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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PKCiota-IN-2

PKCiota-IN-2 is a potent PKCiota (PKC-ι) inhibitor with an IC50 of 2.8 nM. PKCiota-IN-2 also inhibits PKC-α and PKC-ε with IC50s of 71 nM and 350 nM, respectively[1].

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

PKCη pseudosubstrate inhibitor,myristoylated

PKCη pseudosubstrate inhibitor,myristoylated is cell permeable and can be used to study the mechanism of action of PKCη[1].

  • CAS Number: 908012-19-1
  • MF: C101H185N41O23S
  • MW: 2373.88
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MY-673

MY-673 is a colchicine binding site inhibitor (CBSI), that inhibits tubulin polymerization. MY-673 inhibits the ERK signaling pathway, which in turn affects SMAD4 protein expression levels in the TGF-β/SMAD pathway. MY-673 inhibited cell proliferation, migration and induced apoptosis in vivo and in vitro[1].

  • CAS Number: 2944459-96-3
  • MF: C18H14N2O4
  • MW: 322.31
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ALK5-IN-28

ALK5-IN-28 (compound Ex-05) is a selective ALK-5 inhibitor (IC50≤10 nM), inhibits TGF-β-induced SMAD signaling. ALK5-IN-28 has the potential to inhibit growth of tumour in vivo. ALK5-IN-28 can be used in study of proliferative diseases such as cancer, fibrotic diseases, and systemic sclerosis[1].

  • CAS Number: 2785430-84-2
  • MF: C25H27N7
  • MW: 425.53
  • Catalog: TGF-beta/Smad
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CC-90005

CC-90005 is a potent, selective and orally active inhibitor of protein kinase C-θ (PKC-θ), with an IC50 of 8 nM. CC-90005 shows selectivity for PKC-θ over PKC-δ (IC50=4440 nM). CC-90005 can inhibit T cell activation by IL-2 expression[1].

  • CAS Number: 1799574-70-1
  • MF: C21H27F2N7O2
  • MW: 447.48
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Phorbol-12

Phorbol 12,13-dibutyrate (Phorbol dibutyrate) is a PKC activator and a potent skin tumor promoter[1][2].

  • CAS Number: 37558-16-0
  • MF: C28H40O8
  • MW: 504.61200
  • Catalog: PKC
  • Density: 1.27g/cm3
  • Boiling Point: 623.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 199.3ºC

LY2109761

LY2109761 is an orally active, selective TGF-β receptor type I/II inhibitor with Kis of 38 nM and 300 nM, respectively.

  • CAS Number: 700874-71-1
  • MF: C26H27N5O2
  • MW: 441.525
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 640.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 341.4±31.5 °C

anemonin

(Rac)-Anemonin ((Rac)-Pulsatilla camphor) is the diastereoisomer of Anemonin (HY-N0278). 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: 90921-11-2
  • MF: C10H8O4
  • MW: 192.17
  • Catalog: PKC
  • Density: 1.45±0.1 g/cm3 (20 ºC 760 Torr)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Livmoniplimab

Livmoniplimab (ABBV-151; ARGX-115) is a potent humanized anti-LRRC32 (GARP)/TGFβ1 monoclonal antibody. Livmoniplimab blocks LRRC32-mediated activation of latent TGFβ1. Livmoniplimab has the potential for the research of cancer[1].

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

(S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine

(S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine is a dual target PROTAC that can not only target to the ubiquitination and degradation of Smad3 but also improve the HIF-α protein level. (S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine has a multi-path anti-fibrosis function and a renal protection function for research of renal anemia[1].

  • CAS Number: 2347517-69-3
  • MF: C41H46N6O6S
  • MW: 750.91
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TGFβ-IN-2

TGFβ-IN-2 (Compound 9d) inhibits TGF-β-induced total collagen accumulation in NRK-49F cells with the IC50 of 4.31 μM. TGFβ-IN-2 suppresses the TGF-β-induced protein expression of COL1A1, α-SMA, and p-Smad3 in vitro. TGFβ-IN-2 can be used as a potential effective compound for anti-fibrosis in vivo by oral administration[1].

