TGF-beta/Smad

TGF-beta/Smad製品

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  • TGF-beta/Smad阻害剤 (36)
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S1067 SB431542 SB431542 は強力かつ選択的 ALK5 阻害剤であり、cell-free assay における IC50 は 94 nM です。p38 MAPK などのキナーゼよりも ALK5 に対して 100 倍の選択性を有しています。
Nature, 2024, 10.1038/s41586-024-07067-y
Nat Methods, 2024, 10.1038/s41592-024-02172-2
Nat Commun, 2024, 15(1):1351
S7306 Dorsomorphin 2HCl Dorsomorphin 2HCl is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type Ⅰ BMP receptor activity. Dorsomorphin induces autophagy in cancer cell line.
Adv Sci (Weinh), 2024, 11(4):e2304987
Genome Biol, 2024, 25(1):58
Cell Death Discov, 2024, 10(1):95
S7840 Dorsomorphin Dorsomorphin is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy. For animal testing, the water-soluble S7306 Dorsomorphin (Compound C) 2HCl is recommended.
Clin Immunol, 2024, 261:109940
iScience, 2024, 27(2):108852
J Ethnopharmacol, 2024, 324:117814
S2618 LDN-193189 LDN-193189 (DM3189) is a selective BMP signaling inhibitor, inhibits the ALK1, ALK2, ALK3 and ALK6 with IC50s of 0.8 nM, 0.8 nM, 5.3 nM and 16.7 nM in the kinase assay, respectively. LDN-193189 inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50s of 5 nM and 30 nM in C2C12 cells, respectively, exhibits 200-fold selectivity for BMP versus TGF-β. For animal testing, the water-soluble S7507 LDN-193189 2HCl is recommended.This product has poor solubility, animal experiments are available, cell experiments please choose carefully!
Nat Cell Biol, 2024, 26(3):353-365
Cells, 2024, 13(3)285
Regen Ther, 2024, 25:229-237
S2230 Galunisertib (LY2157299) Galunisertib (LY2157299) is a potent TGFβ receptor I (TβRI) inhibitor with IC50 of 56 nM in a cell-free assay. Phase 2/3.
Nat Commun, 2023, 14(1):3593
Cell Rep, 2023, 42(7):112804
Oncogene, 2023, 42(22):1857-1873
S2704 LY2109761 LY2109761 is a novel selective TGF-β receptor type I/II (TβRI/II) dual inhibitor with Ki of 38 nM and 300 nM in a cell-free assay, respectively; shown to negatively affect the phosphorylation of Smad2. LY2109761 blocks autophagy and induces apoptosis.
Int J Mol Sci, 2024, 25(2)959
Mol Cancer, 2023, 22(1):66
Cells, 2023, 12(12)1624
S1476 SB525334 SB525334 is a potent and selective inhibitor of TGFβ receptor I (ALK5) with IC50 of 14.3 nM in a cell-free assay, 4-fold less potent to ALK4 than ALK5 and inactive to ALK2, 3, and 6.
Cancer Res, 2023, 83(18):3095-3114
Cell Rep, 2023, 42(3):112162
Br J Cancer, 2023, none
S7507 LDN-193189 2HCl LDN-193189 (DM3189) 2HCl is a selective BMP signaling inhibitor, inhibits the ALK1, ALK2, ALK3 and ALK6 with IC50s of 0.8 nM, 0.8 nM, 5.3 nM and 16.7 nM in the kinase assay, respectively. LDN-193189 inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50s of 5 nM and 30 nM in C2C12 cells, respectively, exhibits 200-fold selectivity for BMP versus TGF-β.
Cell Res, 2023, 10.1038/s41422-023-00846-8
Stem Cell Res Ther, 2023, 14(1):378
Front Cell Dev Biol, 2023, 11:1236243
S7959 SIS3 HCl SIS3, a novel specific inhibitor of Smad3, inhibits TGF-β and activin signaling by suppressing Smad3 phosphorylation without affecting the MAPK/p38, ERK, or PI3-kinase signaling pathways.
Int J Biol Sci, 2024, 20(1):200-217
J Endocrinol Invest, 2024, 10.1007/s40618-023-02267-1
Nat Commun, 2023, 14(1):1794
S7223 RepSox (E-616452) RepSox (E-616452, SJN 2511, ALK5 Inhibitor II) is a potent and selective inhibitor of the TGFβR-1/ALK5 with IC50 of 23 nM and 4 nM for ATP binding to ALK5 and ALK5 autophosphorylation in cell-free assays, respectively.
