Dorsomorphin [866405-64-3]

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Dorsomorphin (Compound C) is a selective and ATP-competitive AMPK inhibitor (Ki=109 nM in the absence of AMP). Dorsomorphin (BML-275) selectively inhibits BMP type I receptors ALK2, ALK3, and ALK6. Dorsomorphin can reverse autophagy activation and anti-inflammatory effect of Urolithin A (HY-100599).

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Dorsomorphin Chemical Structure

Dorsomorphin Chemical Structure

CAS No. : 866405-64-3

This product is a controlled substance and not for sale in your territory.

Based on 555 publication(s) in Google Scholar

Other Forms of Dorsomorphin:

  • Dorsomorphin dihydrochloride In-stock
  • Dorsomorphin dihydrochloride (GMP) Obtenir un devis

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Life Sci. 2019 Jul 15;229:46-56.  [Abstract]

    Expression of APOE and COX5A in HUVECs treated with or without rhIL-17A (50 ng/mL) and Compound C (5 μM) is measured by western blot.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Redox Biol. 2018 Jul;17:180-191.  [Abstract]

    MDA-MB-231 cells are cultured in poly-HEMA coated dishes and treated with Compound C or GL-V9 for 36 h. The expression of AMPK and p-AMPK in Compound C treated cells are assayed by Western blotting.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Redox Biol. 2018 Oct;19:339-353.  [Abstract]

    Western blotting assay of AMPK, p-AMPK, PGC-1α, p-PGC-1α levels in nucleus pulposus (NP) cells stimulated with AGEs (200 μg/mL) in the presence or absence of A-769662 (50 μM), RAGE antibody (10 μg/mL), nicotinamide mononucleotide (NMN, 100 μM) or Compound C (50 uM).

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Biomed Pharmacother. 2018 Oct;106:1390-1395.  [Abstract]

    Effect of Compound C on the AMPK/Foxo1/miR-143-3p axis in Ang II-treated H9c2 cells.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Biomed Pharmacother. 2018 Oct;106:1390-1395.  [Abstract]

    Effect of Compound C on cell viability, cell surface area, and apoptosis in Ang II-treated H9c2 cells.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Biomed Pharmacother. 2018 Feb 19;100:417-425.  [Abstract]

    HaCaT cells are pre-incubated with Compound C (CC) (10 μM) and U0126 (10 μM), pharmacological inhibitors of AMPKα, ERK, respectively, for 1 h before treatment with DA8 and DA14 (DAs).

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Liver Int. 2018 Dec;38(12):2248-2259.  [Abstract]

    Cells are treated with 5 μM Dorsomorphin dihydrochloride (Compound C) for 3 hours to inhibit AMPK activity. Next, 2.5 μM CTD is applied for 24 hours. Cells are then collected for apoptosis assays and western blotting.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: J Agric Food Chem. 2018 Nov 7;66(44):11757-11766.  [Abstract]

    The number of GFP-LC3 dots are reduced significantly after inhibiting STAT3 (AG-490) signaling.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: J Agric Food Chem. 2018 Jul 5;66(26):6772-6781.  [Abstract]

    Effects of Compound C on capsiate-treated HepG2 cells in high fat environment. The expressions of key metabolic regulators and lipid metabolism-related proteins are quantified by densitometry, and the relative intensities are expressed in the bar chart.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: J Agric Food Chem. 2018 Jul 5;66(26):6772-6781.  [Abstract]

    Effects of Compound C on capsiate-treated HepG2 cells in high fat environment. The expressions of glucose metabolism-related proteins are quantified by densitometry, and the relative intensities are expressed in the bar chart.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Front Pharmacol. 2018 Aug 29;9:986.  [Abstract]

    AMPK and p38 phosphorylation is confirmed after Compound C (CC) and SB203580 treatment of Gomisin A (G.A)-treated CT26 cells.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: J Cell Physiol. 2018 Dec;233(12):9701-9715.  [Abstract]