  • CAS Number: 2387678-02-4
  • MF: C22H22N2O4
  • MW: 378.42
  • Catalog: TGF-beta/Smad
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-Leu-Ser-Lys-Leu-NH2 trifluoroacetate salt

LSKL, Inhibitor of Thrombospondin (TSP-1) is a peptide derived from the latency-associated peptide, inhibits thrombospondin (TSP-1) activation of TGF-β and prevents the progression of hepatic damage and fibrosis.

  • CAS Number: 283609-79-0
  • MF: C21H42N6O5
  • MW: 458.595
  • Catalog: Peptides
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 817.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 448.4±34.3 °C

Galunisertib (LY2157299)

Galunisertib (LY2157299) is a selective TGF-β receptor inhibitor with an IC50 of 56 nM.

  • CAS Number: 700874-72-2
  • MF: C22H19N5O
  • MW: 369.419
  • Catalog: TGF-β Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 619.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 328.2±31.5 °C

PKCβII Peptide Inhibitor I

PKCβII Peptide Inhibitor I is a PKCβII inhibitor. PKCβII Peptide Inhibitor I shows cardioprotective effects in rat cardiac Ischemia/reperfusion injury model. PKCβII Peptide Inhibitor I also prevents vascular endothelial dysfunction[1].

  • CAS Number: 862502-26-9
  • MF: C61H94N12O19
  • MW: 1299.47000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rock-in-d2

ROCK-IN-D2 is an effective and selective inhibitor of ROCK.

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

Rho Kinase Inhibitor III,Rockout

3-(4-Pyridyl)indole (Rockout) is a Rho-kinase (ROCK) inhibitor, with an IC50 of 25 μM. 3-(4-Pyridyl)indole can inhibit blebbing and cause dissolution of actin stress fibers in a wound healing assay[1].

  • CAS Number: 7272-84-6
  • MF: C13H10N2
  • MW: 194.23200
  • Catalog: ROCK
  • Density: 1.211g/cm3
  • Boiling Point: 406.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 185.2ºC

Phosphate acceptor peptide

Phosphate acceptor peptide is a substrate for cAMP-dependent protein kinase (PKA). phosphate acceptor peptide is also a weak PKC inhibitor[1].

  • CAS Number: 93511-94-5
  • MF: C41H74N16O11
  • MW: 967.13
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AR-13503

AR-13503 a ROCK/PKC inhibitor, inhibiting angiogenesis and enhancing retinal pigment epithelium (RPE) permeability. AR-13503 also inhibits the formation of aberrant neovascularization (NV) in oxygen-induced retinopathy (OIR) model in mice[1][2].

  • CAS Number: 1254032-16-0
  • MF: C19H19N3O2
  • MW: 321.37
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H7

PKC-IN-5 (compound H-7) is a potent PKC (protein kinase C) inhibitor. At 100 μM, PKC-IN-5 completely inhibits both TPA (skin tumour promoter, 12-O-tetradecanoylphorbol-13-acetate) and phospholipase C-induced ODC (ornithine decarboxylase)[1].

  • CAS Number: 108930-17-2
  • MF: C14H19Cl2N3O2S
  • MW: 364.291
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: 495.3ºC at 760mmHg
  • Melting Point: 215-225 °C
  • Flash Point: 253.3ºC

LDN-193189 HCl

LDN193189 Hydrochloride is a BMP signaling inhibitor, inhibiting ALK1, ALK2, ALK3 and ALK6 with IC50s of 0.8, 0.8, 5.3, 16.7 nM, respectively.

