The TGF-β superfamily comprises TGF-βs, bone morphogenetic proteins (BMPs), activins and related proteins. These proteins were identified mainly through their roles in development; they regulate the establishment of the body plan and tissue differentiation through their effects on cell proliferation, differentiation and migration. There are eight vertebrate Smads: Smad1 to Smad8. Smad2 and Smad3 are activated through carboxy-terminal phosphorylation by the TGF-b and activin receptors TbRI and ActRIB, whereas Smad1, Smad5 and Smad8 are activated by ALK-1, ALK-2, BMP-RIA/ALK-3 and BMP-RIB/ALK-6 in response to BMP1–4 or other ligands.

TGF-β binds two receptor types, the TGF-β type I and type II receptors (TβRI and TβRII, respectively) to form the active signaling complex. The TβRII activates TβRI kinase activity by phosphorylating the TβRI, which then transmits the signal intracellularly by phosphorylating the Smad transcription factors. The Smads constitutively shuttle between the cytoplasm and nucleus, but signaling causes the Smads to accumulate predominantly in the nucleus where they bind DNA and other transcriptional machinery to regulate the expression of target genes. TGF-β also involves in the regulations of PI3K and MAPK signaling pathways.

Abnormalities of the TGF-beta receptors and SMADs have been detected in various tumors, including colorectal cancers and pancreatic cancers. In addition, TGF-β/BMP signaling is also involved in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption ofTGF-β/BMP signaling.

References:
[1] Derynck R, et al. Nature. 2003 Oct 9;425(6958):577-84.
[2] Clarke DC, et al. Trends Cell Biol. 2008 Sep;18(9):430-42.
[3] Wu M, et al. Bone Res. 2016 Apr 26;4:16009.


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(S)-Ro 32-0432 free base

(S)-Ro 32-0432 free base is a potent, selective, ATP-competitive and orally active PKC inhibitor. The IC50 values of (S)-Ro 32-0432 free base for PKCα, PKCβI, PKCβII, PKCγ and PKCε are 9.3 nM, 28 nM, 30 nM, 36.5 nM and 108.3 nM, respectively. (S)-Ro 32-0432 free base is also a selective G protein-coupled receptor kinase 5 (GRK5) inhibitor. (S)-Ro 32-0432 free base prevents T-cell activation and has the potential for chronic inflammatory and autoimmune diseases research[1][2].

  • CAS Number: 151342-35-7
  • MF: C28H28N4O2
  • MW: 452.55
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: 711.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 384.3ºC

Bisindolylmaleimide I HCl

Bisindolylmaleimide I (GF109203X) hydrochloride is a cell-permeable and reversible PKC inhibitor (IC50 of 20 nM, 17 nM, 16 nM, and 20 nM for PKCα, PKCβI, PKCβII, and PKCγ. Bisindolylmaleimide I hydrochloride is also a GSK-3 inhibitor[1][2][3].

  • CAS Number: 176504-36-2
  • MF: C25H25ClN4O2
  • MW: 448.94500
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CCG-232964

CCG-232964 is an orally active inhibitor of Rho/MRTF/SRF. CCG-232964 inhibits LPA-induced CTGF gene expression[1].

  • CAS Number: 2349373-70-0
  • MF: C15H15ClN2O3S
  • MW: 338.81
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Belumosudil mesylate

Belumosudil mesylate (KD025 mesylate) is a selective inhibitor of ROCK2 with IC50s of 105 nM and 24 µM for ROCK2 and ROCK1, respectively. Anti-fibrotic properties[1].

  • CAS Number: 2109704-99-4
  • MF: C27H28N6O5S
  • MW: 548.61
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Ser25)-Protein Kinase C (19-31)

[Ser25] Protein Kinase C (19-31) is a substrate of protein kinase C (PKC) (Km: 0.3 μM). [Ser25] Protein Kinase C (19-31) is derived from the pseudo-substrate regulatory domain of PKCα (19-31) with a Serine at position 25 replacing the wild-type Alanine[1].