Biomolecules, 2024, 14(1)95
Neuron, 2023, 111(9):1381-1390.e6
Cancer Sci, 2023, 10.1111/cas.15987
S2805 LY364947 LY364947 (HTS 466284) is a potent ATP-competitive inhibitor of TGFβR-I with IC50 of 59 nM in a cell-free assay, shows 7-fold selectivity over TGFβR-II.
Adv Sci (Weinh), 2024, 11(4):e2304987
Cell Rep Med, 2024, 5(2):101416
Cell Rep, 2023, 42(6):112566
S2907 Pirfenidone Pirfenidone is an inhibitor for TGF-β production and TGF-β stimulated collagen production, reduces production of TNF-α and IL-1β, and also has anti-fibrotic and anti-inflammatory properties. Pirfenidone attenuates chemokine (CC motif) ligand-2 (CCL2) and CCL12 production with anti-fibrotic activity. Phase 3.
Eur Respir J, 2024, 2300580
Cells, 2024, 13(2)164
Acta Pharmacol Sin, 2023, 10.1038/s41401-023-01156-w
S7146 DMH1 DMH1 is a selective BMP receptor inhibitor with IC50 of 107.9 nM for ALK2, exhibiting no inhibition on AMPK, ALK5, KDR (VEGFR-2) or PDGFR. DMH1 inhibits autophagy.
J Exp Med, 2024, 221(5)e20221190
Neural Regen Res, 2024, 19(1):205-211
iScience, 2024, 27(3):109166
S2186 SB505124 SB505124 is a selective inhibitor of TGFβR for ALK4, ALK5 with IC50 of 129 nM and 47 nM in cell-free assays, respectively, also inhibits ALK7, but does not inhibit ALK1, 2, 3, or 6.
Nat Commun, 2023, 14(1):4417
Nat Commun, 2023, 14(1):143
Nat Commun, 2023, 14(1):4417
S2750 GW788388 GW788388 is a potent and selective inhibitor of ALK5 with IC50 of 18 nM in a cell-free assay, also inhibits TGF-β type II receptor and activin type II receptor activities, but does not inhibit BMP type II receptor.
Mol Carcinog, 2024, 10.1002/mc.23715
J Biol Chem, 2023, 299(4):103017
Cell Rep, 2022, 40(13):111423
S7692 A-83-01 A-83-01 is a potent inhibitor of TGF-β type I receptor (ALK5-TD) with IC50 of 12 nM. A-83-01 also inhibits the transcription induced by activin/nodal type I receptor (ALK4-TD) and nodal type I receptor (ALK7-TD) with IC50 of 45 nM and 7.5 nM, respectively.Solutions are unstable and should be fresh-prepared.
Nat Commun, 2024, 15(1):668
Nat Commun, 2024, 15(1):583
Stem Cell Reports, 2024, 19(2):196-210
S7359 K02288 K02288 is a potent, and selective type I BMP receptor inhibitor with IC50 of 1.1, 1.8, 6.4 nM for ALK2, ALK1 and ALK6, showing weaker inhibition on other ALKs (3, 4, 5) and ActRIIA.
FEBS J, 2024, 291(2):272-291
J Neurooncol, 2024, 10.1007/s11060-024-04625-2
Int J Mol Sci, 2022, 23(3)1475
S7624 SD-208 SD-208 is a selective TGF-βRI (ALK5) inhibitor with IC50 of 48 nM, >100-fold selectivity over TGF-βRII.
JCI Insight, 2023, 8(3)e166688
Cancers (Basel), 2023, 10.3390/cancers15205086
Cancers (Basel), 2023, 15(20)5086
S7530 Vactosertib (TEW-7197) Vactosertib  (TEW-7197, EW-7197) is a highly potent, selective, and orally bioavailable TGF-β receptor ALK4/ALK5 inhibitor with IC50 of 13 nM and 11 nM, respectively. Phase 1.
bioRxiv, 2023, 10.1101/2023.12.14.571626
Res Sq, 2023, rs.3.rs-3112163
Acta Pharmacol Sin, 2022, 10.1038/s41401-022-00932-4
S1576 Sulfasalazine Sulfasalazine is a sulfa derivative of mesalazine, used as an anti-inflammatory agent to treat bowel disease and rheumatoid arthritis. Sulfasalazine is a potent and specific inhibitor of nuclear factor kappa B (NF-κB), TGF-β and COX-2. Sulfasalazine induces ferroptosis, apoptosis and autophagy.
