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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Myristoyl-Lys-Arg-Thr-Leu-Arg-OH

N-Myristoyl-Lys-Arg-Thr-Leu-Arg is a protein kinase C (PKC) inhibitor with an IC50 value of 75 μM. N-Myristoyl-Lys-Arg-Thr-Leu-Arg inhibits IL-2 receptor induction and IL-2 production in the human leukemic cell line Jurkat[1].

  • CAS Number: 125678-68-4
  • MF: C42H82N12O8
  • MW: 883.17600
  • Catalog: PKC
  • Density: 1.26g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ingenol 3,20-dibenzoate

Ingenol 3,20-dibenzoate is a potent protein kinase C (PKC) isoform-selective agonist. Ingenol 3,20-dibenzoate induces selective translocation of nPKC-delta, -epsilon, and -theta and PKC-mu from the cytosolic fraction to the particulate fraction and induces morphologically typical apoptosis through de novo synthesis of macromolecules. Ingenol 3,20-dibenzoate increases the IFN-γ production and degranulation by NK cells, especially when NK cells are stimulated by NSCLC cells[1][2].

  • CAS Number: 59086-90-7
  • MF: C34H36O7
  • MW: 556.64500
  • Catalog: PKC
  • Density: 1.32 g/cm3
  • Boiling Point: 697ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 221.6ºC

Bryostatin 3

Bryostatin 3, a macrocyclic lactone, is a protein kinase C activator, with a Ki of 2.75 nM. Bryostatin 3 can block 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibition of cell proliferation, yet did not block TPA-enhanced cell-substratum adhesion[1][2].

  • CAS Number: 143370-84-7
  • MF: C46H64O17
  • MW: 888.99
  • Catalog: PKC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 993.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 286.2±27.8 °C

Rottlerin

Rottlerin is a specific PKC inhibitor, with IC50 values for PKCδ of 3-6 μM, PKCα,β,γ of 30-42 μM, PKCε,η,ζ of 80-100 μM.

  • CAS Number: 82-08-6
  • MF: C30H28O8
  • MW: 516.539
  • Catalog: PKC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 800.4±65.0 °C at 760 mmHg
  • Melting Point: 200 °C
  • Flash Point: 266.0±27.8 °C

DCPLA-ME

DCPLA-ME, the methyl ester form of DCPLA, is a potent PKCε activator for use in the treatment of neurodegenerative diseases[1].

  • CAS Number: 56687-67-3
  • MF: C21H38O2
  • MW: 322.52500
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KT5823

KT5823, a selective the cGMP-dependent protein kinase (PKG) inhibitor with an Ki value of 0.23 μM, it also inhibits PKA and PKC with Ki values of 10 μM and 4 μM, respectively[1]. KT5823 is a staurosporine-related protein kinase inhibitor, increases thyroid-stimulating hormone-induced (Na+/I- symporter) NIS expression, and iodide uptake in thyroid cells[2]. KT5823 arrests cells after the G0/G1 boundary and causes increases in the levels of apoptotic DNA fragmentation[3].

  • CAS Number: 126643-37-6
  • MF: C29H25N3O5
  • MW: 495.52600
  • Catalog: Apoptosis
  • Density: 1.52g/cm3
  • Boiling Point: 629.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 334.3ºC

ALK5-IN-32

ALK5-IN-32 (compound EX-09) is a selective ALK-5 inhibitor (10 nM

  • CAS Number: 2785430-88-6
  • MF: C23H23FN8
  • MW: 430.48
  • Catalog: TGF-beta/Smad
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-oxo Staurosporine

7-Oxostaurosporine is a potent protein kinase C (PKC) inhibitor that effectively inhibits tumor growth by inducing apoptosis and inhibiting the nuclear factor (NF)-κB/p-p65 pathway[1][2].

  • CAS Number: 125035-83-8
  • MF: C28H24N4O4
  • MW: 480.51500
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PLSRTLSVAAKK

[Ala9,10, Lys11,12] Glycogen Synthase (1-12) is a selective substrate for phosphorylation by protein kinase C (PKC). [Ala9,10, Lys11,12] Glycogen Synthase (1-12) can be used to determine the activity of protein kinase C[1].

