replete diet express high levels of hepcidin[3]. | | Dosage: | 10 mg/kg. | | Administration: | Intravenously once. | | Result: | Led to a 60% increase in total serum iron concentrations.
Effective in reducing basal levels of hepcidin expression and increasing serum iron concentrations in adult mice.
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| Animal Model: | Male Sprague-Dawley rats, 8 weeks of age (body weight 230-250 g)[4]. | | Dosage: | 0.2 mg/kg. | | Administration: | I.V., 30 min before LPS injection. | | Result: | Reduced ICAM-1 and VCAM-1 expression in LPS-injected rat aorta. |
| Animal Model: | Male BALB/c mice at 6-7 weeks of age weighing 20-22 g[5] | | Dosage: | 25 mg/kg | | Administration: | Injection i.p.; 60 min before LPS challenge | | Result: | Treatment of mice with 25 mg/kg before LPS injection significantly reduced lethality in contrast to animals treated with LPS challenge only. |
| | IC 50 | AMPK: 109 nM (Ki); ACVR1; BMPR1A; ALK6; Autophagy | | storage | Room temperature (desiccate) | | References | [1] ZHOU G, MYERS R W, LI Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action.[J]. The Journal of clinical investigation, 2001, 1 1: 0. DOI: 10.1172/jci13505
[2] PAUL B YU. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism[J]. Nature chemical biology, 2007, 4 1: 33-41. DOI: 10.1038/nchembio.2007.54
[3] LJUBICA VUCICEVIC. Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway.[J]. Autophagy, 2011, 7 1: 40-50. DOI: 10.4161/auto.7.1.13883 |
| | BML-275 Preparation Products And Raw materials |
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