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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Hu7691 free base

Hu7691 free base 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 free base inhibits tumor growth and enables decrease of cutaneous toxicity in mice[1].

  • CAS Number: 2241232-43-7
  • MF: C22H21F3N4O
  • MW: 414.42
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Myristoyl Tetrapeptide-12

Myristoyl tetrapeptide-12 directly activates SMAD2 and induces the linking of SMAD3 with DNA. Myristoyl tetrapeptide-12 is capable of stimulating hair growth, especially at the level of eyelashes[1][2].

  • CAS Number: 959610-24-3
  • MF: C32H63N7O5
  • MW: 625.886
  • Catalog: TGF-beta/Smad
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 932.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 517.6±34.3 °C

R59949

R59949 is a pan diacylglycerol kinase (DGK) inhibitor with an IC50 of 300 nM. R59949 strongly inhibits the activity of type I DGK α and γ and moderately attenuates the activity of type II DGK θ and κ. R59949 activates protein kinase C (PKC) by enhancing the levels of the endogenous ligand diacyl glycerol[1][2][3].

  • CAS Number: 120166-69-0
  • MF: C28H25F2N3OS
  • MW: 489.57900
  • Catalog: PKC
  • Density: 1.36g/cm3
  • Boiling Point: 637.1ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 339.1ºC

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

SRI-011381

SRI-011381 is an orally active TGF-β signaling agonist, exhibits neuroprotective effects[1][2].

  • CAS Number: 1629138-41-5
  • MF: C20H31N3O
  • MW: 329.48
  • Catalog: TGF-beta/Smad
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[Ala107] -MBP(104-118)

[Ala107]MBP(104-118) is an noncompetitive peptide inhibitors of protein kinase C (PKC), with IC50s ranging from 46-145 μM[1].

  • CAS Number: 99026-77-4
  • MF: C67H104N20O19
  • MW: 1493.67000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

K252b

K-252b, an indolocarbazole isolated from the actinomycete Nocardiopsis, is a PKC inhibitor. K-252b can be used to inhibit extracellular kinases of cells in culture because it can’t pass through cell membrane freely [1][2][3].

  • CAS Number: 99570-78-2
  • MF: C26H19N3O5
  • MW: 453.446
  • Catalog: PKC
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 769.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 419.4±32.9 °C

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

Mitoxantrone-d8

Mitoxantrone-d8 (mitozantrone-d8) is the deuterium labeled Mitoxantrone. Mitoxantrone is a topoisomerase II inhibitor and also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM[1][2].

  • CAS Number: 1189974-82-0
  • MF: C22H20D8N4O6
  • MW: 452.53000
  • Catalog: Topoisomerase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 145 °C
  • 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

R 59-022 hydrochloride

R 59-022 (DKGI-I) hydrochloride is a DGK inhibitor (IC50: 2.8 µM). R 59-022 hydrochloride inhibits the phosphorylation of OAG to OAPA. R 59-022 hydrochloride is a 5-HT Receptor antagonist, and activates protein kinase C (PKC). R 59-022 hydrochloride potentiates thrombin-induced diacylglycerol production in platelets and inhibits phosphatidic acid production in neutrophils[1][2][3][4].

  • CAS Number: 93076-98-3
  • MF: C27H27ClFN3OS
  • MW: 496.04
  • 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

Hydrochlorothiazide

Hydrochlorothiazide is a diuretic drug of the thiazide class. Target: OthersHydrochlorothiazide belongs to thiazide class of diuretics. It reduces blood volume by acting on the kidneys to reduce sodium (Na) reabsorption in the distal convoluted tubule. The major site of action in the nephron appears on an electroneutral Na+-Cl? co-transporter by competing for the chloride site on the transporter. By impairing Na transport in the distal convoluted tubule, hydrochlorothiazide induces a natriuresis and concomitant water loss. Thiazides increase the reabsorption of calcium in this segment in a manner unrelated to sodium transport. Additionally, by other mechanisms, Hydrochlorothiazide is believed to lower peripheral vascular resistance [1].

