ArticleThe Journal of pharmacology and experimental therapeutics2014
Specific activin receptor-like kinase 3 inhibitors enhance liver regeneration.
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Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Targeting fibroblasts in pathological bone formation: mechanisms and treatments.Frontiers in cell and developmental biology · 2025Review
- Exploring the roles of non-coding RNAs in liver regeneration.Non-coding RNA research · 2024Review
- Review
- Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification.International journal of molecular sciences · 2022Review
- Article
- Targeting heterotopic ossification by inhibiting activin receptor‑like kinase 2 function (Review).Molecular medicine reports · 2019Review
- Bone Morphogenetic Protein-Based Therapeutic Approaches.Cold Spring Harbor perspectives in biology · 2018Review
- Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2.Bone · 2018Review
- TGF-β Family Signaling in Ductal Differentiation and Branching Morphogenesis.Cold Spring Harbor perspectives in biology · 2018Review
- BMP Signalling at the Crossroad of Liver Fibrosis and Regeneration.International journal of molecular sciences · 2017Review
- Liver Regeneration: Analysis of the Main Relevant Signaling Molecules.Mediators of inflammation · 2017Review
- Effect of Secreted Molecules of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells on Acute Hepatic Failure Model.Stem cells and development · 2016Article
- Immunoregulation by members of the TGFβ superfamily.Nature reviews. Immunology · 2016Review
- Bone Morphogenetic Proteins.Cold Spring Harbor perspectives in biology · 2016Review
- BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors.Development (Cambridge, England) · 2016Article
- A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives.Stem cells international · 2016Review
- Activin receptor-like kinases: a diverse family playing an important role in cancer.American journal of cancer research · 2016Review
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Authors and funding
16 authors at 6 institutions in 2 countries.
Daisuke TsugawaThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Yuki OyaThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Ryota MasuzakiThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Kevin RayThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Darren W EngersThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Martin DibThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Nhue DoThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Kaori KuramitsuThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Karen HoThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Audrey FristThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Paul B YuThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Kenneth D BlochThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Craig W LindsleyThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Corey R HopkinsThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Charles C HongThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.).
Seth J KarpThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee (D.T., Y.O., R.M., K.R., S.J.K.); Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Nashville, Tennessee (D.W.E., C.W.L., C.R.H.); Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.D., N.D.); Department of Surgery, Kobe University, Kobe, Japan (K.K.); Department of Surgery (K.H.), and Division of Cardiology, Department of Medicine (P.B.Y.), Brigham and Women's Hospital, Boston, Massachusetts; Anesthesia Center for Critical Care Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts (K.D.B.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (C.W.L.); and Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee (A.F., C.C.H.) seth.karp@vanderbilt.edu.
Vanderbilt University · USMassachusetts General Hospital · USKobe University · JPVanderbilt University Medical Center · USVA Tennessee Valley Healthcare System · USBeth Israel Deaconess Medical Center · US
Funding
Novel probes of BMP and TGF-beta signaling and functionR01AR057374 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI YU, PAUL B · 2010 to 2023
$4.5MCardiac Induction by Small Molecule BMP InhibitorsR01HL104040 · NHLBI · VANDERBILT UNIVERSITY · PI HONG, CHARLES C · 2010 to 2014
$2.0MBMP Signaling--A Therapeutic Target in Liver DiseaseR01DK081387 · NIDDK · VANDERBILT UNIVERSITY · PI KARP, SETH J · 2010 to 2014
$1.7MThe role of the BMP type II receptor in vascular functionK08HL079943 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI YU, PAUL B · 2006 to 2010
$672kNHLBI NIH HHS K08 HL079943NHLBI NIH HHS R01 HL104040NIAMS NIH HHS R01 AR057374NIDDK NIH HHS 7R01-DK081387NIDDK NIH HHS R01 DK081387NIDDK NIH HHS R01-DK0829710
Abstract
Pharmacologic agents to enhance liver regeneration after injury would have wide therapeutic application. Based on previous work suggesting inhibition of bone morphogenetic protein (BMP) signaling stimulates liver regeneration, we tested known and novel BMP inhibitors for their ability to accelerate regeneration in a partial hepatectomy (PH) model. Compounds were produced based on the 3,6-disubstituted pyrazolo[1,5-a] pyrimidine core of the BMP antagonist dorsomorphin and evaluated for their ability to inhibit BMP signaling and enhance liver regeneration. Antagonists of the BMP receptor activin receptor-like kinase 3 (ALK3), including LDN-193189 (LDN; 4-[6-[4-(1-piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-quinoline), DMH2 (4-(2-(4-(3-(quinolin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl)phenoxy)ethyl)morpholine; VU0364849), and the novel compound VU0465350 (7-(4-isopropoxyphenyl)-3-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridine; VU5350), blocked SMAD phosphorylation in vitro and in vivo, and enhanced liver regeneration after PH. In contrast, an antagonist of the BMP receptor ALK2, VU0469381 (5-(6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinolone; 1LWY), did not affect liver regeneration. LDN did not affect liver synthetic or metabolic function. Mechanistically, LDN increased serum interleukin-6 levels and signal transducer and activator of transcription 3 phosphorylation in the liver, and modulated other factors known to be important for liver regeneration, including suppressor of cytokine signaling 3 and p53. These findings suggest that inhibition of ALK3 may be part of a therapeutic strategy for treating human liver disease.
Indexed as
AnimalsBone Morphogenetic Protein Receptors, Type IHumansLiver RegenerationMaleMiceMice, Inbred C57BLProtein Kinase InhibitorsBmpr1a protein, mouseBone Morphogenetic Protein Receptors, Type IProtein Kinase Inhibitors
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