  • CAS Number: 1062368-62-0
  • MF: C25H26Cl4N6
  • MW: 552.33
  • Catalog: TGF-β Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ruboxistaurin-d6 hydrochloride

Ruboxistaurin-d6 (LY333531-d6) hydrochloride is the deuterium labeled Ruboxistaurin hydrochloride. Ruboxistaurin (LY333531) hydrochloride is an orally active, selective PKC beta inhibitor (Ki=2 nM). Ruboxistaurin hydrochloride exhibits ATP dependent competitive inhibition of PKC beta I with an IC50 of 4.7 nM. Ruboxistaurin hydrochloride inhibits PKC beta II with an IC50 of 5.9 nM[1][2].

  • CAS Number: 1794767-04-6
  • MF: C28H23D6ClN4O3
  • MW: 511.04
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SAR-407899

SAR407899 is a selective, potent and ATP-competitive ROCK inhibitor, with an IC50 of 135 nM for ROCK-2, and Kis of 36 nM and 41 nM for human and rat ROCK-2, respectively.

  • CAS Number: 923359-38-0
  • MF: C14H16N2O2
  • MW: 244.289
  • Catalog: ROCK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 517.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 267.0±30.1 °C

Ruboxistaurin mesylate

Ruboxistaurin (LY333531) mesylate is an orally active, selective and ATP competitive PKCβ inhibitor with IC50 values of 4.7 and 5.9 nM for PKCβI and PKCβII, respectively. Ruboxistaurin mesylate can be used for the research of eye disorders, heart failure and diabetes[1][2][3][4].

  • CAS Number: 192050-59-2
  • MF: C29H32N4O6S
  • MW: 564.65300
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKCβ inhibitor 1

PKCβ inhibitor 1 is a potent, ATP-competitive, and selective PKCβ inhibitor with IC50s of 21 and 5 nM for human PKCβ1 and PKCβ2, respectively. PKCβ inhibitor 1 exhibits selectivity of more than 60-fold in favor of PKCβ2 relative to other PKC isozymes (PKCα, PKCγ, and PKCε)[1][2].

  • CAS Number: 257879-35-9
  • MF: C24H21N5O2
  • MW: 411.45600
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKCδ Peptide Substrate

PKCδ Peptide Substrate is an absolutely specific substrate for the δ-type of PKC, with a sequence corresponding to sequence 422-443 of murine eEF-1α and containing Thr-431[1].

  • CAS Number: 813416-46-5
  • MF: C109H191N35O29S
  • MW: 2487.97
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mongersen

Mongersen is a 21-mer phosphorothioate antisense oligonucleotide targeting the mRNA of the Smad7 protein, thus leading to suppression of TGF-β1 pathways and remission of Crohn's disease.

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

K-115

Ripasudil (K-115) is a specific inhibitor of ROCK, with IC50s of 19 and 51 nM for ROCK2 and ROCK1, respectively.

  • CAS Number: 887375-67-9
  • MF: C15H23ClFN3O4S
  • MW: 395.877
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bryostatin 1

Bryostatin 1 is a natural macrolide isolated from the bryozoan Bugula neritina and is a potent and central nervous system (CNS)-permeable PKC modulator. Bryostatin 1 binds to the isolated C1 domain of Munc13-1 and the full-length Munc13-1 protein with Kis of 8.07 nM and 0.45 nM, respectively. Bryostatin 1 has anti-cancer, anti-inflammatory, neuroprotective, anti-HIV-1 infection properties[1][2][3][4].

  • CAS Number: 83314-01-6
  • MF: C47H68O17
  • MW: 905.033
  • Catalog: HIV
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 954.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 270.0±27.8 °C

Carotuximab

Carotuximab (TRC105) is a IgG1 monoclonal antibody that blocks endoglin (CD105) and its downstream Smad signaling pathway. Carotuximab has immunomodulatory and antineoplastic actions[1][2].

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

Rock-in-32

ROCK-IN-32 is an effective Rho-kinase inhibitor.

  • CAS Number: 1013117-40-2
  • MF: C20H17Cl2N3O2
  • MW: 402.28
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A