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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Protein Kinase C (19-31)

Protein Kinase C (19-31), a peptide inhibitor of protein kinase C (PKC), derived from the pseudo-substrate regulatory domain of PKCa (residues 19-31) with a serine at position 25 replacing the wild-type alanine, is used as protein kinase C substrate peptide for testing the protein kinase C activity. Protein kinase C (PKC) is involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins[1][2].

  • CAS Number: 121545-65-1
  • MF: C67H118N26O16
  • MW: 1543.82
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

12-O-tetradecanoylphorbol-13-acetate

Phorbol 12-myristate 13-acetate (PMA), a phorbol ester, is a commonly used PKC activator.

  • CAS Number: 16561-29-8
  • MF: C36H56O8
  • MW: 616.825
  • Catalog: PKC
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 698.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 208.1±25.0 °C

DHAQ DIACETATE

Mitoxantrone diacetate is a potent topoisomerase II inhibitor. Mitoxantrone diacetate also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM. Mitoxantrone diacetate induces apoptosis of B-CLL (B-chronic lymphocytic leukaemia) cells. Mitoxantrone diacetate shows antitumor activity[1][2][3][4]. Mitoxantrone diacetate also has anti-orthopoxvirus activity with EC50s of 0.25 μM and and 0.8 μM for cowpox and monkeypox, respectively[5].

  • CAS Number: 70711-41-0
  • MF: C24H32N4O8
  • MW: 504.53300
  • Catalog: Apoptosis
  • Density: 1.45g/cm3
  • Boiling Point: 805.7ºC at 760 mmHg
  • Melting Point: 203-5ºC
  • Flash Point: 441.1ºC

Valrubicin

Valrubicin is a chemotherapy agent, inhibits TPA- and PDBu-induced PKC activation with IC50s of 0.85 and 1.25 μM, respectively, and has antitumor and antiinflammatory activity.

  • CAS Number: 56124-62-0
  • MF: C34H36F3NO13
  • MW: 723.644
  • Catalog: PKC
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 867.7±65.0 °C at 760 mmHg
  • Melting Point: 116-117ºC
  • Flash Point: 478.6±34.3 °C

Pirfenidone D5

Pirfenidone D5 (AMR69 D5) is a deuterium labeled Pirfenidone. Pirfenidone is an antifibrotic agent that attenuates CCL2 and CCL12 production in fibrocyte cells. Pirfenidone has growth-inhibitory effect and reduces TGF-β2 protein levels in human glioma cell lines. Pirfenidone also has anti-inflammatory activities[1][2][3].

  • CAS Number: 1020719-62-3
  • MF: C12H6D5NO
  • MW: 190.25300
  • Catalog: CCR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dalbergioidin

Dalbergioidin, a well-known anthocyanin, ameliorates doxorubicin-induced renal fibrosis by suppressing the TGF-β signal pathway. Dalbergioidin exhibits tyrosinase inhibitory activity with an IC50 of 20 mM[1][2].

  • CAS Number: 30368-42-4
  • MF: C15H12O6
  • MW: 288.25
  • Catalog: TGF-beta/Smad
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 631.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 244.4±25.0 °C

Nisevokitug

Nisevokitug (NIS-793) is a human, IgG2λ antibody targeting TGF-β (TGFB1/TGFB2). Nisevokitug is expressed by CHO-K1 cells[1].

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

DT-6

DT-6 is an effective TGF-β1 inhibitor. DT-6 inhibits M2 macrophage induced epithelial to mesenchymal transition and invasive migration of cancer cells. DT-6 can be used for cancer diseases research[1].

  • CAS Number: 2414315-95-8
  • MF: C89H130N20O29S2
  • MW: 2008.23
  • Catalog: TGF-beta/Smad
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sotrastaurin

Sotrastaurin is a potent pan-PKC inhibitor, with Kis of 0.22 nM, 0.64nM, 0.95 nM, 1.8 nM, 2.1 nM and 3.2 nM for PKCθ, PKCβ, PKCα, PKCη, PKCδ and PKCε, respectively.

  • CAS Number: 425637-18-9
  • MF: C25H22N6O2
  • MW: 438.481
  • Catalog: PKC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VTX-27

VTX-27 is a selective protein kinase C θ (PKC θ) inhibitor, with Kis of 0.08 nM and 16 nM for PKC θ and PKC δ.

  • CAS Number: 1321924-70-2
  • MF: C20H24ClFN6O
  • MW: 418.896
  • Catalog: PKC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 625.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 332.3±31.5 °C

ZIP

ZIP is a selective peptide inhibitor of PKMζ. ZIP injections can block the impairment in morphine conditioned place preference induced[1].

  • CAS Number: 863987-12-6
  • MF: C12H25N3S4Zn
  • MW: 405.016
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Halofuginone Hydrobromide

Halofuginone hydrobromide (RU-19110 hydrobromide) is a less-toxic form of Febrifugine, which is isolated from the plant Dichroa febrifuga[1]. Halofuginone inhibits prolyl-tRNA synthetase in an ATP-dependent manner with a Ki of 18.3 nM[2]. Halofuginone attenuates osteoarthritis (OA) by inhibition of TGF-β activity[3].