  • CAS Number: 58-93-5
  • MF: C7H8ClN3O4S2
  • MW: 297.739
  • Catalog: TGF-beta/Smad
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 577.0±60.0 °C at 760 mmHg
  • Melting Point: 273 °C
  • Flash Point: 302.7±32.9 °C

ALK5-IN-34

ALK5-IN-34 is an selective orally active activin receptor-like kinase (ALK) inhibitor. ALK5-IN-34 can inhibit the activity of ALK5-IN-34 with an IC50 value of ≤10 nM. ALK5-IN-34 also has inhibitory of tumor growth and can be used for the research of proliferative diseases, such as cancer[1].

  • CAS Number: 2785430-90-0
  • MF: C23H23N7O
  • MW: 413.48
  • Catalog: TGF-beta/Smad
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKC-theta inhibitor

PKC-theta inhibitor is a selective PKC-θinhibitor, with an IC50 of 12 nM.

  • CAS Number: 736048-65-0
  • MF: C20H25F3N6O3
  • MW: 454.45
  • Catalog: PKC
  • 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

3′-O-Demethyl-4′-N-demethyl-4′-N-acetyl-4′-epi-staurosporine

3′-O-Demethyl-4′-N-demethyl-4′-N-acetyl-4′-epi-staurosporine (Compound 7) is an inhibitor of protein kinases, with IC50s of 0.092, 0.26, 0.77 μM for PKC-α, ROCK, ASK1. 3′-O-Demethyl-4′-N-demethyl-4′-N-acetyl-4′-epi-staurosporine shows potent cytotoxicity against PC-3 cancer cells with an IC50 value of 0.16 μM[1].

  • CAS Number: 2226941-29-1
  • MF: C28H24N4O4
  • MW: 480.51
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

pTH-Related Protein (1-40) (human, mouse, rat) trifluoroacetate salt

pTH-Related Protein (1-40) (human, mouse, rat) stimulates calcium uptake in rat intestinal cells through PTHR1 receptor and PKCα/β signaling pathways. pTH-Related Protein (1-40) up-regulates parathyroid hormone 1 receptor (PTHR1) protein, four transcellular calcium transporters, potential vanillin member 6 (TRPV6), calcium-binding protein-D9K (CaBP-D9k), sodium-calcium Exchanger 1 (NCX1) and plasma membrane calcium ATPase 1 (PMCA1)[1].

  • CAS Number: 120298-73-9
  • MF: C207H334N66O58
  • MW:
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zelasudil

Zelasudil is a Rho-associated (ROCK) kinase inhibitor. Zelasudil has a ROCK2 binding affinity[1][2].

  • CAS Number: 2365193-22-0
  • MF: C22H21F2N7O
  • MW: 437.45
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mitoxantrone

Mitoxantrone is a topoisomerase II inhibitor; also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM.

  • CAS Number: 65271-80-9
  • MF: C22H28N4O6
  • MW: 444.481
  • Catalog: Topoisomerase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 805.7±65.0 °C at 760 mmHg
  • Melting Point: 170-174ºC
  • Flash Point: 441.1±34.3 °C

THK01

THK01 is a potent ROCK2 inhibitor with IC50 values of 5.7 and 923 nM for ROCK2 and ROCK1, respectively. THK01 inhibits breast cancer metastasis through the ROCK2-STAT3 signaling pathway. THK01 can be used in research of breast cancer[1].

  • CAS Number: 2226941-26-8
  • MF: C20H13N3O2
  • MW: 327.34
  • 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

PF-4950834

PF-4950834 is a potent, selective, orally bioavailable, ATP-competitive rho kinase inhibitor with IC50 values of 8.35 nM and 33.12 nM against ROCK2 and ROCK1, respectively. PF-4950834 inhibits neutrophil migration[1].

  • CAS Number: 1256264-62-6
  • MF: C21H19N3O2
  • MW: 345.39
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TX-1123

TX-1123 is a potent protein tyrosine kinase (PTK) inhibitor for Src, eEF2-K, and PKA, and EGFR-K/PKC. TX-1123 is a cyclo-oxygenase (COX) inhibitor with IC50 values of 1.16 μM and 15.7 μM for COX2 and COX1, respectively. TX-1123 has low mitochondrial toxicity. TX-1123 can be used in research of cancer[1][2].

  • CAS Number: 157397-06-3
  • MF: C20H24O3
  • MW: 312.40300
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A