  • CAS Number: 136795-05-6
  • MF: C67H118N26O17
  • MW: 1559.818
  • Catalog: PKC
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB505124

SB-505124 is a selective inhibitor of TGFβR with IC50 of 129 nM and 47 nM for ALK4, ALK5, respectively, and it does not inhibits ALK1, 2, 3, or 6 but ALK7.

  • CAS Number: 694433-59-5
  • MF: C20H21N3O2
  • MW: 335.400
  • Catalog: TGF-β Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 509.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 180.5±20.4 °C

Kartogenin

Kartogenin is an inducer of differentiation of human mesenchymal stem cells into chondrocytes.

  • CAS Number: 4727-31-5
  • MF: C20H15NO3
  • MW: 317.338
  • Catalog: TGF-beta/Smad
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 464.4±38.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 234.6±26.8 °C

Ro 32-0432 hydrochloride

Ro 32-0432 hydrochloride is a potent, selective, ATP-competitive and orally active PKC inhibitor. The IC50 values of Ro 32-0432 hydrochloride for PKCα, PKCβI, PKCβII, PKCγ and PKCε are 9.3 nM, 28 nM, 30 nM, 36.5 nM and 108.3 nM, respectively. Ro 32-0432 hydrochloride is also a selective G protein-coupled receptor kinase 5 (GRK5) inhibitor. Ro 32-0432 hydrochloride prevents T-cell activation and has the potential for chronic inflammatory and autoimmune diseases research[1][2].

  • CAS Number: 1781828-85-0
  • MF: C28H29ClN4O2
  • MW: 489.01
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pirfenidone

Pirfenidone is a drug used for the treatment of idiopathic pulmonary fibrosis. It inhibits FGFR, EGFR, PDGFR, TGF-β, thereby slowing tumor cell proliferation.

  • CAS Number: 53179-13-8
  • MF: C12H11NO
  • MW: 185.222
  • Catalog: TGF-beta/Smad
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 329.1±15.0 °C at 760 mmHg
  • Melting Point: 96-97ºC
  • Flash Point: 152.7±11.6 °C

K 02288

K02288 is a potent inhibitor of ALK, and inhibits ALK1/2/3/6 with IC50s of 1.8/1.1/34.4/6.3 nM; K02288 is less potent against ALK4/5, with IC50s of 302 nM and 321 nM.

  • CAS Number: 1431985-92-0
  • MF: C20H20N2O4
  • MW: 352.384
  • Catalog: ALK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 522.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 269.6±30.1 °C

D,L-erythro-Dihydrosphingosine

DL-erythro-Dihydrosphingosine is a potent inhibitor of PKC and phospholipase A2 (PLA2)[1][2].

  • CAS Number: 3102-56-5
  • MF: C18H39NO2
  • MW: 301.50800
  • Catalog: PKC
  • Density: 0.927g/cm3
  • Boiling Point: 446.2ºC at 760 mmHg
  • Melting Point: 70-72ºC
  • Flash Point: 223.7ºC

Go 6983

Go 6983 is a pan-PKC inhibitor against for PKCα, PKCβ, PKCγ, PKCδ and PKCζ with IC50 of 7 nM, 7 nM, 6 nM, 10 nM and 60 nM, respectively.

  • CAS Number: 133053-19-7
  • MF: C26H26N4O3
  • MW: 442.510
  • Catalog: PKC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 709.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.6±32.9 °C

1-amino-8-naphthol-2,4-disulfonic acid monosodium salt

CaMKP inhibitor sodium is a selective inhibitor of ROCK1 with an IC50 value of 14 nM.

  • CAS Number: 52789-62-5
  • MF: C10H8NNaO7S2
  • MW: 341.29
  • Catalog: ROCK
  • Density: 1.477 g/mL at 25 °C(lit.)
  • Boiling Point: 270-272 °C(lit.)
  • Melting Point: 12-16 °C(lit.)
  • Flash Point: >230 °F

SB525334

SB 525334 is a potent and selective transforming growth factor β1 receptor (ALK5) inhibitor with an IC50 of 14.3 nM.