  • CAS Number: 105802-84-4
  • MF: C56H103N17O16
  • MW: 1270.52000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ζ-Stat trisodium

ζ-Stat trisodium (NSC37044 trisodium) is a specific and atypical PKC-ζ inhibitor, with an IC50 of 5 μM. ζ-Stat trisodium can reduce melanoma cell lines proliferation and induce apoptosis, and has antitumor activity in vitro[1][2].

  • CAS Number: 31894-34-5
  • MF: C10H5Na3O10S3
  • MW: 450.31
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thiazovivin

Thiazovivin is a potent ROCK inhibitor, which can protect human embryonic stem cells.

  • CAS Number: 1226056-71-8
  • MF: C15H13N5OS
  • MW: 311.362
  • Catalog: ROCK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKC Substrate 2

Protein kinase C substrate is a substrate of Protein kinase C, can be used to detect protein. Protein kinase C is a key regulatory element in signal transduction and exerts its effects by catalysing specific substrate phosphorylation[1].

  • CAS Number: 105802-82-2
  • MF: C51H100N22O11
  • MW: 1197.48000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rhodblock 6

Rhodblock 6 is a Rho kinase (ROCK) inhibitor that inhibits phospho-MRLC (myosin regulatory light chain) localization[1].

  • CAS Number: 886625-06-5
  • MF: C12H13N3O
  • MW: 215.25
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CAY10746

CAY10746 is a selective Rho kinase (ROCK) inhibitor. CAY10746 has inhibitory activity for ROCK I, ROCK II with IC50 values of 0.014 μM and 0.003 μM, respectively. CAY10746 can be used for the research of diabetic retinopathy (DR)[1].

  • CAS Number: 2247240-76-0
  • MF: C26H23N3O5
  • MW: 457.478
  • Catalog: ROCK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 664.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 355.5±31.5 °C

CMPD101

CMPD101, is a novel membrane-permeable, small-molecule inhibitor of both GRK2 and GRK3 with IC50s of 18 nM and 5.4 nM. CMPD101 also inhibits ROCK-2 and PKCα (IC50s=1.4 μM and 8.1 μM, respectively)[1].

  • CAS Number: 865608-11-3
  • MF: C24H21F3N6O
  • MW: 466.458
  • Catalog: ROCK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PS315

PS315, a derivative of PS48 (HY-15967), is an allosteric PKC inhibitor by binding to the PIF-pocket of aPKC and inducing a displacement of the active site residue Lys111. PS315 inhibits the full-length and catalytic domain constructs of PKCζ (IC50=10 μM) and PKCη (IC50=30 μM). PS315 has anti-cancer activity[1].

  • CAS Number: 1221964-50-6
  • MF: C23H19ClO2
  • MW: 362.85
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Narciclasine

Narciclasine is a plant growth modulator. Narciclasine modulates the Rho/Rho kinase/LIM kinase/cofilin signaling pathway, greatly increasing GTPase RhoA activity as well as inducing actin stress fiber formation in a RhoA-dependent manner.

  • CAS Number: 29477-83-6
  • MF: C14H13NO7
  • MW: 307.255
  • Catalog: ROCK
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 733.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 397.6±32.9 °C

BJE6-106

BJE6-106 (B106) is a potent, selective 3rd generation PKCδ inhibitor with an IC50 of 0.05 μM and targets selectivity over classical PKC isozyme PKCα (IC50=50 μM). BJE6-106 (B106) induces caspase-dependent apoptosis. BJE6-106 (B106) possesses tumor-specific effect.

  • CAS Number: 1564249-38-2
  • MF: C26H23NO2
  • MW: 381.47
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hydrochlorothiazid-13C,d2

Hydrochlorothiazid-13C,d2 is the 13C- and deuterium labeled. Hydrochlorothiazide (HCTZ), an orally active diuretic drug of the thiazide class, inhibits transforming TGF-β/Smad signaling pathway. Hydrochlorothiazide has direct vascular relaxant effects via opening of the calcium-activated potassium (KCA) channel. Hydrochlorothiazide improves cardiac function, reduces fibrosis and has antihypertensive effect[1][2][3].

  • CAS Number: 1190006-03-1
  • MF: C613CH6D2ClN3O4S2
  • MW: 300.74
  • Catalog: Potassium Channel
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-[(1R)-1-Aminoethyl]-N-1H-pyrrolo[2,3-b]pyridin-4-ylbenzamide hydrochloride

Y-33075 hydrochloride (Y-39983) is a selective ROCK inhibitor derived from Y-27632, and is more potent than Y-27632, with an IC50 of 3.6 nM.