    HUVECs are pretreated with Compound C (5, 10, or 20 μM) for 18 hr or AICAR (1, 2, or 4 mM) for 1 hr, and then exposed to LSS for 30 min.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Front Pharmacol. 2018 Feb 5;9:68.  [Abstract]

    CT26 cells are treated with CC for 4 h and detected phosphorylation levels of AMPK.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: J Cell Physiol. 2018 May;233(5):3945-3954.  [Abstract]

    Fraxinellone-prompted phosphorylation of AMPK is blocked by Compound C (CC).

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Front Pharmacol. 2018 Jul 16;9:761.  [Abstract]

    Epithelial cells from colon tissue are extracted from mice in each group (n=6-8 per group) and protein level of p-AMPK (Thr172) and AMPKα1/2 are measured by western blot.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Int J Mol Med. 2018 May;41(5):2535-2544.  [Abstract]

    Cells are treated with AICAR and AICAR (A++, 10 μM) + Compound C (C++, 1 μM) for 24 h, after which western blot analysis is performed.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: J Am Heart Assoc. 2018 Jun 12;7(12). pii: e008389.  [Abstract]

    Representative photomicrographs of immunohistochemistry for MAP2, Nissl, Iba-1, and GFAP in the hippocampal CA1 region of the sham-operated, sham-treated with Met (Met-a), and the experimental groups (Veh, Mettreated group, compound C [Cc]–treated group, Met+Cc-treated group, CQ–treated group, and Met+CQ-treated group) at 7 days after return of spontaneous circulation.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: J Am Heart Assoc. 2018 Jun 12;7(12). pii: e008389.  [Abstract]

    Representative immunoblots of LC3 in Hippo and cortical brain tissue after CA/CPR. β-Actin serves as a loading control. J, Optical densities of LC3-II and LC3-I protein bands are quantitated. Cc indicates compound C.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: J Immunol Res. 2018 Dec 24;2018:9807139.  [Abstract]

    Western blot analysis of p-AMPK, AMPK, Bcl2 and Bax, LC3B and P62 expression in liver tissues.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Acta Biochim Biophys Sin (Shanghai). 2018 Feb 1;50(2):144-155.  [Abstract]

    Raw264.7 macrophages with serum deprivation are treated with 50 μM Rg1 for 48 h in absence or presence of compound C (10 mM) or AICAR (250 μM). Western blots of the protein expressions of Atg5, Beclin1, LC3, and p62/SQSMT1.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: PLoS One. 2018 Aug 1;13(8):e0200897.  [Abstract]

    Phosphorylation of AMPK (Thr172) in HTOZ cells pretreated with Compound C at different concentrations (0-20 μM) for 1 hour prior to the presence of norUDCA at 200 μM for additional 1 hour is determined by western blotting analyses.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2018 Sep 5;503(2):428-435.  [Abstract]

    Western blotting showing AMPK/m-TOR/ULK1 pathway relative protein (AMPK, p-AMPK, mTOR, p-mTOR, ULK1 and p-ULK1) levels in low glucose (LG), LG+Compound C (CC), HG and HG+CC groups.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Med Sci Monit. 2018 Jul 25;24:5168-5177.  [Abstract]

    The levels of p-S6K and S6K in 16HBE cells after treatment of BRL 49653/Troglitazone or/and Compound C are detected by western blot. The levels of p62 and LC3 in 16HBE cells after treatment of BRL 49653/Troglitazone or/and Compound C are detected by western blot.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: J Cardiovasc Pharmacol. 2018 Oct;72(4):167-175.  [Abstract]

    Foam cells are incubated with or without Compound C (10 μM) before the addition of CTRP9. According to the Western blot, the relative protein levels of p-AMPK, p-mTOR, LC3 II, and p62 are analyzed, respectively.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Cell Physiol Biochem. 2018;50(5):1891-1902.  [Abstract]