Adv Sci (Weinh), 2023, 10(20):e2300517
Proc Natl Acad Sci U S A, 2022, 119(36):e2117396119
Cell Mol Life Sci, 2022, 79(5):228
S3552 SIS3 SIS3 is a cell-permeable inhibitor of Smad3 that selectively inhibits TGF-β1-dependent Smad3 phosphorylation and Smad3-mediated cellular signaling. SIS3 reduces TGF-β1-induced type 1 procollagen expression and myofibroblast differentiation in normal dermal fibroblasts as well as scleroderma fibroblasts.
Front Bioeng Biotechnol, 2023, 11:1281157
Front Bioeng Biotechnol, 2023, 11:1281157
J Dent Sci, 2023, 18(1):87-94
S7658 Kartogenin Kartogenin (KGN) is an activator of the smad4/smad5 pathway, and promotes the selective differentiation of multipotent mesenchymal stem cells into chondrocytes.
Pharmaceutics, 2023, 15(7)1949
Int J Mol Sci, 2022, 24(1)390
Front Pharmacol, 2022, 13:922032
S6713 ITD-1 ITD-1 is a potent TGF-β inhibitor. It does not block the kinase activity of either type I (TGFBR1) or type II (TGFBR2) TGFβ receptors but potently blocks phosphorylation of the effector SMAD2/3 proteins induced by TGFβ2, and only minimally in response to Activin A.
Front Pharmacol, 2024, 15:1257941
Cell Mol Biol Lett, 2023, 28(1):32
J Cell Commun Signal, 2023, 10.1007/s12079-023-00766-7
S8144 Halofuginone Halofuginone (RU-19110) is the competitively inhibitor of prolyl-tRNA synthetase with Ki of 18.3 nM.It could also down-regulate Smad3 and blocked TGF-β signaling at 10 ng/ml in mammal.
Infect Agent Cancer, 2023, 18(1):27
FASEB J, 2022, 36(11):e22580
Invest Ophthalmol Vis Sci, 2022, 63(8):1
S7147 LDN-212854 LDN-212854 (BMP Inhibitor III) is a potent and selective BMP receptor inhibitor with IC50 of 1.3 nM for ALK2, about 2-, 66-, 1641-, and 7135-fold selectivity over ALK1, ALK3, ALK4, and ALK5, respectively.
Am J Pathol, 2023, S0002-9440(23)00047-0
Am J Pathol, 2023, 193(5):532-547
Int J Mol Sci, 2022, 23(3)1475
S8772 LY 3200882 LY 3200882 is a potent, highly selective inhibitor of TGF-β receptor type 1 (TGFβRI). It potently inhibits TGFβ mediated SMAD phosphorylation in vitro in tumor and immune cells and in vivo in subcutaneous tumors in a dose dependent fashion.
J Inflamm Res, 2021, 14:2897-2911
Pediatr Rheumatol Online J, 2021, 19(1):72
Br J Cancer, 2020, 10.1038/s41416-020-01040-y
S7148 ML347 ML347 (LDN-193719) is a selective BMP receptor inhibitor with IC50 of 32 nM for ALK2, >300-fold selectivity over ALK3. Also inhibits ALK1 activity with IC50 of 46 nM.
Development, 2022, 149(20)dev192310
Biomolecules, 2020, 10(4)E519
Biomolecules, 2020, 29;10(4) pii: E519
S8700 TP0427736 HCl TP0427736 is a potent inhibitor of ALK5 kinase activity with an IC50 of 2.72 nM and this effect is 300-fold higher than the inhibitory effect on ALK3 (IC50 = 836 nM for ALK3). It also inhibits Smad2/3 phosphorylation in A549 cells induced by TGF-β1 with an IC50 value of 8.68 nM.
Commun Biol, 2023, 6(1):824
Nutrients, 2023, 16(1)64
Int J Mol Sci, 2023, 24(19)14444
S6654 SRI-011381 (C381) SRI-011381 (C381) is a novel agonist of the TGF-beta signaling pathway for treatment of Alzheimer's disease.C381 physically targets the lysosome, promotes lysosomal acidification, increases breakdown of lysosomal cargo, and improves lysosome resilience to damage.
Dis Model Mech, 2022, dmm.046979
Front Cell Dev Biol, 2021, 9:648201
Eur J Pharmacol, 2021, 912:174587
S7627 LDN-214117 LDN-214117 is a potent and selective BMP type I receptor kinase ALK2 inhibitor with IC50 of 24 nM.
bioRxiv, 2023, 2023.06.14.544941
FASEB J, 2021, 35(3):e21263
Stem Cells Int, 2019, 2019:5026793
S2308 Hesperetin Hesperetin is a bioflavonoid and, to be more specific, a flavanone.