  • CAS Number: 356559-20-1
  • MF: C21H21N5
  • MW: 343.425
  • Catalog: TGF-β Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 540.5±45.0 °C at 760 mmHg
  • Melting Point: 159 °C
  • Flash Point: 238.6±21.7 °C

CGP60474

CGP60474 is a potent VEGFR-2 inhibitor, with an IC50 of 84 nM, and also an ATP-competitive PKC inhibitor.

  • CAS Number: 164658-13-3
  • MF: C18H18ClN5O
  • MW: 355.82100
  • Catalog: PKC
  • Density: 1.356g/cm3
  • Boiling Point: 630.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 335.2ºC

Elezanumab

Elezanumab (ABT-555; AE12-1Y-QL) is a human monoclonal antibody that selectively targets repulsive guidance molecule A (RGMa). Elezanumab potently inhibited RGMa mediated BMP signalling via the SMAD1/5/8 pathway, with an IC50 around 97 pM. Elezanumab promotes neuroregeneration and neuroprotection in neuronal injury and demyelination models binds N-terminal RGMa, blocks BMP signaling and lacks RGMc cross-reactivity. elezanumab has neuroregenerative and neuroprotective activities without impact on iron metabolism[1][2].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ROCK-IN-8

ROCK-IN-8 (Example 4) is a ROCK inhibitor, with an IC50 value less than 100 nM. ROCK-IN-8 has anti-inflammatory activity. ROCK-IN-8 can be used for research of respiratory and gastro-intestinal diseases[1].

  • CAS Number: 1621103-79-4
  • MF: C30H25FN4O4S
  • MW: 556.61
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

K252C

K-252c, a staurosporine analog isolated from Nocardiopsis sp., is a cell-permeable PKC inhibitor, with an IC50 of 2.45 µM. K-252c induces apoptosis in human chronic myelogenous leukemia cancer cells. K-252c also inhibits β-lactamase, chymotrypsin, and malate dehydrogenase[1][2][3].

  • CAS Number: 85753-43-1
  • MF: C20H13N3O
  • MW: 311.33700
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Staurosporine

Staurosporine is a potent and non-selective inhibitor of protein kinases with IC50s of 6 nM, 15 nM, 2 nM, and 3 nM for PKC, PKA, c-Fgr, and Phosphorylase kinase respectively.

  • CAS Number: 62996-74-1
  • MF: C28H26N4O3
  • MW: 466.531
  • Catalog: PKC
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 677.5±55.0 °C at 760 mmHg
  • Melting Point: 270ºC
  • Flash Point: 363.6±31.5 °C

6,7,4'-Trihydroxyisoflavone

Desmethylglycitein (4',6,7-Trihydroxyisoflavone), a metabolite of daidzein, sourced from Glycine max with antioxidant, and anti-cancer activities.Desmethylglycitein binds directly to CDK1 and CDK2 in vivo, resulting in the suppresses CDK1 and CDK2 activity[1]. Desmethylglycitein is a direct inhibitor of protein kinase C (PKC)α, against solar UV (sUV)-induced matrix matrix metalloproteinase 1 (MMP1)[2]. Desmethylglycitein binds to PI3K in an ATP competitive manner in the cytosol, where it inhibits the activity of PI3K and downstream signaling cascades, leading to the suppression of adipogenesis in 3T3-L1 preadipocytes[3].

  • CAS Number: 17817-31-1
  • MF: C15H10O5
  • MW: 270.23700
  • Catalog: CDK
  • Density: 1.548g/cm3
  • Boiling Point: 587.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 229.7ºC

Epsilon-V1-2

Epsilon-V1-2 (ε-V1-2), a PKCε-derived peptide, is a selective PKCε inhibitor. Epsilon-V1-2 inhibits the translocationof PKCε, but not α-, β-, and δPKC[1].