    AMPK inhibitor dorsomorphin treatment reduces the protein expression of PGC-1α.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Cell Physiol Biochem. 2018;48(1):227-236.  [Abstract]

    Inhibition of AMPK with Compound C (CC) attenuates the protective effects of FNDC5 on the oxLDL-induced AMPK dephosphorylation and fibrosis in LX-2 cells.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2017 May 18;8(5):e2798.  [Abstract]

    Involvement of the AMPK/AKT/GSK3β pathway in Nrf2 nuclear translocation by Betulin. Cells are treated with 3 μM compound C (Comp.C) for 18 h before treatment with betulin (36 μM) for 6 h. Cell lysates are immunoblotted for the phosphorylation of AMPK, Akt, GSK3β and Nrf2.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Mol Oncol. 2017 Aug;11(8):1035-1049.  [Abstract]

    Inhibition of AMPK reverses PD 0332991-induced autophagy and apoptosis. Hep3B cells are incubated with AMPK inhibitor (Compound C, 2.5 μM) for 4 h and then treated with PD 0332991 for 24 h. Apoptotic cells are determined by flow cytometry.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Biochem Pharmacol. 2017 Aug 15;138:49-60.  [Abstract]

    Blockade of AMPK signals by AMPK α2 siRNA or AMPK inhibitor (Dorsomorphin; 2.5 μM, pretreatment 2 hours) treatment counteracts the apoptotic effects of Cantharidin at 2.5 μM. Data are representative of at least two independent experiments. Blocking AMPK signaling by knockdown of AMPK or Dorsomorphin (AMPK kinase inhibitor) treatment markedly reverses the apoptotic effect of Cantharidin, indicating that AMPK activation is required for the anti-HCC activity of Cantharidin.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Am J Chin Med. 2017;45(6):1309-1325.  [Abstract]

    Activity of MMP-2 and MMP-9 in water extract (WAF)- and ethanol extract (EtAF)-treated CT26 cells after CC (20 μM) pretreatment for 4 h.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Int J Mol Sci. 2017 May 19;18(5). pii: E1063.  [Abstract]

    Inhibition of sirt1 and AMPK blocked Rb2-induced hepatic autophagy. HepG2 cells are pretreated with 50 µM Rb2 for 4 h in the presence or absence of the sirt1 inhibitor EX-528 (EX) and the specific AMPK inhibitor Compound C (CC), and then subjected to OA (1 mM for HepG2 and 2 mM for primary mouse hepatocytes) exposure for 12 h. For lipid content determination, intracellular TG are stained by Oil red O (ORO). ORO is then eluted with isopropanol and the optical absorbance of the eluate is measured

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Free Radic Biol Med. 2016 Nov 9;101:401-412.  [Abstract]

    Effect of EsA on AMPK activation is necessary for AKT/GSK3β-mediated Nrf2 activity and cytoprotection. Cells are treated with 3 μM Compound C for 18 h, followed by treatment with EsA for 6 h, and then cell lysates are immunoblotted to assess the phosphorylation of AMPK, Akt and GSK3β and Nrf2.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Biochem Pharmacol. 2016 Dec 15;122:42-61.  [Abstract]

    Inhibition of SREBPs processing by AHI is dependent on LKB-1/AMPK/mTOR pathway. (A) HepG2 cells are incubated with or without MHY1485 or Rapamycin for 1 h, the cells are switched to medium D in the presence of vehicle, or AHI. (B) HepG2 cells are incubated with or without Compound C for 1 h, the cells are switched to medium D in the presence of vehicle, or AHI.

    Dorsomorphin purchased from MedChemExpress. Usage Cited in: Oncotarget. 2016 Apr 5;7(14):18085-94.  [Abstract]

    MACC1 is up-regulated by ACh through p-AMPK. A. ACh stimulates AMPK phosphorylation via M3R. B. Inhibition of AMPK activity by Dorsomorphin (8 μM) suppresses the induction of MACC1 expression by ACh. p-AMPK levels increase after ACh stimulation, and pretreatment of UK-88525 attenuates the ACh-induced increase of p-AMPK.