J Transl Med, 2024, 22(1):208
Sci Rep, 2022, 12(1):7
Front Pharmacol, 2021, 12:735087
S7914 Isoxazole 9 (ISX-9) Isoxazole 9 (Isx-9) is a synthetic promotor of adult neurogenesis by triggering neuronal differentiation of adult neural stem/precursor cells (NSPCs). Isoxazole 9 (Isx-9) activates multiple pathways including TGF-β induced epithelial–mesenchymal transition (EMT) signaling, canonical and non-canonical Wnt signaling at different stages of cardiac differentiation.
Commun Biol, 2022, 5(1):750
Front Cell Dev Biol, 2021, 9:728352
Front Cell Dev Biol, 2021, 9:728352
S8318 Alantolactone Alantolactone, a naturally occurring eudesmane-type sesquiterpene lactone (SL), could induce activin/SMAD3 signaling and disrupt Cripto-1/activin receptor type II A interaction.
Nat Commun, 2022, 13(1):107
Onco Targets Ther, 2017, 10:1767-1776
E2394 TGFβRI-IN-3 TGFβRI-IN-3 represents a highly selective TGFβR1 inhibitor that has potential applications in immuno-oncology, inhibits TGFβR1 at an IC50 of 0.79 nM with 2000-fold selectivity against MAP4K4.
JCI Insight, 2023, e161563
S5183 PD 169316 PD 169316 is a potent, selective and cell-permeable p38 MAP kinase inhibitor with IC50 of 89 nM. PD169316 abrogates signaling initiated by both TGFbeta and Activin A. PD169316 shows antiviral activity against Enterovirus71.
PLoS One, 2021, 16(5):e0252541
S3223 L-Quebrachitol L-Quebrachitol (L-QCT), a natural product isolated from many plants, promotes proliferation and cell DNA synthesis. L-Quebrachitol upregulates bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor-2 (Runx2) and regulatory genes associated with mitogen-activated protein kinase (MAPK) and Wnt/β-catenin signaling pathway, while down-regulating the receptor activator of the nuclear factor-κB(NF-κB) ligand (RANKL) mRNA level.
E4432New 3,3-Dimethyl-1-butanol 3,3-Dimethyl-1-butanol (Neohexanol) is an orally active inhibitor of trimethylamine (TMA) and trimethylamine N-oxide (TMAO). 3,3-dimethyl-1-butanol negatively inhibits the signalling pathways of p65 NF-κB and  TGF-β1/Smad3. 3,3-dimethyl-1-butanol has potential applications in cardiovascular disease (CVD).
S0523 SB 4 SB 4 is a potent and selective agonist of bone morphogenetic protein 4 (BMP4) signaling with EC50 of 74 nM. SB 4 enhances canonical BMP signaling and activates SMAD-1/5/9 phosphorylation.
S0752 AUDA AUDA (compound 43) is a potent inhibitor of soluble epoxide hydrolase (sEH) with IC50 of 18 nM and 69 nM for the mouse sEH and human sEH, respectively. AUDA has anti-inflammatory activity that reduces the protein expression of MMP-9, IL-1β, TNF-α and TGF-β. AUDA downregulates Smad3 and p38 signaling pathways.
S2234 BIBF-0775 BIBF-0775 is a selective inhibitor of transforming growth factor β Receptor I (TGFβRI,Alk5) with an IC50 of 34 nM.
E0769 Ginsenoside Rh4 Ginsenoside Rh4 is an important active ingredient of traditional Chinese medicine ginseng, which has been shown to inhibit Wnt/β-Catenin, JAK2/STAT3, TGF-β/Smad2/3 and other signaling pathways.
S0153 SJ000291942 SJ000291942 is a canonical bone morphogenetic proteins (BMP) signaling pathway activator.
S7710 R-268712 R-268712 is a potent and selective inhibitor of ALK5 with an IC50 of 2.5 nM.
S6807 TA-02 TA-02 is a p38 MAPK inhibitor with IC50 of 20 nM. TA-02 especially inhibits TGFBR-2.
S6654 SRI-011381 (C381) SRI-011381 (C381) is a novel agonist of the TGF-beta signaling pathway for treatment of Alzheimer's disease.C381 physically targets the lysosome, promotes lysosomal acidification, increases breakdown of lysosomal cargo, and improves lysosome resilience to damage.
Dis Model Mech, 2022, dmm.046979
Front Cell Dev Biol, 2021, 9:648201
Eur J Pharmacol, 2021, 912:174587
S0523 SB 4 SB 4 is a potent and selective agonist of bone morphogenetic protein 4 (BMP4) signaling with EC50 of 74 nM. SB 4 enhances canonical BMP signaling and activates SMAD-1/5/9 phosphorylation.