  • CAS Number: 471843-75-1
  • MF: C16H17ClN4O
  • MW: 316.79
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bisindolylmaleimide X HCl

Bisindolylmaleimide X hydrochloride (BIM-X hydrochloride) is a potent protein kinase C (PKC) inhibitor[1].

  • CAS Number: 145317-11-9
  • MF: C26H25ClN4O2
  • MW: 460.955
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Asiaticoside

Asiaticoside, a trisaccaride triterpene from Centella asiatica, suppresses TGF-β/Smad signaling through inducing Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid fibroblasts; Asiaticoside shows antioxidant, anti-inflammatory, and anti-ulcer properties.

  • CAS Number: 16830-15-2
  • MF: C48H78O19
  • MW: 959.12
  • Catalog: TGF-beta/Smad
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 949.4±65.0 °C at 760 mmHg
  • Melting Point: 235-238ºC
  • Flash Point: 268.4±27.8 °C

Myristoyl-Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu-OH

N-myristoyl-RKRTLRRL inhibits binding of PKC substrates. N-myristoyl-RKRTLRRL inhibits Ca2+- and phosphatidylserine (PS)-dependent histone phosphorylation with IC50 of 5 μM.? histone phosphorylation with IC50 of 80 μM[1][2].

  • CAS Number: 152246-40-7
  • MF: C60H117N21O11
  • MW: 1308.71000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hu7691

Hu7691 is an orally active, selective Akt inhibitor with IC50s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 inhibits tumor growth and enables decrease of cutaneous toxicity in mice[1].

  • CAS Number: 2360523-76-6
  • MF: C22H22ClF3N4O
  • MW: 450.88
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Protein Kinase C (530-558)

Protein Kinase C (530-558), a peptide fragment of protein kinase C (PKC), is a potent PKC activator. Protein Kinase C (530-558) significantly inhibits osteoclastic bone resorption[1].

  • CAS Number: 122613-29-0
  • MF: C148H221N35O50S2
  • MW: 3354.67000
  • Catalog: PKC
  • Density: 1.4±0.1g/cm3
  • Boiling Point: 3001.7±65.0°C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 1769.2±34.3°C

LX7101

LX7101 is a potent inhibitor of LIMK and ROCK2 with IC50 values of 24, 1.6 and 10 nM for LIMK1, LIMK2 and ROCK2, respectively; also inhibits PKA with an IC50 less than 1 nM.

  • CAS Number: 1192189-69-7
  • MF: C23H29N7O3
  • MW: 451.52100
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKCε (85-92)

PKCε (85-92) is a biological active peptide. (This peptide is the e-PKC specific activator, it also activates MARCKS phosphorylation in wild type cells, and has no effect on MARCKS phosphorylation in the cells derived from knockout mice.)

  • CAS Number: 207111-98-6
  • MF: C39H54N10O14
  • MW: 886.90
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OSU-2S

A non-immunosuppressive FTY720 analogue, PKCδ activator with higher antiproliferative potency with IC50 of 2.4, 2.4, and 3.5 uM in Huh7, Hep3B, and PLC5 cells, respectively; exhibited higher in vitro antiproliferative efficacy relative to FTY720 against HCC cells without cytotoxicity in normal hepatocytes, although devoid of S1P1 receptor activity; induces caspase-dependent apoptosis through ROS-dependent PKCδ activation in HCC tumor cells.

  • CAS Number: 1351056-65-9
  • MF: C21H37NO2
  • MW: 335.532
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Enzastaurin (LY317615)

Enzastaurin is a potent and selective PKCβ inhibitor with an IC50 of 6 nM, showing 6- to 20-fold selectivity over PKCα, PKCγ and PKCε.

  • CAS Number: 170364-57-5
  • MF: C32H29N5O2
  • MW: 515.605
  • Catalog: Autophagy
  • Density: 1.34
  • Boiling Point: 767.2±60.0 °C at 760 mmHg
  • Melting Point: 249-261℃
  • Flash Point: 417.8±32.9 °C

1-Deoxysphinganine (m18:0)

Spisulosine (ES-285) is an antiproliferative (antitumoral) compound of marine origin. Spisulosine inhibits the growth of the prostate PC-3 and LNCaP cells through intracellular ceramide accumulation and PKCζ activation[1].

  • CAS Number: 196497-48-0
  • MF: C18H39NO
  • MW: 285.50800
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A