    Voir tous les produits spécifiques à Isoform AMPK:

    Voir toutes les isoformes
    NUAK1 NUAK2 AMPK AMPK α1β1γ1 AMPK α2β1γ1 AMPK α1β2γ1 AMPK α2β2γ1

    Voir tous les produits spécifiques à Isoform TGF-β Receptor:

    Voir toutes les isoformes
    ALK1 ALK2 ALK3 ALK4 ALK5 ALK6 ALK7 TGFβR2 ACVR2A ACVR2B
    Description

    Dorsomorphin (Compound C) is a selective and ATP-competitive AMPK inhibitor (Ki=109 nM in the absence of AMP). Dorsomorphin (BML-275) selectively inhibits BMP type I receptors ALK2, ALK3, and ALK6. Dorsomorphin can reverse autophagy activation and anti-inflammatory effect of Urolithin A (HY-100599)[1][2].

    IC50 & Target[1][2]

    AMPK

    109 nM (Ki)

    ACVR1

     

    BMPR1A

     

    ALK6

     

    Autophagy

     

    Cellular Effect
    Cell Line Type Value Description References
    A2780 EC50
    0.9 μM
    Compound: 1; Cpd C
    Antimitotic activity against human A2780 cells by ATP lite luminescence assay
    Antimitotic activity against human A2780 cells by ATP lite luminescence assay
    [PMID: 31831383]
    MCF7 EC50
    4.9 μM
    Compound: 1; Cpd C
    Antimitotic activity against human MCF7 cells by ATP lite luminescence assay
    Antimitotic activity against human MCF7 cells by ATP lite luminescence assay
    [PMID: 31831383]
    In Vitro

    Dorsomorphin (compound C) (0-10 μM, 18 h) suppresses 2DG-induced GRP78 promoter activity in human fibrosarcoma HT1080 cells in a dose-dependent manner but has little effect on tunicamycin-induced GRP78 promoter activity. Dorsomorphin (compound C) C also suppresses GRP78 promoter activity induced by glucose withdrawal. Dorsomorphin (compound C) has no effect on 2DG-induced PERK activation and reduces the both basal and 2DG-induced AMPK phosphorylation levels in HT1080 cells[2].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Western Blot Analysis[2]

    Cell Line: Human fibrosarcoma HT1080 cells
    Concentration: 0-10 μM.
    Incubation Time: 18 hours.
    Result: Suppressed 2DG-induced GRP78 promoter activity in a dose-dependent manner and also suppressed GRP78 promoter activity induced by glucose withdrawal.
    In Vivo

    Dorsomorphin (compound C: 10 mg/kg, intravenously once) treatment leads to a 60% increase in total serum iron concentrations, reduces basal levels of hepcidin expression and increasing serum iron concentrations in adult mice[3].
    Dorsomorphin (compound C: 0.2 mg/kg, I.V., 30 min before LPS injection) reduces ICAM-1 and VCAM-1 expression in LPS-injected rat aorta[4].
    Dorsomorphin (compound C; 25 mg/kg; i.p. injection; in male BALB/c mice) treatment before lipopolysaccharide (LPS) injection significantly reduces lethality in contrast to animals treated with LPS challenge only[5].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    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.
    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.
    Masse moléculaire

    399.49

    Formule

    C24H25N5O

    CAS No.

    866405-64-3

    Appearance

    Solid

    Color

    Light yellow to yellow

    SMILES

    C12=C(C3=CC=NC=C3)C=NN1C=C(C4=CC=C(OCCN5CCCCC5)C=C4)C=N2

    Livraison

    Room temperature in continental US; may vary elsewhere.