S1067 SB431542 SB431542 は強力かつ選択的 ALK5 阻害剤であり、cell-free assay における IC50 は 94 nM です。p38 MAPK などのキナーゼよりも ALK5 に対して 100 倍の選択性を有しています。
Nature, 2024, 10.1038/s41586-024-07067-y
Nat Methods, 2024, 10.1038/s41592-024-02172-2
Nat Commun, 2024, 15(1):1351
S7306 Dorsomorphin 2HCl Dorsomorphin 2HCl is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type Ⅰ BMP receptor activity. Dorsomorphin induces autophagy in cancer cell line.
Adv Sci (Weinh), 2024, 11(4):e2304987
Genome Biol, 2024, 25(1):58
Cell Death Discov, 2024, 10(1):95
S7840 Dorsomorphin Dorsomorphin is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy. For animal testing, the water-soluble S7306 Dorsomorphin (Compound C) 2HCl is recommended.
Clin Immunol, 2024, 261:109940
iScience, 2024, 27(2):108852
J Ethnopharmacol, 2024, 324:117814
S2618 LDN-193189 LDN-193189 (DM3189) is a selective BMP signaling inhibitor, inhibits the ALK1, ALK2, ALK3 and ALK6 with IC50s of 0.8 nM, 0.8 nM, 5.3 nM and 16.7 nM in the kinase assay, respectively. LDN-193189 inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50s of 5 nM and 30 nM in C2C12 cells, respectively, exhibits 200-fold selectivity for BMP versus TGF-β. For animal testing, the water-soluble S7507 LDN-193189 2HCl is recommended.This product has poor solubility, animal experiments are available, cell experiments please choose carefully!
Nat Cell Biol, 2024, 26(3):353-365
Cells, 2024, 13(3)285
Regen Ther, 2024, 25:229-237
S2230 Galunisertib (LY2157299) Galunisertib (LY2157299) is a potent TGFβ receptor I (TβRI) inhibitor with IC50 of 56 nM in a cell-free assay. Phase 2/3.
Nat Commun, 2023, 14(1):3593
Cell Rep, 2023, 42(7):112804
Oncogene, 2023, 42(22):1857-1873
S2704 LY2109761 LY2109761 is a novel selective TGF-β receptor type I/II (TβRI/II) dual inhibitor with Ki of 38 nM and 300 nM in a cell-free assay, respectively; shown to negatively affect the phosphorylation of Smad2. LY2109761 blocks autophagy and induces apoptosis.
Int J Mol Sci, 2024, 25(2)959
Mol Cancer, 2023, 22(1):66
Cells, 2023, 12(12)1624
S1476 SB525334 SB525334 is a potent and selective inhibitor of TGFβ receptor I (ALK5) with IC50 of 14.3 nM in a cell-free assay, 4-fold less potent to ALK4 than ALK5 and inactive to ALK2, 3, and 6.
Cancer Res, 2023, 83(18):3095-3114
Cell Rep, 2023, 42(3):112162
Br J Cancer, 2023, none
S7507 LDN-193189 2HCl LDN-193189 (DM3189) 2HCl is a selective BMP signaling inhibitor, inhibits the ALK1, ALK2, ALK3 and ALK6 with IC50s of 0.8 nM, 0.8 nM, 5.3 nM and 16.7 nM in the kinase assay, respectively. LDN-193189 inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50s of 5 nM and 30 nM in C2C12 cells, respectively, exhibits 200-fold selectivity for BMP versus TGF-β.
Cell Res, 2023, 10.1038/s41422-023-00846-8
Stem Cell Res Ther, 2023, 14(1):378
Front Cell Dev Biol, 2023, 11:1236243
S7959 SIS3 HCl SIS3, a novel specific inhibitor of Smad3, inhibits TGF-β and activin signaling by suppressing Smad3 phosphorylation without affecting the MAPK/p38, ERK, or PI3-kinase signaling pathways.
Int J Biol Sci, 2024, 20(1):200-217
J Endocrinol Invest, 2024, 10.1007/s40618-023-02267-1
Nat Commun, 2023, 14(1):1794
S7223 RepSox (E-616452) RepSox (E-616452, SJN 2511, ALK5 Inhibitor II) is a potent and selective inhibitor of the TGFβR-1/ALK5 with IC50 of 23 nM and 4 nM for ATP binding to ALK5 and ALK5 autophosphorylation in cell-free assays, respectively.