  • CAS Number: 182683-50-7
  • MF: C37H65N9O13
  • MW: 843.964
  • Catalog: PKC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1280.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 728.0±34.3 °C

Anemonine

Anemonin (Pulsatilla camphor), a selective iNOS inhibitor, is also a PKC-θ inhibitor. Anemonin can significantly inhibit the translation or protein stability of PKC-θ protein. Anemonin also ameliorates dextran sodium sulfate-induced acute ulcerative colitis (UC) in mice. Anemonin can be used in the research of inflammation-related diseases[1][2].

  • CAS Number: 508-44-1
  • MF: C10H8O4
  • MW: 192.17
  • Catalog: PKC
  • Density: 1.45
  • Boiling Point: 535.7ºC at 760 mmHg
  • Melting Point: 157-158ºC
  • Flash Point: 300.7ºC

H-Arg-Gly-Tyr-Ala-Leu-Gly-OH

H-Arg-Gly-Tyr-Ala-Leu-Gly-OH is a competitive and CAMP dependent protein kinase inhibitor[1].

  • CAS Number: 59587-24-5
  • MF: C28H45N9O8
  • MW: 635.71200
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

oxymatrine

Oxymatrine, an alkaloid from the roots of Sophora species, with anti-inflammatory, antifibrosis, and antitumor effects, inhibits the iNOS expression and TGF-β/Smad pathway.

  • CAS Number: 16837-52-8
  • MF: C15H24N2O2
  • MW: 264.363
  • Catalog: TGF-beta/Smad
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chebulinic acid

Chebulinic acid is a potent natural inhibitor of M. tuberculosis DNA gyrase, also can inhibit SMAD-3 phosphorylation, inhibit H+ K+-ATPase activity.

  • CAS Number: 18942-26-2
  • MF: C41H32O27
  • MW: 956.677
  • Catalog: DNA/RNA Synthesis
  • Density: 2.0±0.1 g/cm3
  • Boiling Point: 1460.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 437.2±27.8 °C

A-3 hydrochloride

A-3 hydrochloride is a potent, cell-permeable, reversible, ATP-competitive non-selective antagonist of various kinases. It against PKA (Ki=4.3 µM), casein kinase II (Ki=5.1 µM) and myosin light chain kinase (MLCK) (Ki=7.4 µM). A-3 hydrochloride also inhibits PKC and casein kinase I with Ki values of 47 µM and 80 µM, respectively[1].

  • CAS Number: 78957-85-4
  • MF: C12H14Cl2N2O2S
  • MW: 321.22300
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 173-176ºC
  • Flash Point: N/A

ala-gly-asn-lys-val-ile-ser-pro-ser-glu-asp-arg-arg-gln-cys

Protein kinase C (alpha) peptide (TFA) is a peptide of PKC-α. PKC-α acts as a lipid-dependent ser/thr protein kinase, can modulate various cellular processes, including cell survival, proliferation, differentiation, migration, adhesion and so on[1].

  • CAS Number: 159939-84-1
  • MF: C66H114N24O24S
  • MW: 1659.82000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SY-LB-35

SY-LB-35 is a potent bone morphogenetic protein (BMP) receptor agonist. SY-LB-35 can stimulate significant increases in cell number and cell viability in the C2C12 myoblast cell line, and causes shifts towards the S and G2/M phases of the cell cycle. SY-LB-35 stimulates canonical Smad and non-canonical PI3K/Akt, ERK, p38 and JNK intracellular signaling pathways[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Go6976

Go6976 is a Protein Kinase C (PKC) inhibitor, with an IC50 of 20 nM.

  • CAS Number: 136194-77-9
  • MF: C24H18N4O
  • MW: 378.426
  • Catalog: PKC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 652.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 348.3±31.5 °C

SB431542

SB-431542 is a potent and selective inhibitor of ALK5 with an IC50 value of 94 nM, and is also an inhibitor of TGF-β Receptor.

  • CAS Number: 301836-41-9
  • MF: C22H16N4O3
  • MW: 384.387
  • Catalog: TGF-β Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 662.4±55.0 °C at 760 mmHg
  • Melting Point: 214 °C(dec.)
  • Flash Point: 354.4±31.5 °C