  • CAS Number: 64924-67-0
  • MF: C16H18Br2ClN3O3
  • MW: 495.59300
  • Catalog: DNA/RNA Synthesis
  • Density: N/A
  • Boiling Point: 595.8ºC at 760 mmHg
  • Melting Point: 247° (dec)
  • Flash Point: 314.1ºC

PT-262

PT-262 is a potent ROCK inhibitor with an IC50 value of around 5 μM. PT-262 induces the loss of mitochondrial membrane potential and elevates the caspase-3 activation and apoptosis. PT-262 inhibits the ERK and CDC2 phosphorylation via a p53-independent pathway. PT-262 blocks cytoskeleton function and cell migration. PT-262 has anti-cancer activity[1][2].

  • CAS Number: 86811-36-1
  • MF: C14H13ClN2O2
  • MW: 276.72
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PS-432

PS-432 is an allosteric inhibitor of PKCι and PKCζ with IC50 of 16.9 and 18.5 uM, respectively; has no inhibitory activity against PKCα, PKCβ, PKCδ and PKCθ nor the activity of related kinases such as PDK1, PKB/Akt, RSK1, MSK1 and Aurora A; inhibits the proliferation of the lung cancer cell lines A549 (IC50=14.8 ± 4.2 uM) and A427 (IC50=10.4± 0.3 uM) as well as androgen-independent prostate cancer cell line DU145 (IC50 = 20.8 ± 9.0 uM); well tolerated in vivo.

  • CAS Number: 2083630-26-4
  • MF: C25H19ClN2O5S
  • MW: 494.947
  • Catalog: PKC
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 662.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 354.5±34.3 °C

ROCK-IN-4

ROCK-IN-4 is a potent ROCK inhibitor maintaining NO releasing ability. ROCK-IN-4 reversibly depolymerizes F-actin, and suppresses mitochondrial respiration in human trabecular meshwork (HTM) cells. ROCK-IN-4 can be used for glaucoma or ocular hypertension research[1].

  • CAS Number: 2488395-07-7
  • MF: C20H26ClFN4O7S
  • MW: 520.96
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rho-Kinase-IN-2

Rho-Kinase-IN-2 (Compound 23) is an orally active, selective, and central nervous system (CNS)-penetrant Rho Kinase (ROCK) inhibitor (ROCK2 IC50=3 nM). Rho-Kinase-IN-2 can be used in Huntington’s research[1].

  • CAS Number: 2573071-18-6
  • MF: C20H25FN4O2
  • MW: 372.44
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SIS3

SIS3 is a cell-permeable and selective inhibitor of Smad3. It inhibits Smad3 phosphorylation with an IC50 of 3 µM.

  • CAS Number: 521984-48-5
  • MF: C28H28ClN3O3
  • MW: 489.993
  • Catalog: TGF-beta/Smad
  • Density: N/A
  • Boiling Point: 737.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 399.7ºC

6-Deoxyisojacareubin

6-Deoxyisojacareubin is a PKC inhibitor that inhibits the proliferation of QGY-7703 cells in a concentration-dependent manner. 6-Deoxyisojacareubin is also a natural product that can be obtained from Garcinia nervosa. 6-Deoxyisojacareubin can be used in cancer research[1].

  • CAS Number: 26486-92-0
  • MF: C18H14O5
  • MW: 310.30
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cercosporin

Cercosporin is produced by a plant pathogen, Cercosporakikuchii, and the elsinochromes, pigments of the elsinoe family of fungi. Cercosporin is a potent photosensitizer with a short activation wavelength, mostly suitable for superficial photodynamic therapy (PDT) treatments, especially when it is necessary to avoid perforations[1].Cercosporin contains the perylenequinone structural features necessary to PKC activity with an IC50 of 0.6-1.3 μM[2].

  • CAS Number: 35082-49-6
  • MF: C29H26O10
  • MW: 534.51100
  • Catalog: PKC
  • Density: 1.59g/cm3
  • Boiling Point: 886.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 299ºC

Darovasertib (LXS-196)

LXS196 is a potent and orally active protein kinase C (PKC) inhibitor under Phase I clinical trials for the treatment of uveal melanoma.

  • CAS Number: 1874276-76-2
  • MF: C22H23F3N8O
  • MW: 472.466
  • Catalog: PKC
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 592.7±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 312.3±30.1 °C

Hydroxyfasudil

Hydroxyfasudil is a ROCK inhibitor, with IC50s of 0.73 and 0.72 μM for ROCK1 and ROCK2, respectively.

  • CAS Number: 105628-72-6
  • MF: C14H17N3O3S
  • MW: 307.36800
  • Catalog: ROCK
  • Density: 1.329g/cm3
  • Boiling Point: 613.7ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 325ºC

Isojacareubin

Isojacareubin can be isolated from Hypericum japonicum. Isojacareubin covalently inhibits SARS-CoV-2 3CLpro. Isojacareubin also has anti-helicobacter activity. Isojacareubin inhibits PKC, and suppresses hepatocellular carcinoma metastasis and induces apoptosis[1][2][3].

  • CAS Number: 50597-93-8
  • MF: C18H14O6
  • MW: 326.30
  • Catalog: Bacterial
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 576.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 216.0±23.6 °C

[Ala113] -MBP(104-118)

[Ala113]MBP(104-118) is an noncompetitive peptide inhibitors of protein kinase C (PKC), with IC50s ranging from 28-62 μM[1].

  • CAS Number: 99026-78-5
  • MF: C67H104N20O19
  • MW: 1493.67000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

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

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