Biomolecules, 2024, 14(1)95
Neuron, 2023, 111(9):1381-1390.e6
Cancer Sci, 2023, 10.1111/cas.15987
S2805 LY364947 LY364947 (HTS 466284) is a potent ATP-competitive inhibitor of TGFβR-I with IC50 of 59 nM in a cell-free assay, shows 7-fold selectivity over TGFβR-II.
Adv Sci (Weinh), 2024, 11(4):e2304987
Cell Rep Med, 2024, 5(2):101416
Cell Rep, 2023, 42(6):112566
S2907 Pirfenidone Pirfenidone is an inhibitor for TGF-β production and TGF-β stimulated collagen production, reduces production of TNF-α and IL-1β, and also has anti-fibrotic and anti-inflammatory properties. Pirfenidone attenuates chemokine (CC motif) ligand-2 (CCL2) and CCL12 production with anti-fibrotic activity. Phase 3.
Eur Respir J, 2024, 2300580
Cells, 2024, 13(2)164
Acta Pharmacol Sin, 2023, 10.1038/s41401-023-01156-w
S7146 DMH1 DMH1 is a selective BMP receptor inhibitor with IC50 of 107.9 nM for ALK2, exhibiting no inhibition on AMPK, ALK5, KDR (VEGFR-2) or PDGFR. DMH1 inhibits autophagy.
J Exp Med, 2024, 221(5)e20221190
Neural Regen Res, 2024, 19(1):205-211
iScience, 2024, 27(3):109166
S2186 SB505124 SB505124 is a selective inhibitor of TGFβR for ALK4, ALK5 with IC50 of 129 nM and 47 nM in cell-free assays, respectively, also inhibits ALK7, but does not inhibit ALK1, 2, 3, or 6.
Nat Commun, 2023, 14(1):4417
Nat Commun, 2023, 14(1):143
Nat Commun, 2023, 14(1):4417
S2750 GW788388 GW788388 is a potent and selective inhibitor of ALK5 with IC50 of 18 nM in a cell-free assay, also inhibits TGF-β type II receptor and activin type II receptor activities, but does not inhibit BMP type II receptor.
Mol Carcinog, 2024, 10.1002/mc.23715
J Biol Chem, 2023, 299(4):103017
Cell Rep, 2022, 40(13):111423
S7692 A-83-01 A-83-01 is a potent inhibitor of TGF-β type I receptor (ALK5-TD) with IC50 of 12 nM. A-83-01 also inhibits the transcription induced by activin/nodal type I receptor (ALK4-TD) and nodal type I receptor (ALK7-TD) with IC50 of 45 nM and 7.5 nM, respectively.Solutions are unstable and should be fresh-prepared.
Nat Commun, 2024, 15(1):668
Nat Commun, 2024, 15(1):583
Stem Cell Reports, 2024, 19(2):196-210
S7359 K02288 K02288 is a potent, and selective type I BMP receptor inhibitor with IC50 of 1.1, 1.8, 6.4 nM for ALK2, ALK1 and ALK6, showing weaker inhibition on other ALKs (3, 4, 5) and ActRIIA.
FEBS J, 2024, 291(2):272-291
J Neurooncol, 2024, 10.1007/s11060-024-04625-2
Int J Mol Sci, 2022, 23(3)1475
S7624 SD-208 SD-208 is a selective TGF-βRI (ALK5) inhibitor with IC50 of 48 nM, >100-fold selectivity over TGF-βRII.
JCI Insight, 2023, 8(3)e166688
Cancers (Basel), 2023, 10.3390/cancers15205086
Cancers (Basel), 2023, 15(20)5086
S7530 Vactosertib (TEW-7197) Vactosertib  (TEW-7197, EW-7197) is a highly potent, selective, and orally bioavailable TGF-β receptor ALK4/ALK5 inhibitor with IC50 of 13 nM and 11 nM, respectively. Phase 1.
bioRxiv, 2023, 10.1101/2023.12.14.571626
Res Sq, 2023, rs.3.rs-3112163
Acta Pharmacol Sin, 2022, 10.1038/s41401-022-00932-4
S1576 Sulfasalazine Sulfasalazine is a sulfa derivative of mesalazine, used as an anti-inflammatory agent to treat bowel disease and rheumatoid arthritis. Sulfasalazine is a potent and specific inhibitor of nuclear factor kappa B (NF-κB), TGF-β and COX-2. Sulfasalazine induces ferroptosis, apoptosis and autophagy.