    Stockage

    4°C, protect from light

    *In solvent : -80°C, 2 years; -20°C, 1 year (protect from light)

    Solvant et solubilité
    In Vitro: 

    1M HCl : 50 mg/mL (125.16 mM; ultrasonic and adjust pH to 1 with HCl)

    DMSO : 25 mg/mL (62.58 mM; ultrasonic and adjust pH to 3 with 1 M HCL; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    H2O : < 0.1 mg/mL (insoluble)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.5032 mL 12.5160 mL 25.0319 mL
    5 mM 0.5006 mL 2.5032 mL 5.0064 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (protect from light). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Calculateur de molarité

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    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

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    In Vivo:

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  50% PEG300    50% Saline

      Solubility: 10 mg/mL (25.03 mM); Suspended solution; Need ultrasonic and warming and heat to 35°C

    • Protocol 2

      Add each solvent one by one:  0.5% CMC/saline water

      Solubility: 10 mg/mL (25.03 mM); Suspended solution; Need ultrasonic

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

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    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Calculation results:
    Working solution concentration: mg/mL
    Pureté et documentation

    Purity: 99.91%

    Références
    • [1]. Zhou G, et al. Role of AMP-activated protein kinase in mechanism of action. J Clin Invest. 2001 Oct;108(8):1167-74.  [Content Brief]

      [2]. Kim YM, et al. Compound C independent of AMPK inhibits ICAM-1 and VCAM-1 expression in inflammatory stimulants-activated endothelial cells in vitro and in vivo. Atherosclerosis. 2011 Nov;219(1):57-64.  [Content Brief]

      [3]. Saito S, et al. Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling. PLoS One. 2012;7(9):e45845.  [Content Brief]

      [4]. Guo Y, et al. AMPK inhibition blocks ROS-NFκB signaling and attenuates endotoxemia-induced liver injury. PLoS One. 2014 Jan 24;9(1):e86881.  [Content Brief]

      [5]. Yu PB, et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 2008 Jan;4(1):33-41.  [Content Brief]

      [6]. Zhang Y, et al. Urolithin A suppresses glucolipotoxicity-induced ER stress and TXNIP/NLRP3/IL-1β inflammation signal in pancreatic β cells by regulating AMPK and autophagy. Phytomedicine. 2021 Dec;93:153741.  [Content Brief]

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (protect from light). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO / 1M HCl 1 mM 2.5032 mL 12.5160 mL 25.0319 mL 62.5798 mL
    5 mM 0.5006 mL 2.5032 mL 5.0064 mL 12.5160 mL
    10 mM 0.2503 mL 1.2516 mL 2.5032 mL 6.2580 mL
    15 mM 0.1669 mL 0.8344 mL 1.6688 mL 4.1720 mL
    20 mM 0.1252 mL 0.6258 mL 1.2516 mL 3.1290 mL
    25 mM 0.1001 mL 0.5006 mL 1.0013 mL 2.5032 mL
    30 mM 0.0834 mL 0.4172 mL 0.8344 mL 2.0860 mL
    40 mM 0.0626 mL 0.3129 mL 0.6258 mL 1.5645 mL
    50 mM 0.0501 mL 0.2503 mL 0.5006 mL 1.2516 mL
    60 mM 0.0417 mL 0.2086 mL 0.4172 mL 1.0430 mL
    1M HCl 80 mM 0.0313 mL 0.1564 mL 0.3129 mL 0.7822 mL
    100 mM 0.0250 mL 0.1252 mL 0.2503 mL 0.6258 mL
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    Dorsomorphin Related Classifications

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    Keywords:

    Dorsomorphin866405-64-3Compound C BML-275BML275BML 275BML-275OrganoidAMPKTGF-β ReceptorAutophagyAMP-activated protein kinaseTransforming growth factor beta receptorsATP-competitiveBMPtypeIreceptorsInhibitorinhibitorinhibit

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