Adv Sci (Weinh), 2023, 10(20):e2300517
Proc Natl Acad Sci U S A, 2022, 119(36):e2117396119
Cell Mol Life Sci, 2022, 79(5):228
S3552 SIS3 SIS3 is a cell-permeable inhibitor of Smad3 that selectively inhibits TGF-β1-dependent Smad3 phosphorylation and Smad3-mediated cellular signaling. SIS3 reduces TGF-β1-induced type 1 procollagen expression and myofibroblast differentiation in normal dermal fibroblasts as well as scleroderma fibroblasts.
Front Bioeng Biotechnol, 2023, 11:1281157
Front Bioeng Biotechnol, 2023, 11:1281157
J Dent Sci, 2023, 18(1):87-94
S6713 ITD-1 ITD-1 is a potent TGF-β inhibitor. It does not block the kinase activity of either type I (TGFBR1) or type II (TGFBR2) TGFβ receptors but potently blocks phosphorylation of the effector SMAD2/3 proteins induced by TGFβ2, and only minimally in response to Activin A.
Front Pharmacol, 2024, 15:1257941
Cell Mol Biol Lett, 2023, 28(1):32
J Cell Commun Signal, 2023, 10.1007/s12079-023-00766-7
S8144 Halofuginone Halofuginone (RU-19110) is the competitively inhibitor of prolyl-tRNA synthetase with Ki of 18.3 nM.It could also down-regulate Smad3 and blocked TGF-β signaling at 10 ng/ml in mammal.
Infect Agent Cancer, 2023, 18(1):27
FASEB J, 2022, 36(11):e22580
Invest Ophthalmol Vis Sci, 2022, 63(8):1
S7147 LDN-212854 LDN-212854 (BMP Inhibitor III) is a potent and selective BMP receptor inhibitor with IC50 of 1.3 nM for ALK2, about 2-, 66-, 1641-, and 7135-fold selectivity over ALK1, ALK3, ALK4, and ALK5, respectively.
Am J Pathol, 2023, S0002-9440(23)00047-0
Am J Pathol, 2023, 193(5):532-547
Int J Mol Sci, 2022, 23(3)1475
S8772 LY 3200882 LY 3200882 is a potent, highly selective inhibitor of TGF-β receptor type 1 (TGFβRI). It potently inhibits TGFβ mediated SMAD phosphorylation in vitro in tumor and immune cells and in vivo in subcutaneous tumors in a dose dependent fashion.
J Inflamm Res, 2021, 14:2897-2911
Pediatr Rheumatol Online J, 2021, 19(1):72
Br J Cancer, 2020, 10.1038/s41416-020-01040-y
S7148 ML347 ML347 (LDN-193719) is a selective BMP receptor inhibitor with IC50 of 32 nM for ALK2, >300-fold selectivity over ALK3. Also inhibits ALK1 activity with IC50 of 46 nM.
Development, 2022, 149(20)dev192310
Biomolecules, 2020, 10(4)E519
Biomolecules, 2020, 29;10(4) pii: E519
S8700 TP0427736 HCl TP0427736 is a potent inhibitor of ALK5 kinase activity with an IC50 of 2.72 nM and this effect is 300-fold higher than the inhibitory effect on ALK3 (IC50 = 836 nM for ALK3). It also inhibits Smad2/3 phosphorylation in A549 cells induced by TGF-β1 with an IC50 value of 8.68 nM.
Commun Biol, 2023, 6(1):824
Nutrients, 2023, 16(1)64
Int J Mol Sci, 2023, 24(19)14444
S7627 LDN-214117 LDN-214117 is a potent and selective BMP type I receptor kinase ALK2 inhibitor with IC50 of 24 nM.
bioRxiv, 2023, 2023.06.14.544941
FASEB J, 2021, 35(3):e21263
Stem Cells Int, 2019, 2019:5026793
E2394 TGFβRI-IN-3 TGFβRI-IN-3 represents a highly selective TGFβR1 inhibitor that has potential applications in immuno-oncology, inhibits TGFβR1 at an IC50 of 0.79 nM with 2000-fold selectivity against MAP4K4.
JCI Insight, 2023, e161563
S5183 PD 169316 PD 169316 is a potent, selective and cell-permeable p38 MAP kinase inhibitor with IC50 of 89 nM. PD169316 abrogates signaling initiated by both TGFbeta and Activin A. PD169316 shows antiviral activity against Enterovirus71.
PLoS One, 2021, 16(5):e0252541
E4432New 3,3-Dimethyl-1-butanol 3,3-Dimethyl-1-butanol (Neohexanol) is an orally active inhibitor of trimethylamine (TMA) and trimethylamine N-oxide (TMAO). 3,3-dimethyl-1-butanol negatively inhibits the signalling pathways of p65 NF-κB and  TGF-β1/Smad3. 3,3-dimethyl-1-butanol has potential applications in cardiovascular disease (CVD).
S0752 AUDA AUDA (compound 43) is a potent inhibitor of soluble epoxide hydrolase (sEH) with IC50 of 18 nM and 69 nM for the mouse sEH and human sEH, respectively. AUDA has anti-inflammatory activity that reduces the protein expression of MMP-9, IL-1β, TNF-α and TGF-β. AUDA downregulates Smad3 and p38 signaling pathways.
S2234 BIBF-0775 BIBF-0775 is a selective inhibitor of transforming growth factor β Receptor I (TGFβRI,Alk5) with an IC50 of 34 nM.
E0769 Ginsenoside Rh4 Ginsenoside Rh4 is an important active ingredient of traditional Chinese medicine ginseng, which has been shown to inhibit Wnt/β-Catenin, JAK2/STAT3, TGF-β/Smad2/3 and other signaling pathways.
S7710 R-268712 R-268712 is a potent and selective inhibitor of ALK5 with an IC50 of 2.5 nM.
S6807 TA-02 TA-02 is a p38 MAPK inhibitor with IC50 of 20 nM. TA-02 especially inhibits TGFBR-2.
S7658 Kartogenin Kartogenin (KGN) is an activator of the smad4/smad5 pathway, and promotes the selective differentiation of multipotent mesenchymal stem cells into chondrocytes.
Pharmaceutics, 2023, 15(7)1949
Int J Mol Sci, 2022, 24(1)390
Front Pharmacol, 2022, 13:922032
S7914 Isoxazole 9 (ISX-9) Isoxazole 9 (Isx-9) is a synthetic promotor of adult neurogenesis by triggering neuronal differentiation of adult neural stem/precursor cells (NSPCs). Isoxazole 9 (Isx-9) activates multiple pathways including TGF-β induced epithelial–mesenchymal transition (EMT) signaling, canonical and non-canonical Wnt signaling at different stages of cardiac differentiation.
Commun Biol, 2022, 5(1):750
Front Cell Dev Biol, 2021, 9:728352
Front Cell Dev Biol, 2021, 9:728352
S3223 L-Quebrachitol L-Quebrachitol (L-QCT), a natural product isolated from many plants, promotes proliferation and cell DNA synthesis. L-Quebrachitol upregulates bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor-2 (Runx2) and regulatory genes associated with mitogen-activated protein kinase (MAPK) and Wnt/β-catenin signaling pathway, while down-regulating the receptor activator of the nuclear factor-κB(NF-κB) ligand (RANKL) mRNA level.
S0153 SJ000291942 SJ000291942 is a canonical bone morphogenetic proteins (BMP) signaling pathway activator.
S6654 SRI-011381 (C381) SRI-011381 (C381) is a novel agonist of the TGF-beta signaling pathway for treatment of Alzheimer's disease.C381 physically targets the lysosome, promotes lysosomal acidification, increases breakdown of lysosomal cargo, and improves lysosome resilience to damage.
Dis Model Mech, 2022, dmm.046979
Front Cell Dev Biol, 2021, 9:648201
Eur J Pharmacol, 2021, 912:174587
S0523 SB 4 SB 4 is a potent and selective agonist of bone morphogenetic protein 4 (BMP4) signaling with EC50 of 74 nM. SB 4 enhances canonical BMP signaling and activates SMAD-1/5/9 phosphorylation.
S2308 Hesperetin Hesperetin is a bioflavonoid and, to be more specific, a flavanone.
J Transl Med, 2024, 22(1):208
Sci Rep, 2022, 12(1):7
Front Pharmacol, 2021, 12:735087
S8318 Alantolactone Alantolactone, a naturally occurring eudesmane-type sesquiterpene lactone (SL), could induce activin/SMAD3 signaling and disrupt Cripto-1/activin receptor type II A interaction.
Nat Commun, 2022, 13(1):107
Onco Targets Ther, 2017, 10:1767-1776
E4432New 3,3-Dimethyl-1-butanol 3,3-Dimethyl-1-butanol (Neohexanol) is an orally active inhibitor of trimethylamine (TMA) and trimethylamine N-oxide (TMAO). 3,3-dimethyl-1-butanol negatively inhibits the signalling pathways of p65 NF-κB and  TGF-β1/Smad3. 3,3-dimethyl-1-butanol has potential applications in cardiovascular disease (CVD).

TGF-beta/Smad阻害剤の選択性比較

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